TY  - CONF
AU  - Divac Rankov, Aleksandra
AU  - Kušić-Tišma, Jelena
AU  - Đorđević, Valentina
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2177
AB  - Bioinformatics was established at the IMGGE
in collaboration with the Beijing Genomics Institute
(BGI) and with the support of the Government of
the Republic of Serbia. The Center was founded
with the aim of accelerating the implementation
of 4P medicine (Preventive, Predictive, Personalized,
and Participatory), in our country by using the
cutting-edge tools of molecular biology and information
technology. As such, the center is unique in
Serbia and the South East Europe region.
The state-of-the-art equipment existing at the
Center (DNBSEQ-G400 (BGI), NextSeq 550Dx,
2000 and MiSeq (Illumina) Sequencing Systems;
MinION (OxfordNanopore); MGISP-9600
High-throughput Automated Sample Preparation
System) offered a wide range of application: the
whole genome and whole exome sequencing, targeted
sequencing, transcriptome sequencing and
more. The analysis of data was facilitated by the
access to the National Platform for Artificial Intelligence providing space for secure data storage, and
to a supercomputer (Nvidia), critical for processing
and analyzing Big Data.
Since its establishment more than 2000
SARS-CoV2 genomes were sequenced, 300 patient
samples undervent diagnostic work-up. Pilot project
for NIFTYPro screening was finished encompasing
58 pregnant women. First transcriptomes
and metagenomes were analyzed.
Further implementation of NGS methodology
in research and for diagnostics, and intensive
development of bioinformatics, by strengthening
the hardware and software capacities and the education
of the bioinformatics team, will lead us in
becoming driving force of the development of biomedicine
and biotechnology in Serbia, extending
collaboration beyond our borders.
PB  - Macedonian Academy of Sciences and Arts
C3  - International Journal of Medical Genetics
T1  - STRENGTHENING THE NEXT-GENERATION SEQUENCING AND BIOINFORMATICS CAPACITIES IN THE REPUBLIC OF SERBIA
EP  - 75
IS  - Supplement
SP  - 75
VL  - 26
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2177
ER  - 

@conference{
author = "Divac Rankov, Aleksandra and Kušić-Tišma, Jelena and Đorđević, Valentina",
year = "2023",
abstract = "Bioinformatics was established at the IMGGE
in collaboration with the Beijing Genomics Institute
(BGI) and with the support of the Government of
the Republic of Serbia. The Center was founded
with the aim of accelerating the implementation
of 4P medicine (Preventive, Predictive, Personalized,
and Participatory), in our country by using the
cutting-edge tools of molecular biology and information
technology. As such, the center is unique in
Serbia and the South East Europe region.
The state-of-the-art equipment existing at the
Center (DNBSEQ-G400 (BGI), NextSeq 550Dx,
2000 and MiSeq (Illumina) Sequencing Systems;
MinION (OxfordNanopore); MGISP-9600
High-throughput Automated Sample Preparation
System) offered a wide range of application: the
whole genome and whole exome sequencing, targeted
sequencing, transcriptome sequencing and
more. The analysis of data was facilitated by the
access to the National Platform for Artificial Intelligence providing space for secure data storage, and
to a supercomputer (Nvidia), critical for processing
and analyzing Big Data.
Since its establishment more than 2000
SARS-CoV2 genomes were sequenced, 300 patient
samples undervent diagnostic work-up. Pilot project
for NIFTYPro screening was finished encompasing
58 pregnant women. First transcriptomes
and metagenomes were analyzed.
Further implementation of NGS methodology
in research and for diagnostics, and intensive
development of bioinformatics, by strengthening
the hardware and software capacities and the education
of the bioinformatics team, will lead us in
becoming driving force of the development of biomedicine
and biotechnology in Serbia, extending
collaboration beyond our borders.",
publisher = "Macedonian Academy of Sciences and Arts",
journal = "International Journal of Medical Genetics",
title = "STRENGTHENING THE NEXT-GENERATION SEQUENCING AND BIOINFORMATICS CAPACITIES IN THE REPUBLIC OF SERBIA",
pages = "75-75",
number = "Supplement",
volume = "26",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2177"
}

Divac Rankov, A., Kušić-Tišma, J.,& Đorđević, V.. (2023). STRENGTHENING THE NEXT-GENERATION SEQUENCING AND BIOINFORMATICS CAPACITIES IN THE REPUBLIC OF SERBIA. in International Journal of Medical Genetics
Macedonian Academy of Sciences and Arts., 26(Supplement), 75-75.
https://hdl.handle.net/21.15107/rcub_imagine_2177

Divac Rankov A, Kušić-Tišma J, Đorđević V. STRENGTHENING THE NEXT-GENERATION SEQUENCING AND BIOINFORMATICS CAPACITIES IN THE REPUBLIC OF SERBIA. in International Journal of Medical Genetics. 2023;26(Supplement):75-75.
https://hdl.handle.net/21.15107/rcub_imagine_2177 .

Divac Rankov, Aleksandra, Kušić-Tišma, Jelena, Đorđević, Valentina, "STRENGTHENING THE NEXT-GENERATION SEQUENCING AND BIOINFORMATICS CAPACITIES IN THE REPUBLIC OF SERBIA" in International Journal of Medical Genetics, 26, no. Supplement (2023):75-75,
https://hdl.handle.net/21.15107/rcub_imagine_2177 .

TY  - JOUR
AU  - Smederevac, Snežana
AU  - Delgado-Cruzata, Lissette
AU  - Mitrović, Dušanka
AU  - Dinić, Bojana M.
AU  - Bravo, Toni-Ann T.
AU  - Delgado, Maria
AU  - Bugarski Ignjatović, Vojislava
AU  - Sadiković, Selka
AU  - Milovanović, Ilija
AU  - Vučinić, Nataša
AU  - Branovački, Bojan
AU  - Prinz, Mechthild
AU  - Budimlija, Zoran
AU  - Kušić‐Tišma, Jelena
AU  - Nikolašević, Željka
PY  - 2023
UR  - https://www.frontiersin.org/articles/10.3389/fgene.2022.1067276
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1765
AB  - Epigenetic modifications of the membrane bound catechol-O-methyltransferase (MB-COMT) gene may affect the enzymatic degradation of dopamine, and consequently, human behavior. This study investigated the association between membrane bound catechol-O-methyltransferase DNA methylation (DNAm) differences in 92 monozygotic (MZ) twins with phenotypic manifestations of cognitive, behavioral, and personality indicators associated with reward-related behaviors and lack of control. We used pyrosequencing to determine DNAm of the regulatory region of membrane bound catechol-O-methyltransferase in saliva DNA. Results of intrapair differences in the percentage of membrane bound catechol-O-methyltransferase DNAm at each of five CpG sites show that there are associations between phenotypic indicators of lack of control and membrane bound catechol-O-methyltransferase DNAm differences on CpG1, CpG2 and CpG4, suggesting the common epigenetic patterns for personality traits, cognitive functions, and risk behaviors.
T2  - Frontiers in Genetics
T2  - Frontiers in Genetics
T1  - Differences in MB-COMT DNA methylation in monozygotic twins on phenotypic indicators of impulsivity
VL  - 13
DO  - 10.3389/fgene.2022.1067276
ER  - 

@article{
author = "Smederevac, Snežana and Delgado-Cruzata, Lissette and Mitrović, Dušanka and Dinić, Bojana M. and Bravo, Toni-Ann T. and Delgado, Maria and Bugarski Ignjatović, Vojislava and Sadiković, Selka and Milovanović, Ilija and Vučinić, Nataša and Branovački, Bojan and Prinz, Mechthild and Budimlija, Zoran and Kušić‐Tišma, Jelena and Nikolašević, Željka",
year = "2023",
abstract = "Epigenetic modifications of the membrane bound catechol-O-methyltransferase (MB-COMT) gene may affect the enzymatic degradation of dopamine, and consequently, human behavior. This study investigated the association between membrane bound catechol-O-methyltransferase DNA methylation (DNAm) differences in 92 monozygotic (MZ) twins with phenotypic manifestations of cognitive, behavioral, and personality indicators associated with reward-related behaviors and lack of control. We used pyrosequencing to determine DNAm of the regulatory region of membrane bound catechol-O-methyltransferase in saliva DNA. Results of intrapair differences in the percentage of membrane bound catechol-O-methyltransferase DNAm at each of five CpG sites show that there are associations between phenotypic indicators of lack of control and membrane bound catechol-O-methyltransferase DNAm differences on CpG1, CpG2 and CpG4, suggesting the common epigenetic patterns for personality traits, cognitive functions, and risk behaviors.",
journal = "Frontiers in Genetics, Frontiers in Genetics",
title = "Differences in MB-COMT DNA methylation in monozygotic twins on phenotypic indicators of impulsivity",
volume = "13",
doi = "10.3389/fgene.2022.1067276"
}

Smederevac, S., Delgado-Cruzata, L., Mitrović, D., Dinić, B. M., Bravo, T. T., Delgado, M., Bugarski Ignjatović, V., Sadiković, S., Milovanović, I., Vučinić, N., Branovački, B., Prinz, M., Budimlija, Z., Kušić‐Tišma, J.,& Nikolašević, Ž.. (2023). Differences in MB-COMT DNA methylation in monozygotic twins on phenotypic indicators of impulsivity. in Frontiers in Genetics, 13.
https://doi.org/10.3389/fgene.2022.1067276

Smederevac S, Delgado-Cruzata L, Mitrović D, Dinić BM, Bravo TT, Delgado M, Bugarski Ignjatović V, Sadiković S, Milovanović I, Vučinić N, Branovački B, Prinz M, Budimlija Z, Kušić‐Tišma J, Nikolašević Ž. Differences in MB-COMT DNA methylation in monozygotic twins on phenotypic indicators of impulsivity. in Frontiers in Genetics. 2023;13.
doi:10.3389/fgene.2022.1067276 .

Smederevac, Snežana, Delgado-Cruzata, Lissette, Mitrović, Dušanka, Dinić, Bojana M., Bravo, Toni-Ann T., Delgado, Maria, Bugarski Ignjatović, Vojislava, Sadiković, Selka, Milovanović, Ilija, Vučinić, Nataša, Branovački, Bojan, Prinz, Mechthild, Budimlija, Zoran, Kušić‐Tišma, Jelena, Nikolašević, Željka, "Differences in MB-COMT DNA methylation in monozygotic twins on phenotypic indicators of impulsivity" in Frontiers in Genetics, 13 (2023),
https://doi.org/10.3389/fgene.2022.1067276 . .

TY  - CONF
AU  - Drakulić, Danijela
AU  - Rakonjac, Marijana
AU  - Cuturilo, Goran
AU  - Kovačević-Grujičić, Nataša
AU  - Kušić-Tišma, Jelena
AU  - Morić, Ivana
AU  - Zukić, Branka
AU  - Stevanović, Milena
PY  - 2023
UR  - https://belbi.bg.ac.rs/
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2036
AB  - 22q11.2 deletion syndrome (22q11.2DS is caused by 22q11.2 microdeletion, one of
the strongest known risk factors for development of neurodevelopmental disorders.
About 70% patients with 22q11.2DS have speech and language impairments. In the
literature, there is no data about articulatory characteristics of phonemes of children
with 22q11.2DS, monolingual native speakers of South Slavic languages. Here we, by
applying Global Articulation Test, analyzed articulatory characteristics of phonemes of
children with 22q11.2DS, monolingual native speakers of the Serbian language (group
E1), children with a phenotype resembling 22q11.2DS but without the microdeletion
(group E2), children with non-syndromic congenital heart malformations (since children
with these malformations may exhibit a speech and language impairments) (group
E3) and their peers with typical speech-sound development (group C). Results of PCA
indicated that the groups can be distinguished based on the pronunciation of phonemes,
and that the pronunciation of the phonemes “Č ⟨tʃ⟩”, “Dž ⟨ʤ⟩”, “Š ⟨∫⟩”, “Ž ⟨ʒ⟩”, “R”, and “Lj ⟨ʎ⟩”
contributes the most to the variability between the groups. Results of AHP revealed that
the pronunciation of the phonemes “Č ⟨tʃ⟩”, “Dž ⟨ʤ⟩”, “Š ⟨∫⟩”, “Ž ⟨ʒ⟩”, “R”, and “Lj ⟨ʎ⟩” was
rated the worst in the group E1. In conclusion, obtained results indicate that the presence
of 22q11.2 microdeletion influences articulation skills of carriers.
PB  - Belgrade : Institute of molecular genetics and genetic engineering
C3  - 4th Belgrade Bioinformatics Conference
T1  - Application of principal component analysis (PCA) and analytical hierarchy process (AHP) in analysis of articulatory characteristics of phonemes of children with 22q11.2 Deletion Syndrome
EP  - 91
SP  - 91
VL  - 4
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2036
ER  - 

@conference{
author = "Drakulić, Danijela and Rakonjac, Marijana and Cuturilo, Goran and Kovačević-Grujičić, Nataša and Kušić-Tišma, Jelena and Morić, Ivana and Zukić, Branka and Stevanović, Milena",
year = "2023",
abstract = "22q11.2 deletion syndrome (22q11.2DS is caused by 22q11.2 microdeletion, one of
the strongest known risk factors for development of neurodevelopmental disorders.
About 70% patients with 22q11.2DS have speech and language impairments. In the
literature, there is no data about articulatory characteristics of phonemes of children
with 22q11.2DS, monolingual native speakers of South Slavic languages. Here we, by
applying Global Articulation Test, analyzed articulatory characteristics of phonemes of
children with 22q11.2DS, monolingual native speakers of the Serbian language (group
E1), children with a phenotype resembling 22q11.2DS but without the microdeletion
(group E2), children with non-syndromic congenital heart malformations (since children
with these malformations may exhibit a speech and language impairments) (group
E3) and their peers with typical speech-sound development (group C). Results of PCA
indicated that the groups can be distinguished based on the pronunciation of phonemes,
and that the pronunciation of the phonemes “Č ⟨tʃ⟩”, “Dž ⟨ʤ⟩”, “Š ⟨∫⟩”, “Ž ⟨ʒ⟩”, “R”, and “Lj ⟨ʎ⟩”
contributes the most to the variability between the groups. Results of AHP revealed that
the pronunciation of the phonemes “Č ⟨tʃ⟩”, “Dž ⟨ʤ⟩”, “Š ⟨∫⟩”, “Ž ⟨ʒ⟩”, “R”, and “Lj ⟨ʎ⟩” was
rated the worst in the group E1. In conclusion, obtained results indicate that the presence
of 22q11.2 microdeletion influences articulation skills of carriers.",
publisher = "Belgrade : Institute of molecular genetics and genetic engineering",
journal = "4th Belgrade Bioinformatics Conference",
title = "Application of principal component analysis (PCA) and analytical hierarchy process (AHP) in analysis of articulatory characteristics of phonemes of children with 22q11.2 Deletion Syndrome",
pages = "91-91",
volume = "4",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2036"
}

Drakulić, D., Rakonjac, M., Cuturilo, G., Kovačević-Grujičić, N., Kušić-Tišma, J., Morić, I., Zukić, B.,& Stevanović, M.. (2023). Application of principal component analysis (PCA) and analytical hierarchy process (AHP) in analysis of articulatory characteristics of phonemes of children with 22q11.2 Deletion Syndrome. in 4th Belgrade Bioinformatics Conference
Belgrade : Institute of molecular genetics and genetic engineering., 4, 91-91.
https://hdl.handle.net/21.15107/rcub_imagine_2036

Drakulić D, Rakonjac M, Cuturilo G, Kovačević-Grujičić N, Kušić-Tišma J, Morić I, Zukić B, Stevanović M. Application of principal component analysis (PCA) and analytical hierarchy process (AHP) in analysis of articulatory characteristics of phonemes of children with 22q11.2 Deletion Syndrome. in 4th Belgrade Bioinformatics Conference. 2023;4:91-91.
https://hdl.handle.net/21.15107/rcub_imagine_2036 .

Drakulić, Danijela, Rakonjac, Marijana, Cuturilo, Goran, Kovačević-Grujičić, Nataša, Kušić-Tišma, Jelena, Morić, Ivana, Zukić, Branka, Stevanović, Milena, "Application of principal component analysis (PCA) and analytical hierarchy process (AHP) in analysis of articulatory characteristics of phonemes of children with 22q11.2 Deletion Syndrome" in 4th Belgrade Bioinformatics Conference, 4 (2023):91-91,
https://hdl.handle.net/21.15107/rcub_imagine_2036 .

TY  - JOUR
AU  - Bačić, Jasmina
AU  - Bosnić, Dragana
AU  - Samardžić, Jelena
AU  - Avdalović, Radmila
AU  - Mickovski-Stefanović, Violeta
AU  - Kušić-Tišma, Jelena
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1543
AB  - Korenove nematode ili nematode korenovih gala mogu prouzrokovati značajne gubitke u prinosu krompira u toplim i hladnim regionima. Šest vrsta Meloidogine mogu parazitirati krompir. Vrste Meloidogyne chitvoodi, M. fallax i M. hapla prisutne su u hladnim regionima, dok su M. arenaria, M. incognita i M. javanica uobičajene u toplim regionima i pripadaju tropskoj grupi Meloidogyne vrsta. Meloidogyne arenaria je prisutna u regionima sa kontinentalnom klimom u zaštićenom prostoru i napada veliki broj biljaka domaćina. U oktobru 2018. primećen je usev krompira var. Balatonska ruža sa tumoroznim izraslinama na 70% krtola tokom posebnog nadzora karantinskih vrsta nematoda Meloidogyne chitvoodi i M. fallax na lokalitetu Horgoš, opština Kanjiža, Pokrajina Vojvodina. Uočeni su i simptomi usporenog rasta i uvenuća biljaka. Ženke su korišćene za morfološku i molekularnu identifikaciju. Morfološka analiza vulvalno-analnih konusa je utvrdila vrstu M. arenaria. Identifikacija vrste je potvrđena molekularnom analizom korišćenjem grupnih specifičnih prajmera u rDNK regionu i SCAR prajmera specifičnih za identifikaciju vrste M. arenaria. Prema našim saznanjima, ovo je prvi nalaz velike štetnosti na krompiru prouzrokovanim prisustvom M. arenaria u polju u Srbiji. Na delu Balkanskog poluostrva sa kontinentalnom klimom nisu ranije zabeležene velike štete usled prisustva M. arenaria na krompiru na otvorenom. Ova tropska vrsta Meloidogyne mogla bi u budućnosti da postane novi fitosanitarni problem u Evropi usled globalnog zagrevanja i klimatskih promena.
AB  - Root-knot nematodes can cause significant losses in potato yield in warm and cool regions. Six Meloidogyne species can attack potato. Species Meloidogyne chitwoodi, M. fallax, M. hapla, are present in cool regions, while M. arenaria, M. incognita and M. javanica are common in warm regions and considered to belong to the Meloidogyne tropical group. Meloidogyne arenaria is present in regions with continental climate in glasshouses attacking a large number of host-plants. In October 2018, potato crop var. Balathon Rose with galls on 70% of all tubers was noticed during quarantine nematode species Meloidogyne chitwoodi and M. fallax survey in the locality Horgoš, municipality of Kanjiža, Vojvodina Province. Symptoms of stunted and wilted plants were detected as well. Females were used for morphological and molecular identification. Morphological identification of species based on females' perineal patterns indicated the sample as M. arenaria. Species identification was confirmed by molecular analyses using group-specific primers in the rDNA region and species-specific SCAR primers for M. arenaria species identification. To our knowledge, this is the first record of highly damaged potato crop caused by M. arenaria in the field in Serbia. The severity of the damage M. arenaria can cause to potato in the open field has not been observed in the part of Balkan peninsula with continental climate before. This tropical Meloidogyne species may become an emerging phytosanitary problem within Europe in the future due global warming and climate change.
PB  - Institut za ratarstvo i povrtarstvo, Novi Sad
T2  - Ratarstvo i Povrtarstvo
T1  - Prisustvo korenove nematode Meloidogyne arenaria na krompiru u polju u Srbiji
T1  - Occurrence of root-knot nematode Meloidogyne arenaria in the potato field in Serbia
EP  - 55
IS  - 2
SP  - 51
VL  - 59
DO  - 10.5937/ratpov59-38187
ER  - 

@article{
author = "Bačić, Jasmina and Bosnić, Dragana and Samardžić, Jelena and Avdalović, Radmila and Mickovski-Stefanović, Violeta and Kušić-Tišma, Jelena",
year = "2022",
abstract = "Korenove nematode ili nematode korenovih gala mogu prouzrokovati značajne gubitke u prinosu krompira u toplim i hladnim regionima. Šest vrsta Meloidogine mogu parazitirati krompir. Vrste Meloidogyne chitvoodi, M. fallax i M. hapla prisutne su u hladnim regionima, dok su M. arenaria, M. incognita i M. javanica uobičajene u toplim regionima i pripadaju tropskoj grupi Meloidogyne vrsta. Meloidogyne arenaria je prisutna u regionima sa kontinentalnom klimom u zaštićenom prostoru i napada veliki broj biljaka domaćina. U oktobru 2018. primećen je usev krompira var. Balatonska ruža sa tumoroznim izraslinama na 70% krtola tokom posebnog nadzora karantinskih vrsta nematoda Meloidogyne chitvoodi i M. fallax na lokalitetu Horgoš, opština Kanjiža, Pokrajina Vojvodina. Uočeni su i simptomi usporenog rasta i uvenuća biljaka. Ženke su korišćene za morfološku i molekularnu identifikaciju. Morfološka analiza vulvalno-analnih konusa je utvrdila vrstu M. arenaria. Identifikacija vrste je potvrđena molekularnom analizom korišćenjem grupnih specifičnih prajmera u rDNK regionu i SCAR prajmera specifičnih za identifikaciju vrste M. arenaria. Prema našim saznanjima, ovo je prvi nalaz velike štetnosti na krompiru prouzrokovanim prisustvom M. arenaria u polju u Srbiji. Na delu Balkanskog poluostrva sa kontinentalnom klimom nisu ranije zabeležene velike štete usled prisustva M. arenaria na krompiru na otvorenom. Ova tropska vrsta Meloidogyne mogla bi u budućnosti da postane novi fitosanitarni problem u Evropi usled globalnog zagrevanja i klimatskih promena., Root-knot nematodes can cause significant losses in potato yield in warm and cool regions. Six Meloidogyne species can attack potato. Species Meloidogyne chitwoodi, M. fallax, M. hapla, are present in cool regions, while M. arenaria, M. incognita and M. javanica are common in warm regions and considered to belong to the Meloidogyne tropical group. Meloidogyne arenaria is present in regions with continental climate in glasshouses attacking a large number of host-plants. In October 2018, potato crop var. Balathon Rose with galls on 70% of all tubers was noticed during quarantine nematode species Meloidogyne chitwoodi and M. fallax survey in the locality Horgoš, municipality of Kanjiža, Vojvodina Province. Symptoms of stunted and wilted plants were detected as well. Females were used for morphological and molecular identification. Morphological identification of species based on females' perineal patterns indicated the sample as M. arenaria. Species identification was confirmed by molecular analyses using group-specific primers in the rDNA region and species-specific SCAR primers for M. arenaria species identification. To our knowledge, this is the first record of highly damaged potato crop caused by M. arenaria in the field in Serbia. The severity of the damage M. arenaria can cause to potato in the open field has not been observed in the part of Balkan peninsula with continental climate before. This tropical Meloidogyne species may become an emerging phytosanitary problem within Europe in the future due global warming and climate change.",
publisher = "Institut za ratarstvo i povrtarstvo, Novi Sad",
journal = "Ratarstvo i Povrtarstvo",
title = "Prisustvo korenove nematode Meloidogyne arenaria na krompiru u polju u Srbiji, Occurrence of root-knot nematode Meloidogyne arenaria in the potato field in Serbia",
pages = "55-51",
number = "2",
volume = "59",
doi = "10.5937/ratpov59-38187"
}

Bačić, J., Bosnić, D., Samardžić, J., Avdalović, R., Mickovski-Stefanović, V.,& Kušić-Tišma, J.. (2022). Prisustvo korenove nematode Meloidogyne arenaria na krompiru u polju u Srbiji. in Ratarstvo i Povrtarstvo
Institut za ratarstvo i povrtarstvo, Novi Sad., 59(2), 51-55.
https://doi.org/10.5937/ratpov59-38187

Bačić J, Bosnić D, Samardžić J, Avdalović R, Mickovski-Stefanović V, Kušić-Tišma J. Prisustvo korenove nematode Meloidogyne arenaria na krompiru u polju u Srbiji. in Ratarstvo i Povrtarstvo. 2022;59(2):51-55.
doi:10.5937/ratpov59-38187 .

Bačić, Jasmina, Bosnić, Dragana, Samardžić, Jelena, Avdalović, Radmila, Mickovski-Stefanović, Violeta, Kušić-Tišma, Jelena, "Prisustvo korenove nematode Meloidogyne arenaria na krompiru u polju u Srbiji" in Ratarstvo i Povrtarstvo, 59, no. 2 (2022):51-55,
https://doi.org/10.5937/ratpov59-38187 . .

TY  - CONF
AU  - Bačković, Dragana
AU  - Novković, Mirjana
AU  - Matić, Dragan
AU  - Antonijević, Nebojša
AU  - Strugarević, Evgenija
AU  - Kovač, Mirjana
AU  - Kušić-Tišma, Jelena
AU  - Rakićević, Ljiljana
AU  - Radojković, Dragica
PY  - 2021
UR  - https://www.uksrb.rs/en/magazine/archive/heart-and-blood-vessels-number-32021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2344
AB  - Introduction. Despite proven clinical effect of clopidogrel, a
considerable number of patients do not have an adequate
response to this type of medication. Problems during therapy occur in the form of resistance, which is present in 11%
of patients or bleeding that occurs in about 9% of patients.
Pharmacogenomics studies demonstrated that variants of
the CYP2C19 gene significantly influence the interindividual heterogenity of the clopidogrel response. The American
Heart Association, US Food and Drug Administration and the
European Medicines Agency, cite the CYP2C19 gene as a significant factor which influences patients response to clopidogrel. Further, it has been shown that the contribution of
genetic and non-genetic factors affecting clopidogrel therapy
may vary between patients from different populations, which
justifies conducting population-specific studies.
The aim. The aim of our study was to examine the significance
of the CYP2C19*2 and the CYP2C19*17 variants in the individual response to clopidogrel, in Serbian patients.
Methods. The study involved 108 patients with carotid artery
stenosis who underwent endarterectomy and received clopidogrel for at least 30 days after the intervention. Also, 120
patients with myocardial infarction receiving clopidogrel after PCI (percutaneous coronary intervention) were included.
Commercial tests were used for standard laboratory testing.
Allelic discrimination was performed after Sanger sequencing.
Results were analysed using statistical tests.
Results. In patients undergoing endarterectomy CYP2C19*2
carriers had a higher risk for being clopidogrel low-responder
in comparison with non-carriers (1.250, 95% CI 1.695–1.658,
P<0.01). In the group of patients undergoing PCI, risk for reinfarction in patients who were carriers of CYP2C19*2 was higher
compared to patients with wild type genotype (OR 5.355, 95%
CI 0.955-31.08; P=0.038). Variant CYP2C19*17 showed no association with variations in response to clopidogrel therapy.
Conclusion. The CYP2C19*2 variant shows significant association with a poor response to clopidogrel and it should be
considered when planning therapy.
PB  - Beograd : Udruženje kardiologa Srbije
C3  - Heart and Blood Vessels
T1  - Analysis of the association of the CYP2C19 variants with the effects of clopidogrel therapy in patients underwent to carotid endarterectomy
IS  - 3
VL  - 40
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2344
ER  - 

@conference{
author = "Bačković, Dragana and Novković, Mirjana and Matić, Dragan and Antonijević, Nebojša and Strugarević, Evgenija and Kovač, Mirjana and Kušić-Tišma, Jelena and Rakićević, Ljiljana and Radojković, Dragica",
year = "2021",
abstract = "Introduction. Despite proven clinical effect of clopidogrel, a
considerable number of patients do not have an adequate
response to this type of medication. Problems during therapy occur in the form of resistance, which is present in 11%
of patients or bleeding that occurs in about 9% of patients.
Pharmacogenomics studies demonstrated that variants of
the CYP2C19 gene significantly influence the interindividual heterogenity of the clopidogrel response. The American
Heart Association, US Food and Drug Administration and the
European Medicines Agency, cite the CYP2C19 gene as a significant factor which influences patients response to clopidogrel. Further, it has been shown that the contribution of
genetic and non-genetic factors affecting clopidogrel therapy
may vary between patients from different populations, which
justifies conducting population-specific studies.
The aim. The aim of our study was to examine the significance
of the CYP2C19*2 and the CYP2C19*17 variants in the individual response to clopidogrel, in Serbian patients.
Methods. The study involved 108 patients with carotid artery
stenosis who underwent endarterectomy and received clopidogrel for at least 30 days after the intervention. Also, 120
patients with myocardial infarction receiving clopidogrel after PCI (percutaneous coronary intervention) were included.
Commercial tests were used for standard laboratory testing.
Allelic discrimination was performed after Sanger sequencing.
Results were analysed using statistical tests.
Results. In patients undergoing endarterectomy CYP2C19*2
carriers had a higher risk for being clopidogrel low-responder
in comparison with non-carriers (1.250, 95% CI 1.695–1.658,
P<0.01). In the group of patients undergoing PCI, risk for reinfarction in patients who were carriers of CYP2C19*2 was higher
compared to patients with wild type genotype (OR 5.355, 95%
CI 0.955-31.08; P=0.038). Variant CYP2C19*17 showed no association with variations in response to clopidogrel therapy.
Conclusion. The CYP2C19*2 variant shows significant association with a poor response to clopidogrel and it should be
considered when planning therapy.",
publisher = "Beograd : Udruženje kardiologa Srbije",
journal = "Heart and Blood Vessels",
title = "Analysis of the association of the CYP2C19 variants with the effects of clopidogrel therapy in patients underwent to carotid endarterectomy",
number = "3",
volume = "40",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2344"
}

Bačković, D., Novković, M., Matić, D., Antonijević, N., Strugarević, E., Kovač, M., Kušić-Tišma, J., Rakićević, L.,& Radojković, D.. (2021). Analysis of the association of the CYP2C19 variants with the effects of clopidogrel therapy in patients underwent to carotid endarterectomy. in Heart and Blood Vessels
Beograd : Udruženje kardiologa Srbije., 40(3).
https://hdl.handle.net/21.15107/rcub_imagine_2344

Bačković D, Novković M, Matić D, Antonijević N, Strugarević E, Kovač M, Kušić-Tišma J, Rakićević L, Radojković D. Analysis of the association of the CYP2C19 variants with the effects of clopidogrel therapy in patients underwent to carotid endarterectomy. in Heart and Blood Vessels. 2021;40(3).
https://hdl.handle.net/21.15107/rcub_imagine_2344 .

Bačković, Dragana, Novković, Mirjana, Matić, Dragan, Antonijević, Nebojša, Strugarević, Evgenija, Kovač, Mirjana, Kušić-Tišma, Jelena, Rakićević, Ljiljana, Radojković, Dragica, "Analysis of the association of the CYP2C19 variants with the effects of clopidogrel therapy in patients underwent to carotid endarterectomy" in Heart and Blood Vessels, 40, no. 3 (2021),
https://hdl.handle.net/21.15107/rcub_imagine_2344 .

TY  - JOUR
AU  - Divac Rankov, Aleksandra
AU  - Kušić-Tišma, Jelena
AU  - Ljujić, Mila
AU  - Nikolić, Aleksandra
AU  - Milosević, Katarina
AU  - Dautović, Gordana Vilotijevic
AU  - Radojković, Dragica
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1381
AB  - Background: High heterogeneity levels of cystic fibrosis transmembrane regulator (CFTR) are manifested in different populations. The aim of this study was to analyze comprehensively all mutations in the CFTR gene in Serbian patients with cystic fibrosis (CF) and to use the findings to propose a testing algorithm for the Serbian population. Materials and Methods: Cascade screening was employed to detect mutations in the CFTR gene of 90 patients suspected of having CF, using polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism or PCR-mediated site directed mutagenesis, Sanger sequencing, and/or next-generation sequencing. Results: This is the first report for the Serbian CF population where single nucleotide polymorphisms, small insertions and deletions, large genome rearrangements, and copy number variants were analyzed in detail. A high degree of heterogeneity within the CFTR was documented among our cohort of 90 patients. We identified 19 CF-causing mutations and 3 with varying consequences, including a previously unreported deletion of the entire exon 11. Conclusion: Considering the spectrum and frequency of mutations found, we recommend a multistep sequencing algorithm in combination with evaluation of large rearrangements for future analyses of the CFTR gene in the Serbian population.
PB  - Mary Ann Liebert, Inc, New Rochelle
T2  - Genetic Testing and Molecular Biomarkers
T1  - Molecular Diagnostics of Cystic Fibrosis in Serbia: Our Approach to Meet the Diagnostic Challenges
EP  - 216
IS  - 4
SP  - 212
VL  - 24
DO  - 10.1089/gtmb.2019.0171
ER  - 

@article{
author = "Divac Rankov, Aleksandra and Kušić-Tišma, Jelena and Ljujić, Mila and Nikolić, Aleksandra and Milosević, Katarina and Dautović, Gordana Vilotijevic and Radojković, Dragica",
year = "2020",
abstract = "Background: High heterogeneity levels of cystic fibrosis transmembrane regulator (CFTR) are manifested in different populations. The aim of this study was to analyze comprehensively all mutations in the CFTR gene in Serbian patients with cystic fibrosis (CF) and to use the findings to propose a testing algorithm for the Serbian population. Materials and Methods: Cascade screening was employed to detect mutations in the CFTR gene of 90 patients suspected of having CF, using polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism or PCR-mediated site directed mutagenesis, Sanger sequencing, and/or next-generation sequencing. Results: This is the first report for the Serbian CF population where single nucleotide polymorphisms, small insertions and deletions, large genome rearrangements, and copy number variants were analyzed in detail. A high degree of heterogeneity within the CFTR was documented among our cohort of 90 patients. We identified 19 CF-causing mutations and 3 with varying consequences, including a previously unreported deletion of the entire exon 11. Conclusion: Considering the spectrum and frequency of mutations found, we recommend a multistep sequencing algorithm in combination with evaluation of large rearrangements for future analyses of the CFTR gene in the Serbian population.",
publisher = "Mary Ann Liebert, Inc, New Rochelle",
journal = "Genetic Testing and Molecular Biomarkers",
title = "Molecular Diagnostics of Cystic Fibrosis in Serbia: Our Approach to Meet the Diagnostic Challenges",
pages = "216-212",
number = "4",
volume = "24",
doi = "10.1089/gtmb.2019.0171"
}

Divac Rankov, A., Kušić-Tišma, J., Ljujić, M., Nikolić, A., Milosević, K., Dautović, G. V.,& Radojković, D.. (2020). Molecular Diagnostics of Cystic Fibrosis in Serbia: Our Approach to Meet the Diagnostic Challenges. in Genetic Testing and Molecular Biomarkers
Mary Ann Liebert, Inc, New Rochelle., 24(4), 212-216.
https://doi.org/10.1089/gtmb.2019.0171

Divac Rankov A, Kušić-Tišma J, Ljujić M, Nikolić A, Milosević K, Dautović GV, Radojković D. Molecular Diagnostics of Cystic Fibrosis in Serbia: Our Approach to Meet the Diagnostic Challenges. in Genetic Testing and Molecular Biomarkers. 2020;24(4):212-216.
doi:10.1089/gtmb.2019.0171 .

Divac Rankov, Aleksandra, Kušić-Tišma, Jelena, Ljujić, Mila, Nikolić, Aleksandra, Milosević, Katarina, Dautović, Gordana Vilotijevic, Radojković, Dragica, "Molecular Diagnostics of Cystic Fibrosis in Serbia: Our Approach to Meet the Diagnostic Challenges" in Genetic Testing and Molecular Biomarkers, 24, no. 4 (2020):212-216,
https://doi.org/10.1089/gtmb.2019.0171 . .

TY  - JOUR
AU  - Novković, Mirjana
AU  - Matić, Dragan
AU  - Kušić-Tišma, Jelena
AU  - Antonijević, Nebojša
AU  - Radojković, Dragica
AU  - Rakićević, Ljiljana
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1187
AB  - Bleeding is one of the possible adverse events during clopidogrel therapy. The CYP2C19 gene is the most significant genetic factor which influences response to clopidogrel treatment. We aimed to examine the contribution of the CYP2C19 gene to bleeding occurrence during clopidogrel therapy in Serbian patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). This case-control study included 53 patients who experienced bleeding and 55 patients without bleeding. Bleeding events were defined and classified using the Bleeding Academic Research Consortium (BARC) criteria. All patients were prescribed daily doses of clopidogrel during the 1-year follow-up after PCI. The CYP2C19*17 (c.-806C  gt  T, rs12248560), rs11568732 (c.-889T  gt  G, CYP2C19*20), CYP2C19*2 (c.681G  gt  A; rs4244285) and CYP2C19*3 (c.636G  gt  A; rs4986893) variants were analysed in all 108 patients. Additionally, sequencing of all nine exons, 5'UTR and 3'UTR in the rs11568732 carriers was performed. Association between bleeding (BARC type ae lt yen gt  2) and the CYP2C19*17 variant was not observed [odds ratio (OR), 0.53; 95% confidence interval (CI), 0.2-1.1; p = 0.107). The rs11568732 variant showed significant association with bleeding (OR, 3.7; 95% CI, 1.12-12.44; p = 0.025). Also, we found that the rs11568732 variant appears independently of haplotype CYP2C19*3B, which is contrary to the previous findings. Our results indicate the absence of CYP2C19*17 influence and turn the attention to the potential significance of the rs11568732 variant in terms of adverse effects of clopidogrel. However, it is necessary to conduct an independent conformation study in order to verify this finding. Also, an analysis of the functional implication of the rs11568732 variant is necessary in order to confirm the significance of this variant, both in relation to its influence on gene expression and in relation to its medical significance.
PB  - Springer Heidelberg, Heidelberg
T2  - European Journal of Clinical Pharmacology
T1  - Analysis of the CYP2C19 genotype associated with bleeding in Serbian STEMI patients who have undergone primary PCI and treatment with clopidogrel
EP  - 451
IS  - 4
SP  - 443
VL  - 74
DO  - 10.1007/s00228-017-2401-5
ER  - 

@article{
author = "Novković, Mirjana and Matić, Dragan and Kušić-Tišma, Jelena and Antonijević, Nebojša and Radojković, Dragica and Rakićević, Ljiljana",
year = "2018",
abstract = "Bleeding is one of the possible adverse events during clopidogrel therapy. The CYP2C19 gene is the most significant genetic factor which influences response to clopidogrel treatment. We aimed to examine the contribution of the CYP2C19 gene to bleeding occurrence during clopidogrel therapy in Serbian patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). This case-control study included 53 patients who experienced bleeding and 55 patients without bleeding. Bleeding events were defined and classified using the Bleeding Academic Research Consortium (BARC) criteria. All patients were prescribed daily doses of clopidogrel during the 1-year follow-up after PCI. The CYP2C19*17 (c.-806C  gt  T, rs12248560), rs11568732 (c.-889T  gt  G, CYP2C19*20), CYP2C19*2 (c.681G  gt  A; rs4244285) and CYP2C19*3 (c.636G  gt  A; rs4986893) variants were analysed in all 108 patients. Additionally, sequencing of all nine exons, 5'UTR and 3'UTR in the rs11568732 carriers was performed. Association between bleeding (BARC type ae lt yen gt  2) and the CYP2C19*17 variant was not observed [odds ratio (OR), 0.53; 95% confidence interval (CI), 0.2-1.1; p = 0.107). The rs11568732 variant showed significant association with bleeding (OR, 3.7; 95% CI, 1.12-12.44; p = 0.025). Also, we found that the rs11568732 variant appears independently of haplotype CYP2C19*3B, which is contrary to the previous findings. Our results indicate the absence of CYP2C19*17 influence and turn the attention to the potential significance of the rs11568732 variant in terms of adverse effects of clopidogrel. However, it is necessary to conduct an independent conformation study in order to verify this finding. Also, an analysis of the functional implication of the rs11568732 variant is necessary in order to confirm the significance of this variant, both in relation to its influence on gene expression and in relation to its medical significance.",
publisher = "Springer Heidelberg, Heidelberg",
journal = "European Journal of Clinical Pharmacology",
title = "Analysis of the CYP2C19 genotype associated with bleeding in Serbian STEMI patients who have undergone primary PCI and treatment with clopidogrel",
pages = "451-443",
number = "4",
volume = "74",
doi = "10.1007/s00228-017-2401-5"
}

Novković, M., Matić, D., Kušić-Tišma, J., Antonijević, N., Radojković, D.,& Rakićević, L.. (2018). Analysis of the CYP2C19 genotype associated with bleeding in Serbian STEMI patients who have undergone primary PCI and treatment with clopidogrel. in European Journal of Clinical Pharmacology
Springer Heidelberg, Heidelberg., 74(4), 443-451.
https://doi.org/10.1007/s00228-017-2401-5

Novković M, Matić D, Kušić-Tišma J, Antonijević N, Radojković D, Rakićević L. Analysis of the CYP2C19 genotype associated with bleeding in Serbian STEMI patients who have undergone primary PCI and treatment with clopidogrel. in European Journal of Clinical Pharmacology. 2018;74(4):443-451.
doi:10.1007/s00228-017-2401-5 .

Novković, Mirjana, Matić, Dragan, Kušić-Tišma, Jelena, Antonijević, Nebojša, Radojković, Dragica, Rakićević, Ljiljana, "Analysis of the CYP2C19 genotype associated with bleeding in Serbian STEMI patients who have undergone primary PCI and treatment with clopidogrel" in European Journal of Clinical Pharmacology, 74, no. 4 (2018):443-451,
https://doi.org/10.1007/s00228-017-2401-5 . .

TY  - JOUR
AU  - Bačković, Dragana
AU  - Ignjatović, Svetlana
AU  - Rakićević, Ljiljana
AU  - Kušić-Tišma, Jelena
AU  - Radojković, Dragica
AU  - Ćalija, Branko
AU  - Strugarević, Evgenija
AU  - Radak, Đorđe
AU  - Kovač, Mirjana
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/988
AB  - Uvod: I pored dokazanog kliničkog efekta oralne antiagregacijske terapije, značajan broj pacijenata nema adekvatan odgovor na primenjeni klopidogrel. Cilj naše studije je bio da se utvrdi uticaj prisutne CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod pacijenata sa stenozom karotidne arterije. Metode: U jednogodišnju prospektivnu studiju uključeno je 112 pacijenata sa stenozom karotidne arterije kod kojih je izvršena endarterektomija. Posle operativnog zahvata, pacijenti su primali 75 mg dnevno klopidogrela u trajanju od najmanje mesec dana. Svi ispitanici su praćeni od momenta prijema. Za CYP2C19 genotipizaciju korišćen je TaqMan test. Uticaj CYP2C19*2 alela na trombocitnu reaktivnost ispitivan je primenom multiple-electrode aggregometry (MEA). Rezultati: Rezultati genotipizacije su pokazali da su 82 (73,2%) ispitanika homozigoti za wild-type, 29 (25,9%) heterozigoti za CYP2C19*2 alel, dok je 1 (0,9%) bio homozigot za CYP2C19*2. Nakon 24 sata, u grupi sa wild-type genotipom 29,3% ispitanika dali su odgovor na klopidogrel, a u grupi sa CYP2C19*2 varijantom gena 10% ispitanika. U grupi sa wild-type genotipom, 74,4% ispitanika su imali terapijski odgovor nakon 7 dana, odnosno 82,9% nakon 30 dana od primene klopidogrela. U grupi sa CYP2C19*2 alelom broj ispitanika sa terapijskim odgovorom raste do 46,7% nakon 7 dana, odnosno do 53,3% nakon 30 dana od primene klopidogrela. Rizik za slab odgovor je veći kod nosilaca CYP2C19*2 alela u odnosu na nenosioce (wild-type) (OR 4,250, 95% CI 1 .695 -10.658 , P lt  0,01). Zaključak: CYP2C19*2 varijanta gena značajno utiče na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije kod kojih je izvršena endarterektomija.
AB  - Background: Despite the proven clinical effect of oral antiplatelet drugs, a considerable number of patients do not have an adequate response to clopidogrel. The aim of our study was to determine the influence of CYP2C19*2 loss-of-function variant allele on clopidogrel responsiveness in patients with carotid artery stenosis. Methods: One hundred and twelve patients with carotid artery stenosis undergoing endarterectomy were included in this one-year prospective study. All of them received clopidogrel (75 mg daily) for at least 30 days after the intervention. They were followed from the moment of hospital admission. CYP2C19*2 genotyping was performed by TaqMan Assay. The influence of c Yp 2C 19*2 variant allele on clopidogrel platelet reactivity was determined using multiple-electrode aggregometry (MEA). Results: Genotyping results showed that 82 (73.2% ) patients were homozygous for wild type, 29 (25.9%) were heterozygous for the CYP2C19*2 allele and 1 (0.9%) was CYP2C19*2 homozygous. After 24 hours, among those with the wild type 29.3% were clopidogrel responders, and in those with the CYP2C19*2 alleles 10%. In the wild type group, 74.4% were clopidogrel responders after 7 days of taking the drug; 82.9% after 30 days of clopidogrel introduction, respectively. In patients with the CYP2C19*2 alleles the number of responders increased up to 46.7% after 7 days; 53.3% after 30 days of taking the drug, respectively. The risk for being a low-responder is higher for the patients heterozygous for the c Yp 2C 19*2 allele vs. wildtype (OR 4.250, 95% CI 1.695 -10.658 , P lt  0.01). Conclusions: The CYP2C19*2 loss-of-function variant allele has significant influence on clopidogrel response in patients with carotid artery stenosis undergoing endarterectomy.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Uticaj CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije
T1  - Influence of CYP2C19*2 gene variant on therapeutic response during clopidogrel treatment in patients with carotid artery stenosis
EP  - 33
IS  - 1
SP  - 26
VL  - 35
DO  - 10.1515/jomb-2015-0009
ER  - 

@article{
author = "Bačković, Dragana and Ignjatović, Svetlana and Rakićević, Ljiljana and Kušić-Tišma, Jelena and Radojković, Dragica and Ćalija, Branko and Strugarević, Evgenija and Radak, Đorđe and Kovač, Mirjana",
year = "2016",
abstract = "Uvod: I pored dokazanog kliničkog efekta oralne antiagregacijske terapije, značajan broj pacijenata nema adekvatan odgovor na primenjeni klopidogrel. Cilj naše studije je bio da se utvrdi uticaj prisutne CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod pacijenata sa stenozom karotidne arterije. Metode: U jednogodišnju prospektivnu studiju uključeno je 112 pacijenata sa stenozom karotidne arterije kod kojih je izvršena endarterektomija. Posle operativnog zahvata, pacijenti su primali 75 mg dnevno klopidogrela u trajanju od najmanje mesec dana. Svi ispitanici su praćeni od momenta prijema. Za CYP2C19 genotipizaciju korišćen je TaqMan test. Uticaj CYP2C19*2 alela na trombocitnu reaktivnost ispitivan je primenom multiple-electrode aggregometry (MEA). Rezultati: Rezultati genotipizacije su pokazali da su 82 (73,2%) ispitanika homozigoti za wild-type, 29 (25,9%) heterozigoti za CYP2C19*2 alel, dok je 1 (0,9%) bio homozigot za CYP2C19*2. Nakon 24 sata, u grupi sa wild-type genotipom 29,3% ispitanika dali su odgovor na klopidogrel, a u grupi sa CYP2C19*2 varijantom gena 10% ispitanika. U grupi sa wild-type genotipom, 74,4% ispitanika su imali terapijski odgovor nakon 7 dana, odnosno 82,9% nakon 30 dana od primene klopidogrela. U grupi sa CYP2C19*2 alelom broj ispitanika sa terapijskim odgovorom raste do 46,7% nakon 7 dana, odnosno do 53,3% nakon 30 dana od primene klopidogrela. Rizik za slab odgovor je veći kod nosilaca CYP2C19*2 alela u odnosu na nenosioce (wild-type) (OR 4,250, 95% CI 1 .695 -10.658 , P lt  0,01). Zaključak: CYP2C19*2 varijanta gena značajno utiče na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije kod kojih je izvršena endarterektomija., Background: Despite the proven clinical effect of oral antiplatelet drugs, a considerable number of patients do not have an adequate response to clopidogrel. The aim of our study was to determine the influence of CYP2C19*2 loss-of-function variant allele on clopidogrel responsiveness in patients with carotid artery stenosis. Methods: One hundred and twelve patients with carotid artery stenosis undergoing endarterectomy were included in this one-year prospective study. All of them received clopidogrel (75 mg daily) for at least 30 days after the intervention. They were followed from the moment of hospital admission. CYP2C19*2 genotyping was performed by TaqMan Assay. The influence of c Yp 2C 19*2 variant allele on clopidogrel platelet reactivity was determined using multiple-electrode aggregometry (MEA). Results: Genotyping results showed that 82 (73.2% ) patients were homozygous for wild type, 29 (25.9%) were heterozygous for the CYP2C19*2 allele and 1 (0.9%) was CYP2C19*2 homozygous. After 24 hours, among those with the wild type 29.3% were clopidogrel responders, and in those with the CYP2C19*2 alleles 10%. In the wild type group, 74.4% were clopidogrel responders after 7 days of taking the drug; 82.9% after 30 days of clopidogrel introduction, respectively. In patients with the CYP2C19*2 alleles the number of responders increased up to 46.7% after 7 days; 53.3% after 30 days of taking the drug, respectively. The risk for being a low-responder is higher for the patients heterozygous for the c Yp 2C 19*2 allele vs. wildtype (OR 4.250, 95% CI 1.695 -10.658 , P lt  0.01). Conclusions: The CYP2C19*2 loss-of-function variant allele has significant influence on clopidogrel response in patients with carotid artery stenosis undergoing endarterectomy.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Uticaj CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije, Influence of CYP2C19*2 gene variant on therapeutic response during clopidogrel treatment in patients with carotid artery stenosis",
pages = "33-26",
number = "1",
volume = "35",
doi = "10.1515/jomb-2015-0009"
}

Bačković, D., Ignjatović, S., Rakićević, L., Kušić-Tišma, J., Radojković, D., Ćalija, B., Strugarević, E., Radak, Đ.,& Kovač, M.. (2016). Uticaj CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 35(1), 26-33.
https://doi.org/10.1515/jomb-2015-0009

Bačković D, Ignjatović S, Rakićević L, Kušić-Tišma J, Radojković D, Ćalija B, Strugarević E, Radak Đ, Kovač M. Uticaj CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije. in Journal of Medical Biochemistry. 2016;35(1):26-33.
doi:10.1515/jomb-2015-0009 .

Bačković, Dragana, Ignjatović, Svetlana, Rakićević, Ljiljana, Kušić-Tišma, Jelena, Radojković, Dragica, Ćalija, Branko, Strugarević, Evgenija, Radak, Đorđe, Kovač, Mirjana, "Uticaj CYP2C19*2 varijante gena na terapijski odgovor u toku primene klopidogrela kod bolesnika sa stenozom karotidne arterije" in Journal of Medical Biochemistry, 35, no. 1 (2016):26-33,
https://doi.org/10.1515/jomb-2015-0009 . .

TY  - JOUR
AU  - Backović, Dragana
AU  - Ignjatović, Svetlana
AU  - Rakićević, Ljiljana
AU  - Novković, Mirjana
AU  - Kušić-Tišma, Jelena
AU  - Radojković, Dragica
AU  - Strugarević, Evgenija
AU  - Calija, Branko
AU  - Radak, Djordje
AU  - Kovač, Mirjana
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/920
AB  - Objectives: A considerable number of patients do not achieve an adequate response to clopidogrel. Our study aimed to evaluate genetic and non-genetic factors as possible risks for clopidogrel high on-treatment platelet reactivity (HTPR) in patients (n=112) with carotid artery stenosis undergoing endarterectomy (CEA). Methods: Using multiple-electrode impedance aggregometry (MEA) the antiplatelet effectiveness of clopidogrel was measured after 24 h, 7 and 30 days of clopidogrel treatment, which was introduced after elective CEA at a dose of 75 mg daily, for at least 30 days. Results: HTPR was observed among 25% patients after clopidogrel therapy for 30 days. Further analysis showed that 53.3% of patients carrying the CYP2C19*2 gene variant had clopidogrel-HTPR, while in the wild type group there were 14.6% (p lt 0.001). Multivariate logistic regression analysis identified the CYP2C19*2 variant allele (OR 4.384; 95% CI 1.296-14.833, p=0.017) and high total cholesterol level (OR 2.090; 95% CI 1.263-3.459, p=0.004) as the only independent risk factors for clopidogrel-HTPR. Conclusion: The CYP2C19*2 gene variant and high total cholesterol level were major factors for clopidogrel-HTPR in patients with carotid artery stenosis undergoing CEA.
PB  - Bentham Science Publ Ltd, Sharjah
T2  - Current Vascular Pharmacology
T1  - Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study
EP  - 569
IS  - 6
SP  - 563
VL  - 14
DO  - 10.2174/1570161114666160714103148
ER  - 

@article{
author = "Backović, Dragana and Ignjatović, Svetlana and Rakićević, Ljiljana and Novković, Mirjana and Kušić-Tišma, Jelena and Radojković, Dragica and Strugarević, Evgenija and Calija, Branko and Radak, Djordje and Kovač, Mirjana",
year = "2016",
abstract = "Objectives: A considerable number of patients do not achieve an adequate response to clopidogrel. Our study aimed to evaluate genetic and non-genetic factors as possible risks for clopidogrel high on-treatment platelet reactivity (HTPR) in patients (n=112) with carotid artery stenosis undergoing endarterectomy (CEA). Methods: Using multiple-electrode impedance aggregometry (MEA) the antiplatelet effectiveness of clopidogrel was measured after 24 h, 7 and 30 days of clopidogrel treatment, which was introduced after elective CEA at a dose of 75 mg daily, for at least 30 days. Results: HTPR was observed among 25% patients after clopidogrel therapy for 30 days. Further analysis showed that 53.3% of patients carrying the CYP2C19*2 gene variant had clopidogrel-HTPR, while in the wild type group there were 14.6% (p lt 0.001). Multivariate logistic regression analysis identified the CYP2C19*2 variant allele (OR 4.384; 95% CI 1.296-14.833, p=0.017) and high total cholesterol level (OR 2.090; 95% CI 1.263-3.459, p=0.004) as the only independent risk factors for clopidogrel-HTPR. Conclusion: The CYP2C19*2 gene variant and high total cholesterol level were major factors for clopidogrel-HTPR in patients with carotid artery stenosis undergoing CEA.",
publisher = "Bentham Science Publ Ltd, Sharjah",
journal = "Current Vascular Pharmacology",
title = "Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study",
pages = "569-563",
number = "6",
volume = "14",
doi = "10.2174/1570161114666160714103148"
}

Backović, D., Ignjatović, S., Rakićević, L., Novković, M., Kušić-Tišma, J., Radojković, D., Strugarević, E., Calija, B., Radak, D.,& Kovač, M.. (2016). Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study. in Current Vascular Pharmacology
Bentham Science Publ Ltd, Sharjah., 14(6), 563-569.
https://doi.org/10.2174/1570161114666160714103148

Backović D, Ignjatović S, Rakićević L, Novković M, Kušić-Tišma J, Radojković D, Strugarević E, Calija B, Radak D, Kovač M. Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study. in Current Vascular Pharmacology. 2016;14(6):563-569.
doi:10.2174/1570161114666160714103148 .

Backović, Dragana, Ignjatović, Svetlana, Rakićević, Ljiljana, Novković, Mirjana, Kušić-Tišma, Jelena, Radojković, Dragica, Strugarević, Evgenija, Calija, Branko, Radak, Djordje, Kovač, Mirjana, "Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study" in Current Vascular Pharmacology, 14, no. 6 (2016):563-569,
https://doi.org/10.2174/1570161114666160714103148 . .

TY  - CONF
AU  - Backović, D.
AU  - Ignjatović, S.
AU  - Rakićević, Ljiljana
AU  - Novković, Mirjana
AU  - Kušić-Tišma, Jelena
AU  - Radojković, Dragica
AU  - Strugarević, E.
AU  - Calija, B.
AU  - Radak, D.
AU  - Kovač, Mirjana
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/940
PB  - Wiley-Blackwell, Hoboken
C3  - Journal of Thrombosis and Haemostasis
T1  - Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy
EP  - 110
SP  - 110
VL  - 14
UR  - https://hdl.handle.net/21.15107/rcub_imagine_940
ER  - 

@conference{
author = "Backović, D. and Ignjatović, S. and Rakićević, Ljiljana and Novković, Mirjana and Kušić-Tišma, Jelena and Radojković, Dragica and Strugarević, E. and Calija, B. and Radak, D. and Kovač, Mirjana",
year = "2016",
publisher = "Wiley-Blackwell, Hoboken",
journal = "Journal of Thrombosis and Haemostasis",
title = "Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy",
pages = "110-110",
volume = "14",
url = "https://hdl.handle.net/21.15107/rcub_imagine_940"
}

Backović, D., Ignjatović, S., Rakićević, L., Novković, M., Kušić-Tišma, J., Radojković, D., Strugarević, E., Calija, B., Radak, D.,& Kovač, M.. (2016). Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy. in Journal of Thrombosis and Haemostasis
Wiley-Blackwell, Hoboken., 14, 110-110.
https://hdl.handle.net/21.15107/rcub_imagine_940

Backović D, Ignjatović S, Rakićević L, Novković M, Kušić-Tišma J, Radojković D, Strugarević E, Calija B, Radak D, Kovač M. Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy. in Journal of Thrombosis and Haemostasis. 2016;14:110-110.
https://hdl.handle.net/21.15107/rcub_imagine_940 .

Backović, D., Ignjatović, S., Rakićević, Ljiljana, Novković, Mirjana, Kušić-Tišma, Jelena, Radojković, Dragica, Strugarević, E., Calija, B., Radak, D., Kovač, Mirjana, "Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy" in Journal of Thrombosis and Haemostasis, 14 (2016):110-110,
https://hdl.handle.net/21.15107/rcub_imagine_940 .

TY  - JOUR
AU  - Tomić, Branko
AU  - Kušić-Tišma, Jelena
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/816
AB  - Replication of DNA in multicellular organisms initiates from origin of replication (ori) sequences, which significantly differ in length and complexity. One of the best characterized is hamster dihydrofolate reductase (DHFR), which contains the ori-beta sequence with several functionally relevant domains, such as an AT-rich region, dinucleotide repeat element (DNR), sequence-induced bend DNA (BEND) and a RIP60 protein-binding site (RIP60). Prior to initiation, ori sequences are recognized by origin recognition complex (ORC), which is a hetero hexamer complex that serves as the landing pad for proteins of the pre-replication complex. The function of each ORC subunit is still unclear. In this study, we analyze the function of subunit 4 of the human ORC complex (HsOrc4) in interaction with a plasmid bearing the ori-beta DHFR sequence. We show that the topologically closed DHFR ori-beta replicator contains a bubble-like structure within its AT-rich region and that it is reversibly modified in the interaction with HsOrc4. The non-canonical structure of the AT-rich region in the topologically closed ori sequence is recognized and changed by HsOrc4 using the energy of supercoiled DNA. These findings could help to further elucidate DNA replication and its possible association with human genetic diseases.
PB  - Walter De Gruyter Gmbh, Berlin
T2  - Cellular & Molecular Biology Letters
T1  - Hsorc4-dependent DNA remodeling of the ori-beta dhfr replicator
EP  - 561
IS  - 4
SP  - 549
VL  - 20
DO  - 10.1515/cmble-2015-0032
ER  - 

@article{
author = "Tomić, Branko and Kušić-Tišma, Jelena",
year = "2015",
abstract = "Replication of DNA in multicellular organisms initiates from origin of replication (ori) sequences, which significantly differ in length and complexity. One of the best characterized is hamster dihydrofolate reductase (DHFR), which contains the ori-beta sequence with several functionally relevant domains, such as an AT-rich region, dinucleotide repeat element (DNR), sequence-induced bend DNA (BEND) and a RIP60 protein-binding site (RIP60). Prior to initiation, ori sequences are recognized by origin recognition complex (ORC), which is a hetero hexamer complex that serves as the landing pad for proteins of the pre-replication complex. The function of each ORC subunit is still unclear. In this study, we analyze the function of subunit 4 of the human ORC complex (HsOrc4) in interaction with a plasmid bearing the ori-beta DHFR sequence. We show that the topologically closed DHFR ori-beta replicator contains a bubble-like structure within its AT-rich region and that it is reversibly modified in the interaction with HsOrc4. The non-canonical structure of the AT-rich region in the topologically closed ori sequence is recognized and changed by HsOrc4 using the energy of supercoiled DNA. These findings could help to further elucidate DNA replication and its possible association with human genetic diseases.",
publisher = "Walter De Gruyter Gmbh, Berlin",
journal = "Cellular & Molecular Biology Letters",
title = "Hsorc4-dependent DNA remodeling of the ori-beta dhfr replicator",
pages = "561-549",
number = "4",
volume = "20",
doi = "10.1515/cmble-2015-0032"
}

Tomić, B.,& Kušić-Tišma, J.. (2015). Hsorc4-dependent DNA remodeling of the ori-beta dhfr replicator. in Cellular & Molecular Biology Letters
Walter De Gruyter Gmbh, Berlin., 20(4), 549-561.
https://doi.org/10.1515/cmble-2015-0032

Tomić B, Kušić-Tišma J. Hsorc4-dependent DNA remodeling of the ori-beta dhfr replicator. in Cellular & Molecular Biology Letters. 2015;20(4):549-561.
doi:10.1515/cmble-2015-0032 .

Tomić, Branko, Kušić-Tišma, Jelena, "Hsorc4-dependent DNA remodeling of the ori-beta dhfr replicator" in Cellular & Molecular Biology Letters, 20, no. 4 (2015):549-561,
https://doi.org/10.1515/cmble-2015-0032 . .

TY  - JOUR
AU  - Kovač, Mirjana
AU  - Rakićević, Ljiljana
AU  - Kušić-Tišma, Jelena
AU  - Radojković, Dragica
PY  - 2013
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/679
AB  - Several studies have linked mutations in the genes encoding cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex 1 (VKORC1) to a reduced VKA dose requirement and an increased risk of bleeding. Nevertheless, implementation of genotyping as a routine practice is still controversial. Our study was conducted in order to investigate the impact of genetic factors, presence of VKORC1-c.1639A, CYP2C*2 and CYP2C*3 among outpatients referred to Anticoagulation Service due to extremely unstable anticoagulant therapy. From 2008 to 2011, 68 patients, mean age 65.9, were included in the study. They were referred from primary care physicians due to inability to sustain the therapeutic range in the period of initiation of anticoagulant therapy. Genotyping results showed that 17 (25 %) of them were carriers of both CYP2C9 and VKORC1 variant alleles, 38 (55.9 %) were carriers of VKORC1 c.1639AA, 6 (8.8 %) were carriers of CYP2C9 variant alleles, while 7 (10.3 %) of them were carriers of wild type alleles. INR control upon admission showed that 34 (50 %) of them were over-anticoagulated, while 12 (17.6 %) of them had subsequent bleeding complications. Among over-anticoagulated patients, 32 were carriers of mutated alleles in both CYP2C9 and VKORC1 gene or VKORC1 alone, while 2 of patients carried wild type alleles. In addition to presence of CYP2C9 or VKORC 1 alleles, older age was an important factor related to a lower dose and risk for over-anticoagulation. Genotype (CYP2C9/VKORC1) and age are the most important factors that could predispose an extreme response and subsequent bleeding complications during the initiation of VKA.
PB  - Springer, Dordrecht
T2  - Journal of Thrombosis and Thrombolysis
T1  - Pharmacogenetic tests could be helpful in predicting of VKA maintenance dose in elderly patients at treatment initiation
EP  - 94
IS  - 1
SP  - 90
VL  - 35
DO  - 10.1007/s11239-012-0769-8
ER  - 

@article{
author = "Kovač, Mirjana and Rakićević, Ljiljana and Kušić-Tišma, Jelena and Radojković, Dragica",
year = "2013",
abstract = "Several studies have linked mutations in the genes encoding cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex 1 (VKORC1) to a reduced VKA dose requirement and an increased risk of bleeding. Nevertheless, implementation of genotyping as a routine practice is still controversial. Our study was conducted in order to investigate the impact of genetic factors, presence of VKORC1-c.1639A, CYP2C*2 and CYP2C*3 among outpatients referred to Anticoagulation Service due to extremely unstable anticoagulant therapy. From 2008 to 2011, 68 patients, mean age 65.9, were included in the study. They were referred from primary care physicians due to inability to sustain the therapeutic range in the period of initiation of anticoagulant therapy. Genotyping results showed that 17 (25 %) of them were carriers of both CYP2C9 and VKORC1 variant alleles, 38 (55.9 %) were carriers of VKORC1 c.1639AA, 6 (8.8 %) were carriers of CYP2C9 variant alleles, while 7 (10.3 %) of them were carriers of wild type alleles. INR control upon admission showed that 34 (50 %) of them were over-anticoagulated, while 12 (17.6 %) of them had subsequent bleeding complications. Among over-anticoagulated patients, 32 were carriers of mutated alleles in both CYP2C9 and VKORC1 gene or VKORC1 alone, while 2 of patients carried wild type alleles. In addition to presence of CYP2C9 or VKORC 1 alleles, older age was an important factor related to a lower dose and risk for over-anticoagulation. Genotype (CYP2C9/VKORC1) and age are the most important factors that could predispose an extreme response and subsequent bleeding complications during the initiation of VKA.",
publisher = "Springer, Dordrecht",
journal = "Journal of Thrombosis and Thrombolysis",
title = "Pharmacogenetic tests could be helpful in predicting of VKA maintenance dose in elderly patients at treatment initiation",
pages = "94-90",
number = "1",
volume = "35",
doi = "10.1007/s11239-012-0769-8"
}

Kovač, M., Rakićević, L., Kušić-Tišma, J.,& Radojković, D.. (2013). Pharmacogenetic tests could be helpful in predicting of VKA maintenance dose in elderly patients at treatment initiation. in Journal of Thrombosis and Thrombolysis
Springer, Dordrecht., 35(1), 90-94.
https://doi.org/10.1007/s11239-012-0769-8

Kovač M, Rakićević L, Kušić-Tišma J, Radojković D. Pharmacogenetic tests could be helpful in predicting of VKA maintenance dose in elderly patients at treatment initiation. in Journal of Thrombosis and Thrombolysis. 2013;35(1):90-94.
doi:10.1007/s11239-012-0769-8 .

Kovač, Mirjana, Rakićević, Ljiljana, Kušić-Tišma, Jelena, Radojković, Dragica, "Pharmacogenetic tests could be helpful in predicting of VKA maintenance dose in elderly patients at treatment initiation" in Journal of Thrombosis and Thrombolysis, 35, no. 1 (2013):90-94,
https://doi.org/10.1007/s11239-012-0769-8 . .

TY  - JOUR
AU  - Rakićević, Ljiljana
AU  - Kušić-Tišma, Jelena
AU  - Kovač, Mirjana
AU  - Backović, Dragana
AU  - Radojković, Dragica 
PY  - 2013
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/651
AB  - During the last decade genetic factors affecting coumarin therapy have been extensively investigated. The most important genes appear to be CYP2C9 and VKORC1, and different studies have shown that DNA testing can dramatically improve the safety and effectiveness of the therapy. However, the implementation of pharmacogenetic testing in everyday practice is still not a reality. Facilities and ability to get results before the start of therapy are very important. The implementation of specific methodology and equipment for particular type of diagnostics can represent a serious, even impossible, financial hurdle to overcome (especially in developing countries). For this reason, the use of every tool that contributes to rationalization of the existing methods can be a considerable asset. Therefore, we set the goal to rationalize our current DNA sequencing based protocol for analysis of the VKORC1 c.-1639G gt A, CYP2C9*2 and CYP2C9*3 variant alleles, in order to obtain shorter and easier procedure. Simplification of the protocol was achieved by setting up multiplex PCR and omitting DNA extraction. This rationalization of the existing DNA sequencing based procedure allows getting results in 12 hours. The new protocol was tested on 118 samples. Obtained results have shown full accordance to those obtained with previous, non-modified protocol. Therefore, given the circumstances, we consider that protocol for pharmocogenetic testing should be made more accessible - both to doctors and patients. It is one of the prerequisites in order to make genotyping prior to the therapy common practice.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Scandinavian Journal of Clinical & Laboratory Investigation
T1  - Rationalized DNA sequencing-based protocol for genotyping patients receiving coumarin therapy
EP  - 527
IS  - 6
SP  - 523
VL  - 73
DO  - 10.3109/00365513.2013.809142
ER  - 

@article{
author = "Rakićević, Ljiljana and Kušić-Tišma, Jelena and Kovač, Mirjana and Backović, Dragana and Radojković, Dragica ",
year = "2013",
abstract = "During the last decade genetic factors affecting coumarin therapy have been extensively investigated. The most important genes appear to be CYP2C9 and VKORC1, and different studies have shown that DNA testing can dramatically improve the safety and effectiveness of the therapy. However, the implementation of pharmacogenetic testing in everyday practice is still not a reality. Facilities and ability to get results before the start of therapy are very important. The implementation of specific methodology and equipment for particular type of diagnostics can represent a serious, even impossible, financial hurdle to overcome (especially in developing countries). For this reason, the use of every tool that contributes to rationalization of the existing methods can be a considerable asset. Therefore, we set the goal to rationalize our current DNA sequencing based protocol for analysis of the VKORC1 c.-1639G gt A, CYP2C9*2 and CYP2C9*3 variant alleles, in order to obtain shorter and easier procedure. Simplification of the protocol was achieved by setting up multiplex PCR and omitting DNA extraction. This rationalization of the existing DNA sequencing based procedure allows getting results in 12 hours. The new protocol was tested on 118 samples. Obtained results have shown full accordance to those obtained with previous, non-modified protocol. Therefore, given the circumstances, we consider that protocol for pharmocogenetic testing should be made more accessible - both to doctors and patients. It is one of the prerequisites in order to make genotyping prior to the therapy common practice.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Scandinavian Journal of Clinical & Laboratory Investigation",
title = "Rationalized DNA sequencing-based protocol for genotyping patients receiving coumarin therapy",
pages = "527-523",
number = "6",
volume = "73",
doi = "10.3109/00365513.2013.809142"
}

Rakićević, L., Kušić-Tišma, J., Kovač, M., Backović, D.,& Radojković, D.. (2013). Rationalized DNA sequencing-based protocol for genotyping patients receiving coumarin therapy. in Scandinavian Journal of Clinical & Laboratory Investigation
Taylor & Francis Ltd, Abingdon., 73(6), 523-527.
https://doi.org/10.3109/00365513.2013.809142

Rakićević L, Kušić-Tišma J, Kovač M, Backović D, Radojković D. Rationalized DNA sequencing-based protocol for genotyping patients receiving coumarin therapy. in Scandinavian Journal of Clinical & Laboratory Investigation. 2013;73(6):523-527.
doi:10.3109/00365513.2013.809142 .

Rakićević, Ljiljana, Kušić-Tišma, Jelena, Kovač, Mirjana, Backović, Dragana, Radojković, Dragica , "Rationalized DNA sequencing-based protocol for genotyping patients receiving coumarin therapy" in Scandinavian Journal of Clinical & Laboratory Investigation, 73, no. 6 (2013):523-527,
https://doi.org/10.3109/00365513.2013.809142 . .

TY  - CONF
AU  - Kovač, Mirjana
AU  - Rakićević, Ljiljana
AU  - Kušić-Tišma, Jelena
AU  - Radojković, Dragica
PY  - 2012
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/591
PB  - Pergamon-Elsevier Science Ltd, Oxford
C3  - Thrombosis Research
T1  - Pharmacogenetic tests could be helpful in predicting of VKA maintenance dose in elderly patients at treatment initiation
EP  - S119
SP  - S119
VL  - 130
DO  - 10.1016/j.thromres.2012.08.051
ER  - 

@conference{
author = "Kovač, Mirjana and Rakićević, Ljiljana and Kušić-Tišma, Jelena and Radojković, Dragica",
year = "2012",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Thrombosis Research",
title = "Pharmacogenetic tests could be helpful in predicting of VKA maintenance dose in elderly patients at treatment initiation",
pages = "S119-S119",
volume = "130",
doi = "10.1016/j.thromres.2012.08.051"
}

Kovač, M., Rakićević, L., Kušić-Tišma, J.,& Radojković, D.. (2012). Pharmacogenetic tests could be helpful in predicting of VKA maintenance dose in elderly patients at treatment initiation. in Thrombosis Research
Pergamon-Elsevier Science Ltd, Oxford., 130, S119-S119.
https://doi.org/10.1016/j.thromres.2012.08.051

Kovač M, Rakićević L, Kušić-Tišma J, Radojković D. Pharmacogenetic tests could be helpful in predicting of VKA maintenance dose in elderly patients at treatment initiation. in Thrombosis Research. 2012;130:S119-S119.
doi:10.1016/j.thromres.2012.08.051 .

Kovač, Mirjana, Rakićević, Ljiljana, Kušić-Tišma, Jelena, Radojković, Dragica, "Pharmacogenetic tests could be helpful in predicting of VKA maintenance dose in elderly patients at treatment initiation" in Thrombosis Research, 130 (2012):S119-S119,
https://doi.org/10.1016/j.thromres.2012.08.051 . .

TY  - JOUR
AU  - Kušić-Tišma, Jelena
AU  - Tomić, Branko
AU  - Divac Rankov, Aleksandra
AU  - Kojić, Snežana
PY  - 2010
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/408
AB  - In higher eukaryotes mechanism of DNA replication origin recognition and binding by origin recognition complex (ORC) is still unknown. Origin transfer studies have shown that origin sites are genetically determined, containing functionally interchangeable modules. One of such modules from the human lamin B2 origin of replication has the ability to adopt unorthodox structure partly composed of intramolecular triplex. Sequences involved in triplex formation coincide with ORC binding sites both in vitro and in vivo. To explore potential significance of unorthodox DNA structures in origin recognition by ORC, we tested DNA binding properties of human ORC subunit 4 (HsOrc4) which has independent DNA binding activity in vitro and similar binding characteristics as ORC holocomplex. Our results demonstrated that DNA binding activity of HsOrc4 depends on length and structure of DNA with triplex being the protein's preferred binding target. Such feature could play part in origin selection through directing ORC to DNA sequence prone to adopt unorthodox structure.
PB  - Springer, Dordrecht
T2  - Molecular Biology Reports
T1  - Human initiation protein Orc4 prefers triple stranded DNA
EP  - 2322
IS  - 5
SP  - 2317
VL  - 37
DO  - 10.1007/s11033-009-9735-8
ER  - 

@article{
author = "Kušić-Tišma, Jelena and Tomić, Branko and Divac Rankov, Aleksandra and Kojić, Snežana",
year = "2010",
abstract = "In higher eukaryotes mechanism of DNA replication origin recognition and binding by origin recognition complex (ORC) is still unknown. Origin transfer studies have shown that origin sites are genetically determined, containing functionally interchangeable modules. One of such modules from the human lamin B2 origin of replication has the ability to adopt unorthodox structure partly composed of intramolecular triplex. Sequences involved in triplex formation coincide with ORC binding sites both in vitro and in vivo. To explore potential significance of unorthodox DNA structures in origin recognition by ORC, we tested DNA binding properties of human ORC subunit 4 (HsOrc4) which has independent DNA binding activity in vitro and similar binding characteristics as ORC holocomplex. Our results demonstrated that DNA binding activity of HsOrc4 depends on length and structure of DNA with triplex being the protein's preferred binding target. Such feature could play part in origin selection through directing ORC to DNA sequence prone to adopt unorthodox structure.",
publisher = "Springer, Dordrecht",
journal = "Molecular Biology Reports",
title = "Human initiation protein Orc4 prefers triple stranded DNA",
pages = "2322-2317",
number = "5",
volume = "37",
doi = "10.1007/s11033-009-9735-8"
}

Kušić-Tišma, J., Tomić, B., Divac Rankov, A.,& Kojić, S.. (2010). Human initiation protein Orc4 prefers triple stranded DNA. in Molecular Biology Reports
Springer, Dordrecht., 37(5), 2317-2322.
https://doi.org/10.1007/s11033-009-9735-8

Kušić-Tišma J, Tomić B, Divac Rankov A, Kojić S. Human initiation protein Orc4 prefers triple stranded DNA. in Molecular Biology Reports. 2010;37(5):2317-2322.
doi:10.1007/s11033-009-9735-8 .

Kušić-Tišma, Jelena, Tomić, Branko, Divac Rankov, Aleksandra, Kojić, Snežana, "Human initiation protein Orc4 prefers triple stranded DNA" in Molecular Biology Reports, 37, no. 5 (2010):2317-2322,
https://doi.org/10.1007/s11033-009-9735-8 . .

TY  - JOUR
AU  - Divac Rankov, Aleksandra
AU  - Tomić, Branko
AU  - Kušić-Tišma, Jelena
PY  - 2010
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/467
AB  - Humani protein ORC4, podjedinica ORC kompleksa (eng. Origin Recognition Complex), pripada familiji AAA+ adenozin-trifosfat (ATP)-aza povezanih sa različitim funkcijama u ćeliji. Za pripadnike ove familije proteina je karakteristično da je ATP neophodan za njihovu funkciju i da po vezivanju ATP-a prolaze kroz konformacionu promenu ili je indukuju u svojim partnerima. Humani protein ORC4 indukuje strukturne promene u supstratnim DNK, tako što promoviše renaturaciju i formiranje nekanonskih struktura, kao i konverziju jednolančanih oligonukleotida u višelančane strukture. ATP je neophodan za ove funkcije ORC4 proteina, što je pokazano analizom aktivnosti mutanta koji ne može da veže ATP, i koji nije aktivan u ovim reakcijama. Da bismo bliže ispitali ulogu ATP-a u aktivnosti ORC4 napravljen je protein sa mutacijom u domenu za hidrolizu ATP-a (Voker B motiv), koji ima očuvanu ATP-vezivnu aktivnost. Ovaj mutant je bio aktivan u reakcijama restrukturiranja DNK, tako da se može zaključiti da je uloga ATP-a strukturna, kao kofaktora, i da njegova hidroliza nije neophodna za funkciju humanog proteina ORC4.
AB  - Human origin recognition complex 4 (ORC4) protein, a subunit of the origin recognition complex, belongs to the AAA+ superfamily of adenosine triphosphate (ATP) ases. Proteins belonging to this family require ATP for their function and interactions with ATP lead to conformational changes in them or in their partners. Human ORC4 protein induces structural changes in DNA substrates, promoting renaturation and formation of non-canonical structures, as well as conversion of single-stranded into multi-stranded oligonucleotide structures. The aim of this study was to further investigate the role of ATP in the function of human ORC4 protein. For this purpose, a mutant in the conserved Walker B motif of ORC4, which is able to bind but not to hydrolyze ATP, was constructed and its activity in DNA restructuring reactions was investigated. The obtained results showed that ATP hydrolysis is not necessary for the function of human ORC4. It is proposed that ATP has a structural role as a cofactor in the function of human ORC4 as a DNA restructuring agent.
PB  - Srpsko hemijsko društvo, Beograd
T2  - Journal of the Serbian Chemical Society
T1  - Uloga ATP-a u funkciji humanog proteina ORC4
T1  - The role of adenosine triphosphate in the function of human origin recognition complex 4 protein
EP  - 322
IS  - 3
SP  - 317
VL  - 75
DO  - 10.2998/JSC090724019D
ER  - 

@article{
author = "Divac Rankov, Aleksandra and Tomić, Branko and Kušić-Tišma, Jelena",
year = "2010",
abstract = "Humani protein ORC4, podjedinica ORC kompleksa (eng. Origin Recognition Complex), pripada familiji AAA+ adenozin-trifosfat (ATP)-aza povezanih sa različitim funkcijama u ćeliji. Za pripadnike ove familije proteina je karakteristično da je ATP neophodan za njihovu funkciju i da po vezivanju ATP-a prolaze kroz konformacionu promenu ili je indukuju u svojim partnerima. Humani protein ORC4 indukuje strukturne promene u supstratnim DNK, tako što promoviše renaturaciju i formiranje nekanonskih struktura, kao i konverziju jednolančanih oligonukleotida u višelančane strukture. ATP je neophodan za ove funkcije ORC4 proteina, što je pokazano analizom aktivnosti mutanta koji ne može da veže ATP, i koji nije aktivan u ovim reakcijama. Da bismo bliže ispitali ulogu ATP-a u aktivnosti ORC4 napravljen je protein sa mutacijom u domenu za hidrolizu ATP-a (Voker B motiv), koji ima očuvanu ATP-vezivnu aktivnost. Ovaj mutant je bio aktivan u reakcijama restrukturiranja DNK, tako da se može zaključiti da je uloga ATP-a strukturna, kao kofaktora, i da njegova hidroliza nije neophodna za funkciju humanog proteina ORC4., Human origin recognition complex 4 (ORC4) protein, a subunit of the origin recognition complex, belongs to the AAA+ superfamily of adenosine triphosphate (ATP) ases. Proteins belonging to this family require ATP for their function and interactions with ATP lead to conformational changes in them or in their partners. Human ORC4 protein induces structural changes in DNA substrates, promoting renaturation and formation of non-canonical structures, as well as conversion of single-stranded into multi-stranded oligonucleotide structures. The aim of this study was to further investigate the role of ATP in the function of human ORC4 protein. For this purpose, a mutant in the conserved Walker B motif of ORC4, which is able to bind but not to hydrolyze ATP, was constructed and its activity in DNA restructuring reactions was investigated. The obtained results showed that ATP hydrolysis is not necessary for the function of human ORC4. It is proposed that ATP has a structural role as a cofactor in the function of human ORC4 as a DNA restructuring agent.",
publisher = "Srpsko hemijsko društvo, Beograd",
journal = "Journal of the Serbian Chemical Society",
title = "Uloga ATP-a u funkciji humanog proteina ORC4, The role of adenosine triphosphate in the function of human origin recognition complex 4 protein",
pages = "322-317",
number = "3",
volume = "75",
doi = "10.2998/JSC090724019D"
}

Divac Rankov, A., Tomić, B.,& Kušić-Tišma, J.. (2010). Uloga ATP-a u funkciji humanog proteina ORC4. in Journal of the Serbian Chemical Society
Srpsko hemijsko društvo, Beograd., 75(3), 317-322.
https://doi.org/10.2998/JSC090724019D

Divac Rankov A, Tomić B, Kušić-Tišma J. Uloga ATP-a u funkciji humanog proteina ORC4. in Journal of the Serbian Chemical Society. 2010;75(3):317-322.
doi:10.2998/JSC090724019D .

Divac Rankov, Aleksandra, Tomić, Branko, Kušić-Tišma, Jelena, "Uloga ATP-a u funkciji humanog proteina ORC4" in Journal of the Serbian Chemical Society, 75, no. 3 (2010):317-322,
https://doi.org/10.2998/JSC090724019D . .

TY  - JOUR
AU  - Stanković, Marija
AU  - Nikolić, Aleksandra
AU  - Divac Rankov, Aleksandra
AU  - Tomović, Andrija
AU  - Petrović-Stanojević, Nataša
AU  - Anđelić, Marina
AU  - Dopudja-Pantić, Vesna
AU  - Surlan, Mirjana
AU  - Vujicić, Ivan
AU  - Ponomarev, Dimitrije
AU  - Mitić-Milikić, Marija
AU  - Kušić-Tišma, Jelena
AU  - Radojković, Dragica
PY  - 2008
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/316
AB  - Chronic obstructive pulmonary disease (COPD) is a complex disease influenced by genetic and environmental factors. Cystic fibrosis transmembrane conductance regulator (CFTR) protein is an important component of the lung tissue homeostasis, involved in the regulation of the rate of mucociliary clearance. As it is known that certain CFTR variants have consequences on the function of CFTR protein, the aim of this study was to examine the possible role of F508del, M470V, Tn locus, and R75Q variants in COPD development and modulation. Total number of 86 COPD patients and 102 control subjects were included in the study. Possible association between COPD susceptibility, severity, and onset of the disease and allele or genotype of four analyzed CFTR variants was examined. No associations were detected between COPD development, onset of the disease and tested CFTR alleles and genotypes. However, VV470 genotype was associated with mild/moderate COPD stages in comparison to severe/very severe ones (OR = 0.29, 95% CI = 0.11-0.80, p = 0.016). Our study showed that patients with VV470 genotype had a 3.4-fold decreased risk for the appearance of severe/very severe COPD symptoms, and the obtained results indicate that this genotype may have a protective role. These results also suggest the importance of studying CFTR gene as a modifier of this disease.
PB  - Mary Ann Liebert, Inc, New Rochelle
T2  - Genetic Testing
T1  - The CFTR M470V gene variant as a potential modifier of COPD severity: Study of Serbian population
EP  - 362
IS  - 3
SP  - 357
VL  - 12
DO  - 10.1089/gte.2007.0069
ER  - 

@article{
author = "Stanković, Marija and Nikolić, Aleksandra and Divac Rankov, Aleksandra and Tomović, Andrija and Petrović-Stanojević, Nataša and Anđelić, Marina and Dopudja-Pantić, Vesna and Surlan, Mirjana and Vujicić, Ivan and Ponomarev, Dimitrije and Mitić-Milikić, Marija and Kušić-Tišma, Jelena and Radojković, Dragica",
year = "2008",
abstract = "Chronic obstructive pulmonary disease (COPD) is a complex disease influenced by genetic and environmental factors. Cystic fibrosis transmembrane conductance regulator (CFTR) protein is an important component of the lung tissue homeostasis, involved in the regulation of the rate of mucociliary clearance. As it is known that certain CFTR variants have consequences on the function of CFTR protein, the aim of this study was to examine the possible role of F508del, M470V, Tn locus, and R75Q variants in COPD development and modulation. Total number of 86 COPD patients and 102 control subjects were included in the study. Possible association between COPD susceptibility, severity, and onset of the disease and allele or genotype of four analyzed CFTR variants was examined. No associations were detected between COPD development, onset of the disease and tested CFTR alleles and genotypes. However, VV470 genotype was associated with mild/moderate COPD stages in comparison to severe/very severe ones (OR = 0.29, 95% CI = 0.11-0.80, p = 0.016). Our study showed that patients with VV470 genotype had a 3.4-fold decreased risk for the appearance of severe/very severe COPD symptoms, and the obtained results indicate that this genotype may have a protective role. These results also suggest the importance of studying CFTR gene as a modifier of this disease.",
publisher = "Mary Ann Liebert, Inc, New Rochelle",
journal = "Genetic Testing",
title = "The CFTR M470V gene variant as a potential modifier of COPD severity: Study of Serbian population",
pages = "362-357",
number = "3",
volume = "12",
doi = "10.1089/gte.2007.0069"
}

Stanković, M., Nikolić, A., Divac Rankov, A., Tomović, A., Petrović-Stanojević, N., Anđelić, M., Dopudja-Pantić, V., Surlan, M., Vujicić, I., Ponomarev, D., Mitić-Milikić, M., Kušić-Tišma, J.,& Radojković, D.. (2008). The CFTR M470V gene variant as a potential modifier of COPD severity: Study of Serbian population. in Genetic Testing
Mary Ann Liebert, Inc, New Rochelle., 12(3), 357-362.
https://doi.org/10.1089/gte.2007.0069

Stanković M, Nikolić A, Divac Rankov A, Tomović A, Petrović-Stanojević N, Anđelić M, Dopudja-Pantić V, Surlan M, Vujicić I, Ponomarev D, Mitić-Milikić M, Kušić-Tišma J, Radojković D. The CFTR M470V gene variant as a potential modifier of COPD severity: Study of Serbian population. in Genetic Testing. 2008;12(3):357-362.
doi:10.1089/gte.2007.0069 .

Stanković, Marija, Nikolić, Aleksandra, Divac Rankov, Aleksandra, Tomović, Andrija, Petrović-Stanojević, Nataša, Anđelić, Marina, Dopudja-Pantić, Vesna, Surlan, Mirjana, Vujicić, Ivan, Ponomarev, Dimitrije, Mitić-Milikić, Marija, Kušić-Tišma, Jelena, Radojković, Dragica, "The CFTR M470V gene variant as a potential modifier of COPD severity: Study of Serbian population" in Genetic Testing, 12, no. 3 (2008):357-362,
https://doi.org/10.1089/gte.2007.0069 . .

TY  - JOUR
AU  - Stefanović, Dragana
AU  - Kušić-Tišma, Jelena
AU  - Divac Rankov, Aleksandra
AU  - Tomić, Branko
PY  - 2008
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/306
AB  - Many genomic sequences, DNA replication origins included, contain specific structural motifs prone to alternative base pairing. Structural rearrangements of DNA require specific environmental conditions and could be favored by chemical agents or proteins. To improve our understanding of alternative conformations of origins and the manner in which they form, we have investigated the effect of DNA-binding, AAA+ protein human ORC4 on single-stranded origin DNA or various oligonucleotides. Here we demonstrate that human ORC4 stimulated formation of inter- and intramolecular T center dot A center dot T triplexes and created novel structures, such as homoadenine duplexes. Adenine-based structures were held together by Hoogsteen hydrogen bonds, as demonstrated on 7-deaza-dAMP- or dAMP-containing substrates, and characterized by increased thermal stability. Adenine pairing occurred only in the presence of human ORC4, in a neutral buffer supplemented with ATP and Mg2+ ions. The protein mutant that could not bind ATP was inactive in this reaction. Since the action of human ORC4 could be biologically important, its potential impact on DNA replication is discussed.
PB  - Amer Chemical Soc, Washington
T2  - Biochemistry
T1  - Formation of noncanonical DNA structures mediated by human ORC4, a protein component of the origin recognition complex
EP  - 8767
IS  - 33
SP  - 8760
VL  - 47
DO  - 10.1021/bi800684f
ER  - 

@article{
author = "Stefanović, Dragana and Kušić-Tišma, Jelena and Divac Rankov, Aleksandra and Tomić, Branko",
year = "2008",
abstract = "Many genomic sequences, DNA replication origins included, contain specific structural motifs prone to alternative base pairing. Structural rearrangements of DNA require specific environmental conditions and could be favored by chemical agents or proteins. To improve our understanding of alternative conformations of origins and the manner in which they form, we have investigated the effect of DNA-binding, AAA+ protein human ORC4 on single-stranded origin DNA or various oligonucleotides. Here we demonstrate that human ORC4 stimulated formation of inter- and intramolecular T center dot A center dot T triplexes and created novel structures, such as homoadenine duplexes. Adenine-based structures were held together by Hoogsteen hydrogen bonds, as demonstrated on 7-deaza-dAMP- or dAMP-containing substrates, and characterized by increased thermal stability. Adenine pairing occurred only in the presence of human ORC4, in a neutral buffer supplemented with ATP and Mg2+ ions. The protein mutant that could not bind ATP was inactive in this reaction. Since the action of human ORC4 could be biologically important, its potential impact on DNA replication is discussed.",
publisher = "Amer Chemical Soc, Washington",
journal = "Biochemistry",
title = "Formation of noncanonical DNA structures mediated by human ORC4, a protein component of the origin recognition complex",
pages = "8767-8760",
number = "33",
volume = "47",
doi = "10.1021/bi800684f"
}

Stefanović, D., Kušić-Tišma, J., Divac Rankov, A.,& Tomić, B.. (2008). Formation of noncanonical DNA structures mediated by human ORC4, a protein component of the origin recognition complex. in Biochemistry
Amer Chemical Soc, Washington., 47(33), 8760-8767.
https://doi.org/10.1021/bi800684f

Stefanović D, Kušić-Tišma J, Divac Rankov A, Tomić B. Formation of noncanonical DNA structures mediated by human ORC4, a protein component of the origin recognition complex. in Biochemistry. 2008;47(33):8760-8767.
doi:10.1021/bi800684f .

Stefanović, Dragana, Kušić-Tišma, Jelena, Divac Rankov, Aleksandra, Tomić, Branko, "Formation of noncanonical DNA structures mediated by human ORC4, a protein component of the origin recognition complex" in Biochemistry, 47, no. 33 (2008):8760-8767,
https://doi.org/10.1021/bi800684f . .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Kušić-Tišma, Jelena
AU  - Nikolić, Aleksandra
AU  - Divac Rankov, Aleksandra
AU  - Ristanović, Momčilo
AU  - Radojković, Dragica
PY  - 2007
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/291
AB  - Uvod/Cilj. Poremećena plodnost muškog partnera je glavni uzrok infertiliteta kod polovine neplodnih parova. Na genetskom nivou infertilitet kod muškaraca mogu uzrokovati hromozomske aberacije ili genske mutacije. U ovoj studiji analizirano je prisustvo i tip mikrodelecija Y hromozoma i mutacija u genu za regulator transmembranske provodljivosti u cističnoj fibrozi (CFTR) kao genetska osnova infertiliteta kod muškaraca u Srbiji. Cilj studije je bio da se analiziraju mutacije u CFTR genu i mikrodelecije Y hromozoma, kao potencijalni uzroci infertiliteta kod muškaraca u Srbiji, kao i da se testira hipoteza da su CFTR mutacije kod infertilnih muškaraca predominantno locirane u nekoliko poslednjih egzona. Metode. Studija je obuhvatila 33 muškarca sa oligo ili azospermijom. Detekcija mikrodelecija Y hromozoma u regionu faktora azospermije (AZF) vršena je pomoću multipleks PCR metode. Pretraživanje CFTR gena vršeno je metodom elektroforeze u gelu sa gradijentom denaturišućeg agensa (DGGE). Rezultati. Delecije Y hromozoma su detektovane kod četiri bolesnika, predominantno u AZFc regionu (četiri od ukupno šest). Mutacije u CFTR genu su detektovane na osam od 66 analizovanih hromozoma infertilnih muškaraca. Najčešće detektovana CFTR mutacija je F508del (šest od osam). Zaključak. Ova studija je potvrdila da mikrodelecije Y hromozoma i mutacije u CFTR genu igraju važnu ulogu u etiologiji infertiliteta kod muškaraca u Srbiji. Genetsko testiranje koje obuhvata detekciju mikrodelecija Y hromozoma i mutacija u CFTR genu uvedeno je u rutinsku dijagnostičku praksu i ponuđeno je parovima koji pristupaju asistiranoj reprodukciji. S obzirom da tip mikrodelecija Y hromozoma i tip mutacija u CFTR genu imaju prognostički značaj, preporuka je da se genotipizacija AZF regiona i CFTR gena ne vrši samo kod bolesnika sa umanjenim kvalitetom sperme pre pristupanja asistiranoj reprodukciji, već i u svrhe preimplantacione i prenatalne dijagnostike kod parova kod kojih je uspešno izvršena in vitro fertilizacija.
AB  - Background/Aim. Impaired fertility of a male partner is the main cause of infertility in up to one half of all infertile couples. At the genetic level, male infertility can be caused by chromosome aberrations or gene mutations. The presence and types of Y chromosome microdeletions and cystic fybrosis transmembrane conductance regulator (CFTR) gene mutations as genetic cause of male infertility was tested in Serbian men. The aim of this study was to analyze CFTR gene mutations and Y chromosome microdelations as potential causes of male infertility in Serbian patients, as well as to test the hypothesis that CFTR mutations in infertile men are predominantly located in the several last exons of the gene. Methods. This study has encompassed 33 men with oligo- or azoospermia. The screening for Y chromosome microdeletions in the azoospermia factor (AZF) region was performed by multiplex PCR analysis. The screening of the CFTR gene was performed by denaturing gradient gel electrophoresis (DGGE) method. Results. Deletions on Y chromosome were detected in four patients, predominantly in AZFc region (four of total six deletions). Mutations in the CFTR gene were detected on eight out of 66 analyzed chromosomes of infertile men. The most common mutation was F508del (six of total eight mutations). Conclusion. This study confirmed that both Y chromosome microdeletions and CFTR gene mutations played important role in etiology of male infertility in Serbian infertile men. Genetic testing for Y chromosome microdeletions and CFTR gene mutations has been introduced in routine diagnostics and offered to couples undergoing assisted reproduction techniques. Considering that both the type of Y chromosome microdeletion and the type of CFTR mutation have a prognostic value, it is recommended that AZF and CFTR genotyping should not only be performed in patients with reduced sperm quality before undergoing assisted reproduction, but also for the purpose of preimplantation and prenatal diagnostics in couples in which in vitro fertilization has been performed successfully.
PB  - Vojnomedicinska akademija - Institut za naučne informacije, Beograd
T2  - Vojnosanitetski pregled
T1  - Analiza mikrodelecija Y hromozoma i mutacija CFTR gena kao genetskih markera infertiliteta kod muškaraca u Srbiji
T1  - Analysis of Y chromosome microdeletions and CFTR gene mutations as genetic markers of infertility in Serbian men
EP  - 256
IS  - 4
SP  - 253
VL  - 64
DO  - 10.2298/VSP0704253D
ER  - 

@article{
author = "Dinić, Jelena and Kušić-Tišma, Jelena and Nikolić, Aleksandra and Divac Rankov, Aleksandra and Ristanović, Momčilo and Radojković, Dragica",
year = "2007",
abstract = "Uvod/Cilj. Poremećena plodnost muškog partnera je glavni uzrok infertiliteta kod polovine neplodnih parova. Na genetskom nivou infertilitet kod muškaraca mogu uzrokovati hromozomske aberacije ili genske mutacije. U ovoj studiji analizirano je prisustvo i tip mikrodelecija Y hromozoma i mutacija u genu za regulator transmembranske provodljivosti u cističnoj fibrozi (CFTR) kao genetska osnova infertiliteta kod muškaraca u Srbiji. Cilj studije je bio da se analiziraju mutacije u CFTR genu i mikrodelecije Y hromozoma, kao potencijalni uzroci infertiliteta kod muškaraca u Srbiji, kao i da se testira hipoteza da su CFTR mutacije kod infertilnih muškaraca predominantno locirane u nekoliko poslednjih egzona. Metode. Studija je obuhvatila 33 muškarca sa oligo ili azospermijom. Detekcija mikrodelecija Y hromozoma u regionu faktora azospermije (AZF) vršena je pomoću multipleks PCR metode. Pretraživanje CFTR gena vršeno je metodom elektroforeze u gelu sa gradijentom denaturišućeg agensa (DGGE). Rezultati. Delecije Y hromozoma su detektovane kod četiri bolesnika, predominantno u AZFc regionu (četiri od ukupno šest). Mutacije u CFTR genu su detektovane na osam od 66 analizovanih hromozoma infertilnih muškaraca. Najčešće detektovana CFTR mutacija je F508del (šest od osam). Zaključak. Ova studija je potvrdila da mikrodelecije Y hromozoma i mutacije u CFTR genu igraju važnu ulogu u etiologiji infertiliteta kod muškaraca u Srbiji. Genetsko testiranje koje obuhvata detekciju mikrodelecija Y hromozoma i mutacija u CFTR genu uvedeno je u rutinsku dijagnostičku praksu i ponuđeno je parovima koji pristupaju asistiranoj reprodukciji. S obzirom da tip mikrodelecija Y hromozoma i tip mutacija u CFTR genu imaju prognostički značaj, preporuka je da se genotipizacija AZF regiona i CFTR gena ne vrši samo kod bolesnika sa umanjenim kvalitetom sperme pre pristupanja asistiranoj reprodukciji, već i u svrhe preimplantacione i prenatalne dijagnostike kod parova kod kojih je uspešno izvršena in vitro fertilizacija., Background/Aim. Impaired fertility of a male partner is the main cause of infertility in up to one half of all infertile couples. At the genetic level, male infertility can be caused by chromosome aberrations or gene mutations. The presence and types of Y chromosome microdeletions and cystic fybrosis transmembrane conductance regulator (CFTR) gene mutations as genetic cause of male infertility was tested in Serbian men. The aim of this study was to analyze CFTR gene mutations and Y chromosome microdelations as potential causes of male infertility in Serbian patients, as well as to test the hypothesis that CFTR mutations in infertile men are predominantly located in the several last exons of the gene. Methods. This study has encompassed 33 men with oligo- or azoospermia. The screening for Y chromosome microdeletions in the azoospermia factor (AZF) region was performed by multiplex PCR analysis. The screening of the CFTR gene was performed by denaturing gradient gel electrophoresis (DGGE) method. Results. Deletions on Y chromosome were detected in four patients, predominantly in AZFc region (four of total six deletions). Mutations in the CFTR gene were detected on eight out of 66 analyzed chromosomes of infertile men. The most common mutation was F508del (six of total eight mutations). Conclusion. This study confirmed that both Y chromosome microdeletions and CFTR gene mutations played important role in etiology of male infertility in Serbian infertile men. Genetic testing for Y chromosome microdeletions and CFTR gene mutations has been introduced in routine diagnostics and offered to couples undergoing assisted reproduction techniques. Considering that both the type of Y chromosome microdeletion and the type of CFTR mutation have a prognostic value, it is recommended that AZF and CFTR genotyping should not only be performed in patients with reduced sperm quality before undergoing assisted reproduction, but also for the purpose of preimplantation and prenatal diagnostics in couples in which in vitro fertilization has been performed successfully.",
publisher = "Vojnomedicinska akademija - Institut za naučne informacije, Beograd",
journal = "Vojnosanitetski pregled",
title = "Analiza mikrodelecija Y hromozoma i mutacija CFTR gena kao genetskih markera infertiliteta kod muškaraca u Srbiji, Analysis of Y chromosome microdeletions and CFTR gene mutations as genetic markers of infertility in Serbian men",
pages = "256-253",
number = "4",
volume = "64",
doi = "10.2298/VSP0704253D"
}

Dinić, J., Kušić-Tišma, J., Nikolić, A., Divac Rankov, A., Ristanović, M.,& Radojković, D.. (2007). Analiza mikrodelecija Y hromozoma i mutacija CFTR gena kao genetskih markera infertiliteta kod muškaraca u Srbiji. in Vojnosanitetski pregled
Vojnomedicinska akademija - Institut za naučne informacije, Beograd., 64(4), 253-256.
https://doi.org/10.2298/VSP0704253D

Dinić J, Kušić-Tišma J, Nikolić A, Divac Rankov A, Ristanović M, Radojković D. Analiza mikrodelecija Y hromozoma i mutacija CFTR gena kao genetskih markera infertiliteta kod muškaraca u Srbiji. in Vojnosanitetski pregled. 2007;64(4):253-256.
doi:10.2298/VSP0704253D .

Dinić, Jelena, Kušić-Tišma, Jelena, Nikolić, Aleksandra, Divac Rankov, Aleksandra, Ristanović, Momčilo, Radojković, Dragica, "Analiza mikrodelecija Y hromozoma i mutacija CFTR gena kao genetskih markera infertiliteta kod muškaraca u Srbiji" in Vojnosanitetski pregled, 64, no. 4 (2007):253-256,
https://doi.org/10.2298/VSP0704253D . .

TY  - JOUR
AU  - Kušić-Tišma, Jelena
AU  - Kojić, Snežana
AU  - Divac Rankov, Aleksandra
AU  - Stefanović, D
PY  - 2005
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/236
AB  - DNA replication origins of eukaryotes lack linear replicator elements but contain short (dT)(n) (dA)(n) sequences that could build mutually equivalent unorthodox structures. Here we report that the lamin B2 origin of DNA replication adopts an alternative form characterized by unpaired regions CTTTTTTTTTTCC/GGAAAAAAAAAAG (3900-3912) and CCTTTTTTTTC/GAAAAAAAAGG (4141-4151). Both unpaired regions are resistant to DNase and except in central parts of their homopyrimidine strands are sensitive to single strand-specific chemicals. Interactions that protect central pyrimidines probably stabilize the bubble-like areas. Because DNA fragments containing either one or both bubbles migrate in TBM (89 mM Tris base, 89 mM boric acid, and 2 mM MgCl2) PAGE even faster than expected from their linear size, interacting regions are expected to belong to the same molecule. In an origin fragment containing a single bubble, free homopyrimidine strand can only interact with Hoogsteen hydrogen bonding surfaces from a complementary double stranded sequence. Indeed, this origin fragment reacts with triplex preferring antibody. In competition binding experiments control double stranded DNA or single stranded (dT) 40 do not affect origin-antibody interaction, whereas TAT and GGC triplexes exert competitive effect. Because the chosen fragment does not contain potential GGC forming sequences, these experiments confirm that the lamin B2 origin adopts a structure partly composed of intramolecular TAT triads.
PB  - Amer Soc Biochemistry Molecular Biology Inc, Bethesda
T2  - Journal of Biological Chemistry
T1  - Noncanonical DNA elements in the lamin B2 origin of DNA replication
EP  - 9854
IS  - 11
SP  - 9848
VL  - 280
DO  - 10.1074/jbc.M408310200
ER  - 

@article{
author = "Kušić-Tišma, Jelena and Kojić, Snežana and Divac Rankov, Aleksandra and Stefanović, D",
year = "2005",
abstract = "DNA replication origins of eukaryotes lack linear replicator elements but contain short (dT)(n) (dA)(n) sequences that could build mutually equivalent unorthodox structures. Here we report that the lamin B2 origin of DNA replication adopts an alternative form characterized by unpaired regions CTTTTTTTTTTCC/GGAAAAAAAAAAG (3900-3912) and CCTTTTTTTTC/GAAAAAAAAGG (4141-4151). Both unpaired regions are resistant to DNase and except in central parts of their homopyrimidine strands are sensitive to single strand-specific chemicals. Interactions that protect central pyrimidines probably stabilize the bubble-like areas. Because DNA fragments containing either one or both bubbles migrate in TBM (89 mM Tris base, 89 mM boric acid, and 2 mM MgCl2) PAGE even faster than expected from their linear size, interacting regions are expected to belong to the same molecule. In an origin fragment containing a single bubble, free homopyrimidine strand can only interact with Hoogsteen hydrogen bonding surfaces from a complementary double stranded sequence. Indeed, this origin fragment reacts with triplex preferring antibody. In competition binding experiments control double stranded DNA or single stranded (dT) 40 do not affect origin-antibody interaction, whereas TAT and GGC triplexes exert competitive effect. Because the chosen fragment does not contain potential GGC forming sequences, these experiments confirm that the lamin B2 origin adopts a structure partly composed of intramolecular TAT triads.",
publisher = "Amer Soc Biochemistry Molecular Biology Inc, Bethesda",
journal = "Journal of Biological Chemistry",
title = "Noncanonical DNA elements in the lamin B2 origin of DNA replication",
pages = "9854-9848",
number = "11",
volume = "280",
doi = "10.1074/jbc.M408310200"
}

Kušić-Tišma, J., Kojić, S., Divac Rankov, A.,& Stefanović, D.. (2005). Noncanonical DNA elements in the lamin B2 origin of DNA replication. in Journal of Biological Chemistry
Amer Soc Biochemistry Molecular Biology Inc, Bethesda., 280(11), 9848-9854.
https://doi.org/10.1074/jbc.M408310200

Kušić-Tišma J, Kojić S, Divac Rankov A, Stefanović D. Noncanonical DNA elements in the lamin B2 origin of DNA replication. in Journal of Biological Chemistry. 2005;280(11):9848-9854.
doi:10.1074/jbc.M408310200 .

Kušić-Tišma, Jelena, Kojić, Snežana, Divac Rankov, Aleksandra, Stefanović, D, "Noncanonical DNA elements in the lamin B2 origin of DNA replication" in Journal of Biological Chemistry, 280, no. 11 (2005):9848-9854,
https://doi.org/10.1074/jbc.M408310200 . .

TY  - THES
AU  - Kušić, Jelena
PY  - 2005
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=1967
UR  - https://nardus.mpn.gov.rs/handle/123456789/2171
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:9710/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=31423759
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/8
AB  - Inicijacija replikacije DNK kod eukariota započinje vezivanjem proteinskog kompleksa ORC za diskretna mesta u genomu nazvana ori-sekvence ili ori. Specifične sekvence odgovome za prepoznavanje i vezivanje kompleksa ORC, kao i mehanizam kojim ORC selektuje orisekvence još uvek nisu poznati. Jedna od malobrojnih zajedničkih karakteristika mesta uključenih u vezivanje inicijacionog proteina jeste visok sadržaj AT bp i kratkih nizova (dA)-(dT) što ukazuje na mogućnost da ori-sekvence obrazuju sinonimne stmkture koje odreduju specifičnost vezivanja inicijacionog proteina. Radi testiranja ove pretpostavke, analizirana je struktura i oblik humane ori-sekvence lamin B2 i detaljno ispitana DNK vezivna specifičnost proteina HsOrc4. Ovaj protein predstavlja jednu od subjedinica kompleksa ORC i pokazuje istu DNK-vezivnu aktivnost kao i kompleks ORC. Utvrđeno je da ori-sekvenca, pod uslovima neutralnog pH, niske ili umerene jonske jačine i u prisustvu jona Mg2+ zauzima altemativnu formu koju karakteriše prisustvo denaturisanog regiona, okceta, i povećana elektroforetska pokretljivost u nativnoj PAGE. Stabilno prisustvo denaturisanog regiona u okviru fragmenta DNK omogućeno je formiranjem Hoogsteen-ovih vodoničnih veza izmedu centralnih pirimidina okceta i adenina jednog od kratkih nizova (dA)-(dT). Kao rezultat ove interakcije nastaje dvolančana petlja koja u osnovi sadrži intramolekulski tripleks. Struktura intramolekulskog tripleksa formira se u regionu koji interaguje sa inicijacionim proteinom i može predstavljati jedan od elemenata odgovornih za prepoznavanje i vezivanje ovog proteina. U eksperimentima direktnog vezivanja proteina HsOrc4 utvrdeno je da on ne prepoznaje kratke nizove (dA)-(dT) i (dA), dok se za (dT) slabo vezuje. Najveći afmitet protein je pokazivao za trolančane strukture tipa TAT. Kompeticija jedno-, dvo- i trolančanih molekula DNK vezivanju HsOrc4 za ori-sekvencu pokazala je da protein razlikuje trolančanu strukturu od jedno- i dvolančane i specifično se vezuje za nju. Sudeći po efikasnosti kompeticije, trolančana DNK bila je veoma slična prirodnim vezivnim mestima proteina HsOrc4. Svojstvo ori-sekvence da formira intramolekulski tripleks i specifično vezivanje proteina HsOrc4 za tripleks sugeriše da trolančana struktura može predstavljati deo mehanizma kojim inicijacioni protein prepoznaje i selektuje mesta inicijacije replikacije.
AB  - In complex eukaryotes DNA replication is initiated by binding of origin recognition complexes (ORCs) to specific genomic sites called origins of replication. Consensus sequence required for this event and the mechanism by which ORC is localized to origins of replication remain poorly understood. General features of genomic regions involved in initiator protein binding are AT-richness and frequent occurrence of short (dA)-(dT) runs. Such distribution of A and T residues opens a possibility that origins of replication build mutually equivalent unorthodox structures which are recognised by initiation protein. In order to test this hypothesis, a study of structure and shape of the human lamin B2 origin was performed. DNA binding activity of protein HsOrc4, one of ORCs subunits that exhibited similar DNA binding properties as the whole complex, was also tested. It was shown that, at neutral pH, low or moderate ionic strength and in presence of Mg" ions, lamin B2 ongm adopted alternative helical form, characterized by a single unpaired region and faster migration in native polyacrylamide geis. It was proposed that these properties reflected the ability of origin DNA to form double stranded loop with intramolecular triplex in its base. Triplex was kept together by Hoogsteen hydrogen bonding between Central pyrimidines of unpaired region and complementary double stranded sequence. Since intramolecular noncanonical structure formed in origin sequences protected by ORC in vivo and in vitro, it could represent the element responsible for site-specific ORC binding. In order to test this notion, binding specificity of HsOrc4 was tested in direct and competition DNA binding experiments. The protein did not recognize (dA) or (dA)-(dT), but it exhibited very low affmity for (dT) and a very high affmity for TAT triplex. Consistent with that, triple stranded DNA competed very well with origin DNA for HsOrc4 binding, whereas single or double stranded DNA exhibited much less significant competitive effect. As judged by its competitive efficiency, triple stranded DNA was very similar to naturally ocuring DNA binding sites of HsOrc4. In conclusion, formation o f intramolecular triplex within origin DNA and its specific recognition by HsOrc4 suggest that triple stranded structure might play a role in selection of eukaryotic origins of replication.
PB  - Univerzitet u Beogradu, Biološki fakultet
T1  - Interakcija inicijacionog proteina ORC sa replikatorom regiona lamin B2
T1  - Interaction of initiation protein Orc with lamin B2 replication region
UR  - https://hdl.handle.net/21.15107/rcub_nardus_2171
ER  - 

@phdthesis{
author = "Kušić, Jelena",
year = "2005",
abstract = "Inicijacija replikacije DNK kod eukariota započinje vezivanjem proteinskog kompleksa ORC za diskretna mesta u genomu nazvana ori-sekvence ili ori. Specifične sekvence odgovome za prepoznavanje i vezivanje kompleksa ORC, kao i mehanizam kojim ORC selektuje orisekvence još uvek nisu poznati. Jedna od malobrojnih zajedničkih karakteristika mesta uključenih u vezivanje inicijacionog proteina jeste visok sadržaj AT bp i kratkih nizova (dA)-(dT) što ukazuje na mogućnost da ori-sekvence obrazuju sinonimne stmkture koje odreduju specifičnost vezivanja inicijacionog proteina. Radi testiranja ove pretpostavke, analizirana je struktura i oblik humane ori-sekvence lamin B2 i detaljno ispitana DNK vezivna specifičnost proteina HsOrc4. Ovaj protein predstavlja jednu od subjedinica kompleksa ORC i pokazuje istu DNK-vezivnu aktivnost kao i kompleks ORC. Utvrđeno je da ori-sekvenca, pod uslovima neutralnog pH, niske ili umerene jonske jačine i u prisustvu jona Mg2+ zauzima altemativnu formu koju karakteriše prisustvo denaturisanog regiona, okceta, i povećana elektroforetska pokretljivost u nativnoj PAGE. Stabilno prisustvo denaturisanog regiona u okviru fragmenta DNK omogućeno je formiranjem Hoogsteen-ovih vodoničnih veza izmedu centralnih pirimidina okceta i adenina jednog od kratkih nizova (dA)-(dT). Kao rezultat ove interakcije nastaje dvolančana petlja koja u osnovi sadrži intramolekulski tripleks. Struktura intramolekulskog tripleksa formira se u regionu koji interaguje sa inicijacionim proteinom i može predstavljati jedan od elemenata odgovornih za prepoznavanje i vezivanje ovog proteina. U eksperimentima direktnog vezivanja proteina HsOrc4 utvrdeno je da on ne prepoznaje kratke nizove (dA)-(dT) i (dA), dok se za (dT) slabo vezuje. Najveći afmitet protein je pokazivao za trolančane strukture tipa TAT. Kompeticija jedno-, dvo- i trolančanih molekula DNK vezivanju HsOrc4 za ori-sekvencu pokazala je da protein razlikuje trolančanu strukturu od jedno- i dvolančane i specifično se vezuje za nju. Sudeći po efikasnosti kompeticije, trolančana DNK bila je veoma slična prirodnim vezivnim mestima proteina HsOrc4. Svojstvo ori-sekvence da formira intramolekulski tripleks i specifično vezivanje proteina HsOrc4 za tripleks sugeriše da trolančana struktura može predstavljati deo mehanizma kojim inicijacioni protein prepoznaje i selektuje mesta inicijacije replikacije., In complex eukaryotes DNA replication is initiated by binding of origin recognition complexes (ORCs) to specific genomic sites called origins of replication. Consensus sequence required for this event and the mechanism by which ORC is localized to origins of replication remain poorly understood. General features of genomic regions involved in initiator protein binding are AT-richness and frequent occurrence of short (dA)-(dT) runs. Such distribution of A and T residues opens a possibility that origins of replication build mutually equivalent unorthodox structures which are recognised by initiation protein. In order to test this hypothesis, a study of structure and shape of the human lamin B2 origin was performed. DNA binding activity of protein HsOrc4, one of ORCs subunits that exhibited similar DNA binding properties as the whole complex, was also tested. It was shown that, at neutral pH, low or moderate ionic strength and in presence of Mg" ions, lamin B2 ongm adopted alternative helical form, characterized by a single unpaired region and faster migration in native polyacrylamide geis. It was proposed that these properties reflected the ability of origin DNA to form double stranded loop with intramolecular triplex in its base. Triplex was kept together by Hoogsteen hydrogen bonding between Central pyrimidines of unpaired region and complementary double stranded sequence. Since intramolecular noncanonical structure formed in origin sequences protected by ORC in vivo and in vitro, it could represent the element responsible for site-specific ORC binding. In order to test this notion, binding specificity of HsOrc4 was tested in direct and competition DNA binding experiments. The protein did not recognize (dA) or (dA)-(dT), but it exhibited very low affmity for (dT) and a very high affmity for TAT triplex. Consistent with that, triple stranded DNA competed very well with origin DNA for HsOrc4 binding, whereas single or double stranded DNA exhibited much less significant competitive effect. As judged by its competitive efficiency, triple stranded DNA was very similar to naturally ocuring DNA binding sites of HsOrc4. In conclusion, formation o f intramolecular triplex within origin DNA and its specific recognition by HsOrc4 suggest that triple stranded structure might play a role in selection of eukaryotic origins of replication.",
publisher = "Univerzitet u Beogradu, Biološki fakultet",
title = "Interakcija inicijacionog proteina ORC sa replikatorom regiona lamin B2, Interaction of initiation protein Orc with lamin B2 replication region",
url = "https://hdl.handle.net/21.15107/rcub_nardus_2171"
}

Kušić, J.. (2005). Interakcija inicijacionog proteina ORC sa replikatorom regiona lamin B2. 
Univerzitet u Beogradu, Biološki fakultet..
https://hdl.handle.net/21.15107/rcub_nardus_2171

Kušić J. Interakcija inicijacionog proteina ORC sa replikatorom regiona lamin B2. 2005;.
https://hdl.handle.net/21.15107/rcub_nardus_2171 .

Kušić, Jelena, "Interakcija inicijacionog proteina ORC sa replikatorom regiona lamin B2" (2005),
https://hdl.handle.net/21.15107/rcub_nardus_2171 .

TY  - JOUR
AU  - Kušić-Tišma, Jelena
AU  - Radojković, Dragica 
AU  - Maletić-Vukotić, Vinka D.
AU  - Branković, Snežana
AU  - Savić, Ana P.
PY  - 2002
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/167
AB  - Do sada je otkriven veliki broj gena koji, kada su mutirani ili deletirani uzrokuju promene u muškom reprodukcionom sistemu. Opstrukciona azospermija, koja je uzrok infertiliteta, u šest posto slučajeva posledica je kongenitalnog nedostatka vaza deferensa. Takođe, kongenitalni nedostatak vaza deferensa se javlja kod 95 posto muškaraca obolelih od cistične fibroze, koja nastaje usled mutacija u genu CFTR. Novija istraživanja pokazuju da je kod muškaraca infertilnih usled kongenitalnog nedostatka vaza deferensa, bez kliničkih znakova cistične fibroze, povećana učestalost mutacija u genu CFTR u odnosu na učestalost mutiranog gena CFTR u opštoj populaciji. Pošto je kod muškaraca obolelih od cistične fibroze nađen širok spektar oštećenja reprodukcionog trakta odlučili smo se za analizu mutacija i polimorfizama u genu CFTR kod muškaraca, infertilnih usled oligospermije ili azospermije, radi rasvetljavanja moguće uloge gena CFTR u patogenezi infertilnosti muškaraca. U grupi osoba s opstrukcionom azospermijom otkrili smo statistički značajno veću učestalost mutacija u genu CFTR nego u opštoj populaciji, što ukazuje na njegovo učešće u patologiji infertilnosti kod ove trupe ispitanika. U grupi muškaraca s poremećajem u spermatogenezi ili sazrevanju sperme učestalost mutacija u genu CFTR takođe je bila veća nego u opštoj populaciji, ali niža nego kod ispitanika s opstrukcionom azospermijom. Ovo ukazuje na veće učešće drugih gena u procesu spermatogeneze nego kod opstrukcione azospermije. S obzirom da je kod muškaraca infertilnih usled opstrukcione azospermije veća učestalost mutacija u genu CFTR, oni su s većim rizikom za rađanje deteta s cističnom fibrozom, te je kod njih indikovana analiza mutacija u ovom genu pre pristupanja asistiranoj reprodukciji.
AB  - We concluded that CFTR gene plays a role in the etiology of obstructive azoospermia and that it also could be involved in same cases of impaired spermatogenesis and sperm maturation. Due to the high incidence of CFRT mutations in patients with obstructive azoospermia we suggest screening of CFRT mutations before assisted reproduction.
PB  - Srpsko lekarsko društvo, Beograd
T2  - Srpski arhiv za celokupno lekarstvo
T1  - Mutacije i polimorfizmi u genu CFRT kod infertilnih muškaraca s oligospermijom ili azospermijom
T1  - Screening of mutations and polymorphism in CFRT gene in men infertile due to oligo- or azospermia
EP  - 6
IS  - 1-2
SP  - 1
VL  - 130
DO  - 10.2298/SARH0202001K
ER  - 

@article{
author = "Kušić-Tišma, Jelena and Radojković, Dragica  and Maletić-Vukotić, Vinka D. and Branković, Snežana and Savić, Ana P.",
year = "2002",
abstract = "Do sada je otkriven veliki broj gena koji, kada su mutirani ili deletirani uzrokuju promene u muškom reprodukcionom sistemu. Opstrukciona azospermija, koja je uzrok infertiliteta, u šest posto slučajeva posledica je kongenitalnog nedostatka vaza deferensa. Takođe, kongenitalni nedostatak vaza deferensa se javlja kod 95 posto muškaraca obolelih od cistične fibroze, koja nastaje usled mutacija u genu CFTR. Novija istraživanja pokazuju da je kod muškaraca infertilnih usled kongenitalnog nedostatka vaza deferensa, bez kliničkih znakova cistične fibroze, povećana učestalost mutacija u genu CFTR u odnosu na učestalost mutiranog gena CFTR u opštoj populaciji. Pošto je kod muškaraca obolelih od cistične fibroze nađen širok spektar oštećenja reprodukcionog trakta odlučili smo se za analizu mutacija i polimorfizama u genu CFTR kod muškaraca, infertilnih usled oligospermije ili azospermije, radi rasvetljavanja moguće uloge gena CFTR u patogenezi infertilnosti muškaraca. U grupi osoba s opstrukcionom azospermijom otkrili smo statistički značajno veću učestalost mutacija u genu CFTR nego u opštoj populaciji, što ukazuje na njegovo učešće u patologiji infertilnosti kod ove trupe ispitanika. U grupi muškaraca s poremećajem u spermatogenezi ili sazrevanju sperme učestalost mutacija u genu CFTR takođe je bila veća nego u opštoj populaciji, ali niža nego kod ispitanika s opstrukcionom azospermijom. Ovo ukazuje na veće učešće drugih gena u procesu spermatogeneze nego kod opstrukcione azospermije. S obzirom da je kod muškaraca infertilnih usled opstrukcione azospermije veća učestalost mutacija u genu CFTR, oni su s većim rizikom za rađanje deteta s cističnom fibrozom, te je kod njih indikovana analiza mutacija u ovom genu pre pristupanja asistiranoj reprodukciji., We concluded that CFTR gene plays a role in the etiology of obstructive azoospermia and that it also could be involved in same cases of impaired spermatogenesis and sperm maturation. Due to the high incidence of CFRT mutations in patients with obstructive azoospermia we suggest screening of CFRT mutations before assisted reproduction.",
publisher = "Srpsko lekarsko društvo, Beograd",
journal = "Srpski arhiv za celokupno lekarstvo",
title = "Mutacije i polimorfizmi u genu CFRT kod infertilnih muškaraca s oligospermijom ili azospermijom, Screening of mutations and polymorphism in CFRT gene in men infertile due to oligo- or azospermia",
pages = "6-1",
number = "1-2",
volume = "130",
doi = "10.2298/SARH0202001K"
}

Kušić-Tišma, J., Radojković, D., Maletić-Vukotić, V. D., Branković, S.,& Savić, A. P.. (2002). Mutacije i polimorfizmi u genu CFRT kod infertilnih muškaraca s oligospermijom ili azospermijom. in Srpski arhiv za celokupno lekarstvo
Srpsko lekarsko društvo, Beograd., 130(1-2), 1-6.
https://doi.org/10.2298/SARH0202001K

Kušić-Tišma J, Radojković D, Maletić-Vukotić VD, Branković S, Savić AP. Mutacije i polimorfizmi u genu CFRT kod infertilnih muškaraca s oligospermijom ili azospermijom. in Srpski arhiv za celokupno lekarstvo. 2002;130(1-2):1-6.
doi:10.2298/SARH0202001K .

Kušić-Tišma, Jelena, Radojković, Dragica , Maletić-Vukotić, Vinka D., Branković, Snežana, Savić, Ana P., "Mutacije i polimorfizmi u genu CFRT kod infertilnih muškaraca s oligospermijom ili azospermijom" in Srpski arhiv za celokupno lekarstvo, 130, no. 1-2 (2002):1-6,
https://doi.org/10.2298/SARH0202001K . .

TY  - CONF
AU  - Nikolić, Aleksandra
AU  - Kušić-Tišma, Jelena
AU  - Radojković, Dragica
AU  - Lukić, S
AU  - Milosavljević, T
AU  - Savić, A
PY  - 2002
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/166
PB  - Springernature, London
C3  - European Journal of Human Genetics
T1  - Screening for CFTR gene mutations and polymorphisms in patients with chronic pancreatitis
EP  - 136
SP  - 136
VL  - 10
UR  - https://hdl.handle.net/21.15107/rcub_imagine_166
ER  - 

@conference{
author = "Nikolić, Aleksandra and Kušić-Tišma, Jelena and Radojković, Dragica and Lukić, S and Milosavljević, T and Savić, A",
year = "2002",
publisher = "Springernature, London",
journal = "European Journal of Human Genetics",
title = "Screening for CFTR gene mutations and polymorphisms in patients with chronic pancreatitis",
pages = "136-136",
volume = "10",
url = "https://hdl.handle.net/21.15107/rcub_imagine_166"
}

Nikolić, A., Kušić-Tišma, J., Radojković, D., Lukić, S., Milosavljević, T.,& Savić, A.. (2002). Screening for CFTR gene mutations and polymorphisms in patients with chronic pancreatitis. in European Journal of Human Genetics
Springernature, London., 10, 136-136.
https://hdl.handle.net/21.15107/rcub_imagine_166

Nikolić A, Kušić-Tišma J, Radojković D, Lukić S, Milosavljević T, Savić A. Screening for CFTR gene mutations and polymorphisms in patients with chronic pancreatitis. in European Journal of Human Genetics. 2002;10:136-136.
https://hdl.handle.net/21.15107/rcub_imagine_166 .

Nikolić, Aleksandra, Kušić-Tišma, Jelena, Radojković, Dragica, Lukić, S, Milosavljević, T, Savić, A, "Screening for CFTR gene mutations and polymorphisms in patients with chronic pancreatitis" in European Journal of Human Genetics, 10 (2002):136-136,
https://hdl.handle.net/21.15107/rcub_imagine_166 .

TY  - JOUR
AU  - Tomić, J.
AU  - Radojković, Dragica
AU  - Kušić-Tišma, Jelena
AU  - Jovanović, Milija
AU  - Vijatov, G.
PY  - 2001
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/153
AB  - Cystic fibrosis (CF) is an autosomal recessive disease. The gene responsible for cystic fibrosis is located on the long arm of chromosome 7 (7q31) and it carries information for CFTR protein (Cystic Fibrosis Conductance Regulator Protein). This protein is located in the epithelial cell membrane and contributes in chloride transportation. More than 800 mutations have been discovered in CFTR gene by now. The most frequent mutation is deletion of 3 bp in exon 10, which leads to absence of phenylalanine on position ΔF508 in the protein and is marked as 508. In our paper 3 patients (2 male and 1 female children) with CF are presented. We analyzed the presence of mutations in CFTR gene in our patients and the members of their families. DNA was isolated from peripheral blood lymhocytes of our patients and members of their families. Using direct diagnostic methods, the presence of the following mutations has been determined. ΔF508 - by heteroduplex method, G551D and R553X by polymorphism length restriction fragments analysis, G542X, N1303K, 621 + 1GAT, R117X by method of specific PCR mutagenesis. We analyzed exons 4, 10 and 21 within CFTR gene by indirect diagnostics - DGGE (denaturating gradient gel electrophoresis). Automatic sequencing identifies the changes noticed in these exons. The female patient with a respiratory form of the disease is mixed heterozygote for N103K and 525delT mutations. Her father and sister are heterozygous for N1303K mutation and mother is heterozygous for 525delT mutation. These two types of mutations carried by our parents seriously damage the function of CFTR protein processing. 525delT is a "de novo" mutation and has still not been describe on functional level. It is assumed to lead to the absence of CFTR protein synthesis. Today, prenatal genotype diagnosis of CF from trophoblasts is possible. By using prenatal genotype diagnosis CF has been excluded in our female patient's younger sister.
PB  - KBC "Dr Dragiša Mišović" - Centar za dečje plućne bolesti i tuberkulozu, Beograd
T2  - Children's Pulmonology
T1  - Genetic aspect of cystic fibrosis [Genetski aspekt cistične fibroze]
EP  - 67
IS  - 1-2
SP  - 63
VL  - 9
UR  - https://hdl.handle.net/21.15107/rcub_imagine_153
ER  - 

@article{
author = "Tomić, J. and Radojković, Dragica and Kušić-Tišma, Jelena and Jovanović, Milija and Vijatov, G.",
year = "2001",
abstract = "Cystic fibrosis (CF) is an autosomal recessive disease. The gene responsible for cystic fibrosis is located on the long arm of chromosome 7 (7q31) and it carries information for CFTR protein (Cystic Fibrosis Conductance Regulator Protein). This protein is located in the epithelial cell membrane and contributes in chloride transportation. More than 800 mutations have been discovered in CFTR gene by now. The most frequent mutation is deletion of 3 bp in exon 10, which leads to absence of phenylalanine on position ΔF508 in the protein and is marked as 508. In our paper 3 patients (2 male and 1 female children) with CF are presented. We analyzed the presence of mutations in CFTR gene in our patients and the members of their families. DNA was isolated from peripheral blood lymhocytes of our patients and members of their families. Using direct diagnostic methods, the presence of the following mutations has been determined. ΔF508 - by heteroduplex method, G551D and R553X by polymorphism length restriction fragments analysis, G542X, N1303K, 621 + 1GAT, R117X by method of specific PCR mutagenesis. We analyzed exons 4, 10 and 21 within CFTR gene by indirect diagnostics - DGGE (denaturating gradient gel electrophoresis). Automatic sequencing identifies the changes noticed in these exons. The female patient with a respiratory form of the disease is mixed heterozygote for N103K and 525delT mutations. Her father and sister are heterozygous for N1303K mutation and mother is heterozygous for 525delT mutation. These two types of mutations carried by our parents seriously damage the function of CFTR protein processing. 525delT is a "de novo" mutation and has still not been describe on functional level. It is assumed to lead to the absence of CFTR protein synthesis. Today, prenatal genotype diagnosis of CF from trophoblasts is possible. By using prenatal genotype diagnosis CF has been excluded in our female patient's younger sister.",
publisher = "KBC "Dr Dragiša Mišović" - Centar za dečje plućne bolesti i tuberkulozu, Beograd",
journal = "Children's Pulmonology",
title = "Genetic aspect of cystic fibrosis [Genetski aspekt cistične fibroze]",
pages = "67-63",
number = "1-2",
volume = "9",
url = "https://hdl.handle.net/21.15107/rcub_imagine_153"
}

Tomić, J., Radojković, D., Kušić-Tišma, J., Jovanović, M.,& Vijatov, G.. (2001). Genetic aspect of cystic fibrosis [Genetski aspekt cistične fibroze]. in Children's Pulmonology
KBC "Dr Dragiša Mišović" - Centar za dečje plućne bolesti i tuberkulozu, Beograd., 9(1-2), 63-67.
https://hdl.handle.net/21.15107/rcub_imagine_153

Tomić J, Radojković D, Kušić-Tišma J, Jovanović M, Vijatov G. Genetic aspect of cystic fibrosis [Genetski aspekt cistične fibroze]. in Children's Pulmonology. 2001;9(1-2):63-67.
https://hdl.handle.net/21.15107/rcub_imagine_153 .

Tomić, J., Radojković, Dragica, Kušić-Tišma, Jelena, Jovanović, Milija, Vijatov, G., "Genetic aspect of cystic fibrosis [Genetski aspekt cistične fibroze]" in Children's Pulmonology, 9, no. 1-2 (2001):63-67,
https://hdl.handle.net/21.15107/rcub_imagine_153 .

TY  - JOUR
AU  - Nikolić, Aleksandra
AU  - Divac Rankov, Aleksandra
AU  - Kušić-Tišma, Jelena
AU  - Savić, A.
PY  - 2001
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/154
AB  - More than 100 sequence polymorphisms have been identified in the CFTR gene thus far. Routine molecular diagnostic methods are aimed at the detection of the most common mutations in the CFTR gene; these do not usually include polymorphisms. Consequently, there is little data about polymorphism frequency in European populations, and there is no data at all for the Yugoslav population. Therefore, the effects of CFTR polymorphisms are not known. Conclusions about their role can be drawn from genotype-phenotype studies. The aim of this study was to determine the frequency of the 2694T/G polymorphism in a healthy Yugoslav population (control group), patients with congenital bilateral absence of vas deferens (CBAVD) and patients with chronic pancreatitis (CP). Frequencies of 2694T and 2694G alleles obtained in the healthy group were 71 and 29%, respectively; these are the first data of CFTR polymorphism frequencies in Yugoslavia. Frequencies of the 2694G allele in CBAVD patients (25%) and CP patients (26%) were similar to the frequency obtained for the healthy population (29%), leading to the conclusion that the presence of this polymorphism is not associated with these CFTR-related monosymptomatic disorders.
PB  - Macedonian Academy Of Sciences And Arts
T2  - Balkan Journal of Medical Genetics
T1  - Frequency of the CFTR 2694T/G polymorphism and its association with CFTR-related monosymptomatic disorders
EP  - 46
IS  - 1-2
SP  - 43
VL  - 4
UR  - https://hdl.handle.net/21.15107/rcub_imagine_154
ER  - 

@article{
author = "Nikolić, Aleksandra and Divac Rankov, Aleksandra and Kušić-Tišma, Jelena and Savić, A.",
year = "2001",
abstract = "More than 100 sequence polymorphisms have been identified in the CFTR gene thus far. Routine molecular diagnostic methods are aimed at the detection of the most common mutations in the CFTR gene; these do not usually include polymorphisms. Consequently, there is little data about polymorphism frequency in European populations, and there is no data at all for the Yugoslav population. Therefore, the effects of CFTR polymorphisms are not known. Conclusions about their role can be drawn from genotype-phenotype studies. The aim of this study was to determine the frequency of the 2694T/G polymorphism in a healthy Yugoslav population (control group), patients with congenital bilateral absence of vas deferens (CBAVD) and patients with chronic pancreatitis (CP). Frequencies of 2694T and 2694G alleles obtained in the healthy group were 71 and 29%, respectively; these are the first data of CFTR polymorphism frequencies in Yugoslavia. Frequencies of the 2694G allele in CBAVD patients (25%) and CP patients (26%) were similar to the frequency obtained for the healthy population (29%), leading to the conclusion that the presence of this polymorphism is not associated with these CFTR-related monosymptomatic disorders.",
publisher = "Macedonian Academy Of Sciences And Arts",
journal = "Balkan Journal of Medical Genetics",
title = "Frequency of the CFTR 2694T/G polymorphism and its association with CFTR-related monosymptomatic disorders",
pages = "46-43",
number = "1-2",
volume = "4",
url = "https://hdl.handle.net/21.15107/rcub_imagine_154"
}

Nikolić, A., Divac Rankov, A., Kušić-Tišma, J.,& Savić, A.. (2001). Frequency of the CFTR 2694T/G polymorphism and its association with CFTR-related monosymptomatic disorders. in Balkan Journal of Medical Genetics
Macedonian Academy Of Sciences And Arts., 4(1-2), 43-46.
https://hdl.handle.net/21.15107/rcub_imagine_154

Nikolić A, Divac Rankov A, Kušić-Tišma J, Savić A. Frequency of the CFTR 2694T/G polymorphism and its association with CFTR-related monosymptomatic disorders. in Balkan Journal of Medical Genetics. 2001;4(1-2):43-46.
https://hdl.handle.net/21.15107/rcub_imagine_154 .

Nikolić, Aleksandra, Divac Rankov, Aleksandra, Kušić-Tišma, Jelena, Savić, A., "Frequency of the CFTR 2694T/G polymorphism and its association with CFTR-related monosymptomatic disorders" in Balkan Journal of Medical Genetics, 4, no. 1-2 (2001):43-46,
https://hdl.handle.net/21.15107/rcub_imagine_154 .