TY  - JOUR
AU  - Tafrali, Christina
AU  - Paizi, Arsinoi
AU  - Borg, Joseph
AU  - Radmilović Milena
AU  - Bartsakoulia, Marina
AU  - Giannopoulou, Emily
AU  - Giannakopoulou, Olga
AU  - Stojiljković, Maja
AU  - Zukić, Branka
AU  - Poulas, Konstantinos
AU  - Stavrou, Eleana F.
AU  - Lambropoulou, Polyxeni
AU  - Kourakli, Alexandra
AU  - Felice, Alexander E.
AU  - Papachatzopoulou, Adamantia
AU  - Philipsen, Sjaak
AU  - Pavlović, Sonja
AU  - Georgitsi, Marianthi
AU  - Patrinos, George P.
PY  - 2013
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/640
AB  - Aim: In this study we explored the association between genetic variations in MAP3K5 and PDE7B genes, residing on chromosome 6q23, and disease severity in beta-hemoglobinopathy patients, as well as the association between these variants with response to hydroxyurea (HU) treatment. Furthermore, we examined MAP3K5 expression in the context of high fetal hemoglobin (HbF) and upon HU treatment in erythroid progenitor cells from healthy and KLF1 haploinsufficient individuals. Materials & methods: For this purpose, we genotyped beta-thalassemia intermedia and major patients and healthy controls, as well as a cohort of compound heterozygous sickle cell disease/beta-thalassemia patients receiving HU as HbF augmentation treatment. Furthermore, we examined MAP3K5 expression in the context of high HbF and upon HU treatment in erythroid progenitor cells from healthy and KLF1 haploinsufficient individuals. Results: A short tandem repeat in the MAP3K5 promoter and two intronic MAP3K5 gene variants, as well as a PDE7B variant, are associated with low HbF levels and a severe disease phenotype. Moreover, MAP3K5 mRNA expression levels are altered in the context of high HbF and are affected by the presence of HU. Lastly, the above-mentioned MAP3K5 variants are associated with HU treatment efficacy. Conclusion: Our data suggest that these MAP3K5 variants are indicative of b-thalassemia disease severity and response to HU treatment.
PB  - Future Medicine Ltd, London
T2  - Pharmacogenomics
T1  - Genomic variation in the MAP3K5 gene is associated with beta-thalassemia disease severity and hydroxyurea treatment efficacy
EP  - 483
IS  - 5
SP  - 469
VL  - 14
DO  - 10.2217/PGS.13.31
ER  - 

@article{
author = "Tafrali, Christina and Paizi, Arsinoi and Borg, Joseph and Radmilović Milena and Bartsakoulia, Marina and Giannopoulou, Emily and Giannakopoulou, Olga and Stojiljković, Maja and Zukić, Branka and Poulas, Konstantinos and Stavrou, Eleana F. and Lambropoulou, Polyxeni and Kourakli, Alexandra and Felice, Alexander E. and Papachatzopoulou, Adamantia and Philipsen, Sjaak and Pavlović, Sonja and Georgitsi, Marianthi and Patrinos, George P.",
year = "2013",
abstract = "Aim: In this study we explored the association between genetic variations in MAP3K5 and PDE7B genes, residing on chromosome 6q23, and disease severity in beta-hemoglobinopathy patients, as well as the association between these variants with response to hydroxyurea (HU) treatment. Furthermore, we examined MAP3K5 expression in the context of high fetal hemoglobin (HbF) and upon HU treatment in erythroid progenitor cells from healthy and KLF1 haploinsufficient individuals. Materials & methods: For this purpose, we genotyped beta-thalassemia intermedia and major patients and healthy controls, as well as a cohort of compound heterozygous sickle cell disease/beta-thalassemia patients receiving HU as HbF augmentation treatment. Furthermore, we examined MAP3K5 expression in the context of high HbF and upon HU treatment in erythroid progenitor cells from healthy and KLF1 haploinsufficient individuals. Results: A short tandem repeat in the MAP3K5 promoter and two intronic MAP3K5 gene variants, as well as a PDE7B variant, are associated with low HbF levels and a severe disease phenotype. Moreover, MAP3K5 mRNA expression levels are altered in the context of high HbF and are affected by the presence of HU. Lastly, the above-mentioned MAP3K5 variants are associated with HU treatment efficacy. Conclusion: Our data suggest that these MAP3K5 variants are indicative of b-thalassemia disease severity and response to HU treatment.",
publisher = "Future Medicine Ltd, London",
journal = "Pharmacogenomics",
title = "Genomic variation in the MAP3K5 gene is associated with beta-thalassemia disease severity and hydroxyurea treatment efficacy",
pages = "483-469",
number = "5",
volume = "14",
doi = "10.2217/PGS.13.31"
}

Tafrali, C., Paizi, A., Borg, J., Radmilović Milena, Bartsakoulia, M., Giannopoulou, E., Giannakopoulou, O., Stojiljković, M., Zukić, B., Poulas, K., Stavrou, E. F., Lambropoulou, P., Kourakli, A., Felice, A. E., Papachatzopoulou, A., Philipsen, S., Pavlović, S., Georgitsi, M.,& Patrinos, G. P.. (2013). Genomic variation in the MAP3K5 gene is associated with beta-thalassemia disease severity and hydroxyurea treatment efficacy. in Pharmacogenomics
Future Medicine Ltd, London., 14(5), 469-483.
https://doi.org/10.2217/PGS.13.31

Tafrali C, Paizi A, Borg J, Radmilović Milena, Bartsakoulia M, Giannopoulou E, Giannakopoulou O, Stojiljković M, Zukić B, Poulas K, Stavrou EF, Lambropoulou P, Kourakli A, Felice AE, Papachatzopoulou A, Philipsen S, Pavlović S, Georgitsi M, Patrinos GP. Genomic variation in the MAP3K5 gene is associated with beta-thalassemia disease severity and hydroxyurea treatment efficacy. in Pharmacogenomics. 2013;14(5):469-483.
doi:10.2217/PGS.13.31 .

Tafrali, Christina, Paizi, Arsinoi, Borg, Joseph, Radmilović Milena, Bartsakoulia, Marina, Giannopoulou, Emily, Giannakopoulou, Olga, Stojiljković, Maja, Zukić, Branka, Poulas, Konstantinos, Stavrou, Eleana F., Lambropoulou, Polyxeni, Kourakli, Alexandra, Felice, Alexander E., Papachatzopoulou, Adamantia, Philipsen, Sjaak, Pavlović, Sonja, Georgitsi, Marianthi, Patrinos, George P., "Genomic variation in the MAP3K5 gene is associated with beta-thalassemia disease severity and hydroxyurea treatment efficacy" in Pharmacogenomics, 14, no. 5 (2013):469-483,
https://doi.org/10.2217/PGS.13.31 . .

TY  - JOUR
AU  - Giardine, Belinda
AU  - Borg, Joseph
AU  - Higgs, Douglas R.
AU  - Peterson, Kenneth R.
AU  - Philipsen, Sjaak
AU  - Maglott, Donna
AU  - Singleton, Belinda K.
AU  - Anstee, David J.
AU  - Basak, A. Nazli
AU  - Clark, Barnaby
AU  - Costa, Flavia C.
AU  - Faustino, Paula
AU  - Fedosyuk, Halyna
AU  - Felice, Alex E.
AU  - Francina, Alain
AU  - Galanello, Renzo
AU  - Gallivan, Monica V. E.
AU  - Georgitsi, Marianthi
AU  - Gibbons, Richard J.
AU  - Giordano, Piero C.
AU  - Harteveld, Cornelis L.
AU  - Hoyer, James D.
AU  - Jarvis, Martin
AU  - Joly, Philippe
AU  - Kanavakis, Emmanuel
AU  - Kollia, Panagoula
AU  - Menzel, Stephan
AU  - Miller, Webb
AU  - Moradkhani, Kamran
AU  - Old, John
AU  - Papachatzopoulou, Adamantia
AU  - Papadakis, Manoussos N.
AU  - Papadopoulos, Petros
AU  - Pavlović, Sonja
AU  - Perseu, Lucia
AU  - Radmilović Milena
AU  - Riemer, Cathy
AU  - Satta, Stefania
AU  - Schrijver, Iris
AU  - Stojiljković, Maja
AU  - Thein, Swee Lay
AU  - Traeger-Synodinos, Jan
AU  - Tully, Ray
AU  - Wada, Takahito
AU  - Waye, John S.
AU  - Wiemann, Claudia
AU  - Zukić, Branka
AU  - Chui, David H. K.
AU  - Wajcman, Henri
AU  - Hardison, Ross C.
AU  - Patrinos, George P.
PY  - 2011
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/539
AB  - We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories. A total of 1,941 unique genetic variants in 37 genes, encoding globins and other erythroid proteins, are currently documented in these databases, with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants, leading to a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The principles established here will serve as a model for other systems and for the analysis of other common and/or complex human genetic diseases.
PB  - Nature Publishing Group, New York
T2  - Nature Genetics
T1  - Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach
EP  - 302
IS  - 4
SP  - 295
VL  - 43
DO  - 10.1038/ng.785
ER  - 

@article{
author = "Giardine, Belinda and Borg, Joseph and Higgs, Douglas R. and Peterson, Kenneth R. and Philipsen, Sjaak and Maglott, Donna and Singleton, Belinda K. and Anstee, David J. and Basak, A. Nazli and Clark, Barnaby and Costa, Flavia C. and Faustino, Paula and Fedosyuk, Halyna and Felice, Alex E. and Francina, Alain and Galanello, Renzo and Gallivan, Monica V. E. and Georgitsi, Marianthi and Gibbons, Richard J. and Giordano, Piero C. and Harteveld, Cornelis L. and Hoyer, James D. and Jarvis, Martin and Joly, Philippe and Kanavakis, Emmanuel and Kollia, Panagoula and Menzel, Stephan and Miller, Webb and Moradkhani, Kamran and Old, John and Papachatzopoulou, Adamantia and Papadakis, Manoussos N. and Papadopoulos, Petros and Pavlović, Sonja and Perseu, Lucia and Radmilović Milena and Riemer, Cathy and Satta, Stefania and Schrijver, Iris and Stojiljković, Maja and Thein, Swee Lay and Traeger-Synodinos, Jan and Tully, Ray and Wada, Takahito and Waye, John S. and Wiemann, Claudia and Zukić, Branka and Chui, David H. K. and Wajcman, Henri and Hardison, Ross C. and Patrinos, George P.",
year = "2011",
abstract = "We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories. A total of 1,941 unique genetic variants in 37 genes, encoding globins and other erythroid proteins, are currently documented in these databases, with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants, leading to a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The principles established here will serve as a model for other systems and for the analysis of other common and/or complex human genetic diseases.",
publisher = "Nature Publishing Group, New York",
journal = "Nature Genetics",
title = "Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach",
pages = "302-295",
number = "4",
volume = "43",
doi = "10.1038/ng.785"
}

Giardine, B., Borg, J., Higgs, D. R., Peterson, K. R., Philipsen, S., Maglott, D., Singleton, B. K., Anstee, D. J., Basak, A. N., Clark, B., Costa, F. C., Faustino, P., Fedosyuk, H., Felice, A. E., Francina, A., Galanello, R., Gallivan, M. V. E., Georgitsi, M., Gibbons, R. J., Giordano, P. C., Harteveld, C. L., Hoyer, J. D., Jarvis, M., Joly, P., Kanavakis, E., Kollia, P., Menzel, S., Miller, W., Moradkhani, K., Old, J., Papachatzopoulou, A., Papadakis, M. N., Papadopoulos, P., Pavlović, S., Perseu, L., Radmilović Milena, Riemer, C., Satta, S., Schrijver, I., Stojiljković, M., Thein, S. L., Traeger-Synodinos, J., Tully, R., Wada, T., Waye, J. S., Wiemann, C., Zukić, B., Chui, D. H. K., Wajcman, H., Hardison, R. C.,& Patrinos, G. P.. (2011). Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach. in Nature Genetics
Nature Publishing Group, New York., 43(4), 295-302.
https://doi.org/10.1038/ng.785

Giardine B, Borg J, Higgs DR, Peterson KR, Philipsen S, Maglott D, Singleton BK, Anstee DJ, Basak AN, Clark B, Costa FC, Faustino P, Fedosyuk H, Felice AE, Francina A, Galanello R, Gallivan MVE, Georgitsi M, Gibbons RJ, Giordano PC, Harteveld CL, Hoyer JD, Jarvis M, Joly P, Kanavakis E, Kollia P, Menzel S, Miller W, Moradkhani K, Old J, Papachatzopoulou A, Papadakis MN, Papadopoulos P, Pavlović S, Perseu L, Radmilović Milena, Riemer C, Satta S, Schrijver I, Stojiljković M, Thein SL, Traeger-Synodinos J, Tully R, Wada T, Waye JS, Wiemann C, Zukić B, Chui DHK, Wajcman H, Hardison RC, Patrinos GP. Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach. in Nature Genetics. 2011;43(4):295-302.
doi:10.1038/ng.785 .

Giardine, Belinda, Borg, Joseph, Higgs, Douglas R., Peterson, Kenneth R., Philipsen, Sjaak, Maglott, Donna, Singleton, Belinda K., Anstee, David J., Basak, A. Nazli, Clark, Barnaby, Costa, Flavia C., Faustino, Paula, Fedosyuk, Halyna, Felice, Alex E., Francina, Alain, Galanello, Renzo, Gallivan, Monica V. E., Georgitsi, Marianthi, Gibbons, Richard J., Giordano, Piero C., Harteveld, Cornelis L., Hoyer, James D., Jarvis, Martin, Joly, Philippe, Kanavakis, Emmanuel, Kollia, Panagoula, Menzel, Stephan, Miller, Webb, Moradkhani, Kamran, Old, John, Papachatzopoulou, Adamantia, Papadakis, Manoussos N., Papadopoulos, Petros, Pavlović, Sonja, Perseu, Lucia, Radmilović Milena, Riemer, Cathy, Satta, Stefania, Schrijver, Iris, Stojiljković, Maja, Thein, Swee Lay, Traeger-Synodinos, Jan, Tully, Ray, Wada, Takahito, Waye, John S., Wiemann, Claudia, Zukić, Branka, Chui, David H. K., Wajcman, Henri, Hardison, Ross C., Patrinos, George P., "Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach" in Nature Genetics, 43, no. 4 (2011):295-302,
https://doi.org/10.1038/ng.785 . .