Identification and Classification of Novel Genetic Variants: En Route to the Diagnosis of Primary Ciliary Dyskinesia
Аутори
Stevanović, NinaSkakić, Anita
Minić, Predrag
Sovtić, Aleksandar
Stojiljković, Maja
Pavlović, Sonja
Anđelković, Marina
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Primary ciliary dyskinesia (PCD) is a disease caused by impaired function of motile cilia. PCD mainly affects the lungs and reproductive organs. Inheritance is autosomal recessive and X-linked. PCD patients have diverse clinical manifestations, thus making the establishment of proper diagnosis challenging. The utility of next-generation sequencing (NGS) technology for diagnostic purposes allows for better understanding of the PCD genetic background. However, identification of specific disease-causing variants is difficult. The main aim of this study was to create a unique guideline that will enable the standardization of the assessment of novel genetic variants within PCD-associated genes. The designed pipeline consists of three main steps: (1) sequencing, detection, and identification of genes/variants; (2) classification of variants according to their effect; and (3) variant characterization using in silico structural and functional analysis. The pipeline was validated through the an...alysis of the variants detected in a well-known PCD disease-causing gene (DNAI1) and the novel candidate gene (SPAG16). The application of this pipeline resulted in identification of potential disease-causing variants, as well as validation of the variants pathogenicity, through their analysis on transcriptional, translational, and posttranslational levels. The application of this pipeline leads to the confirmation of PCD diagnosis and enables a shift from candidate to PCD disease-causing gene.
Кључне речи:
SPAG16 / PCD / NGS / in silico structural analysis / functional analysis / DNAI1Извор:
International Journal of Molecular Sciences, 2021, 22, 16Издавач:
- MDPI, Basel
Финансирање / пројекти:
- Ministry of 332 Education, Science and Technological Development, Republic of Serbia [III 41004]
DOI: 10.3390/ijms22168821
ISSN: 1422-0067
PubMed: 34445527
WoS: 000689080400001
Scopus: 2-s2.0-85112539602
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Stevanović, Nina AU - Skakić, Anita AU - Minić, Predrag AU - Sovtić, Aleksandar AU - Stojiljković, Maja AU - Pavlović, Sonja AU - Anđelković, Marina PY - 2021 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1456 AB - Primary ciliary dyskinesia (PCD) is a disease caused by impaired function of motile cilia. PCD mainly affects the lungs and reproductive organs. Inheritance is autosomal recessive and X-linked. PCD patients have diverse clinical manifestations, thus making the establishment of proper diagnosis challenging. The utility of next-generation sequencing (NGS) technology for diagnostic purposes allows for better understanding of the PCD genetic background. However, identification of specific disease-causing variants is difficult. The main aim of this study was to create a unique guideline that will enable the standardization of the assessment of novel genetic variants within PCD-associated genes. The designed pipeline consists of three main steps: (1) sequencing, detection, and identification of genes/variants; (2) classification of variants according to their effect; and (3) variant characterization using in silico structural and functional analysis. The pipeline was validated through the analysis of the variants detected in a well-known PCD disease-causing gene (DNAI1) and the novel candidate gene (SPAG16). The application of this pipeline resulted in identification of potential disease-causing variants, as well as validation of the variants pathogenicity, through their analysis on transcriptional, translational, and posttranslational levels. The application of this pipeline leads to the confirmation of PCD diagnosis and enables a shift from candidate to PCD disease-causing gene. PB - MDPI, Basel T2 - International Journal of Molecular Sciences T1 - Identification and Classification of Novel Genetic Variants: En Route to the Diagnosis of Primary Ciliary Dyskinesia IS - 16 VL - 22 DO - 10.3390/ijms22168821 ER -
@article{ author = "Stevanović, Nina and Skakić, Anita and Minić, Predrag and Sovtić, Aleksandar and Stojiljković, Maja and Pavlović, Sonja and Anđelković, Marina", year = "2021", abstract = "Primary ciliary dyskinesia (PCD) is a disease caused by impaired function of motile cilia. PCD mainly affects the lungs and reproductive organs. Inheritance is autosomal recessive and X-linked. PCD patients have diverse clinical manifestations, thus making the establishment of proper diagnosis challenging. The utility of next-generation sequencing (NGS) technology for diagnostic purposes allows for better understanding of the PCD genetic background. However, identification of specific disease-causing variants is difficult. The main aim of this study was to create a unique guideline that will enable the standardization of the assessment of novel genetic variants within PCD-associated genes. The designed pipeline consists of three main steps: (1) sequencing, detection, and identification of genes/variants; (2) classification of variants according to their effect; and (3) variant characterization using in silico structural and functional analysis. The pipeline was validated through the analysis of the variants detected in a well-known PCD disease-causing gene (DNAI1) and the novel candidate gene (SPAG16). The application of this pipeline resulted in identification of potential disease-causing variants, as well as validation of the variants pathogenicity, through their analysis on transcriptional, translational, and posttranslational levels. The application of this pipeline leads to the confirmation of PCD diagnosis and enables a shift from candidate to PCD disease-causing gene.", publisher = "MDPI, Basel", journal = "International Journal of Molecular Sciences", title = "Identification and Classification of Novel Genetic Variants: En Route to the Diagnosis of Primary Ciliary Dyskinesia", number = "16", volume = "22", doi = "10.3390/ijms22168821" }
Stevanović, N., Skakić, A., Minić, P., Sovtić, A., Stojiljković, M., Pavlović, S.,& Anđelković, M.. (2021). Identification and Classification of Novel Genetic Variants: En Route to the Diagnosis of Primary Ciliary Dyskinesia. in International Journal of Molecular Sciences MDPI, Basel., 22(16). https://doi.org/10.3390/ijms22168821
Stevanović N, Skakić A, Minić P, Sovtić A, Stojiljković M, Pavlović S, Anđelković M. Identification and Classification of Novel Genetic Variants: En Route to the Diagnosis of Primary Ciliary Dyskinesia. in International Journal of Molecular Sciences. 2021;22(16). doi:10.3390/ijms22168821 .
Stevanović, Nina, Skakić, Anita, Minić, Predrag, Sovtić, Aleksandar, Stojiljković, Maja, Pavlović, Sonja, Anđelković, Marina, "Identification and Classification of Novel Genetic Variants: En Route to the Diagnosis of Primary Ciliary Dyskinesia" in International Journal of Molecular Sciences, 22, no. 16 (2021), https://doi.org/10.3390/ijms22168821 . .