Unique pipeline for the assessment of novel genetic variants leads to confirmation of PCD diagnosis
Аутори
Stevanović, NinaAnđelković, Marina
Skakić, Anita
Spasovski, Vesna
Stojiljković, Maja
Parezanović, Marina
Ugrin, Milena
Pavlović, Sonja
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Background/Objectives: Primary ciliary dyskinesia (PCD) is a
disease caused by impaired ciliary motility and mainly affects the
lungs and reproductive organs. Inheritance is autosomal recessive
and X-linked with more than 40 disease-causing genes, wherefore
PCD patients have diverse clinical manifestations, thus making
diagnosis difficult. The utility of next-generation sequencing (NGS)
technology for diagnostic purposes allows a better understanding
of the PCD genetic background. However, the identification of
specific disease-causing variants is challenging. The objective of
this study was to create a unique guideline that will enable the
standardization of the assessment of novel variants within PCD
associated genes.
Methods: The study included designing a pipeline for the classification
of the rare genetic variants detected using NGS. The pipeline
included in silico (translation, 3D-model, protein-protein interactions,
sequence conservation, posttranslational modific...ations) and functional
analysis (expressional analysis, Western Blot) of the variants.
Results: The designed pipeline consists of three steps: sequencing,
detection, and identification of genes/variants; classification of
variants according to their effect; and variant characterization using
in silico structural and functional analysis. The pipeline was validated
by the analysis of the variants detected in a disease-causing
gene (DNAI1) and the novel candidate gene (SPAG16).
Conclusion: The application of the pipeline resulted in the
identification of disease-causing variants, as well as pathogenicity
validation, through the analysis on transcriptional, translational,
and posttranslational levels.The application of created pipeline
leads to the confirmation of PCD diagnosis and enables a shift
from candidate to disease-causing gene.
Извор:
European Journal of Human Genetic, 2023, 31, Supplement S1, 383-383Издавач:
- Springer Nature
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200042 (Универзитет у Београду, Институт за молекуларну генетику и генетичко инжењерство) (RS-MESTD-inst-2020-200042)
Напомена:
- Abstracts from the 55th European Society of Human Genetics (ESHG) Conference
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Stevanović, Nina AU - Anđelković, Marina AU - Skakić, Anita AU - Spasovski, Vesna AU - Stojiljković, Maja AU - Parezanović, Marina AU - Ugrin, Milena AU - Pavlović, Sonja PY - 2023 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2275 AB - Background/Objectives: Primary ciliary dyskinesia (PCD) is a disease caused by impaired ciliary motility and mainly affects the lungs and reproductive organs. Inheritance is autosomal recessive and X-linked with more than 40 disease-causing genes, wherefore PCD patients have diverse clinical manifestations, thus making diagnosis difficult. The utility of next-generation sequencing (NGS) technology for diagnostic purposes allows a better understanding of the PCD genetic background. However, the identification of specific disease-causing variants is challenging. The objective of this study was to create a unique guideline that will enable the standardization of the assessment of novel variants within PCD associated genes. Methods: The study included designing a pipeline for the classification of the rare genetic variants detected using NGS. The pipeline included in silico (translation, 3D-model, protein-protein interactions, sequence conservation, posttranslational modifications) and functional analysis (expressional analysis, Western Blot) of the variants. Results: The designed pipeline consists of three steps: sequencing, detection, and identification of genes/variants; classification of variants according to their effect; and variant characterization using in silico structural and functional analysis. The pipeline was validated by the analysis of the variants detected in a disease-causing gene (DNAI1) and the novel candidate gene (SPAG16). Conclusion: The application of the pipeline resulted in the identification of disease-causing variants, as well as pathogenicity validation, through the analysis on transcriptional, translational, and posttranslational levels.The application of created pipeline leads to the confirmation of PCD diagnosis and enables a shift from candidate to disease-causing gene. PB - Springer Nature C3 - European Journal of Human Genetic T1 - Unique pipeline for the assessment of novel genetic variants leads to confirmation of PCD diagnosis EP - 383 IS - Supplement S1 SP - 383 VL - 31 DO - 10.1038/s41431-023-01338-4 ER -
@conference{ author = "Stevanović, Nina and Anđelković, Marina and Skakić, Anita and Spasovski, Vesna and Stojiljković, Maja and Parezanović, Marina and Ugrin, Milena and Pavlović, Sonja", year = "2023", abstract = "Background/Objectives: Primary ciliary dyskinesia (PCD) is a disease caused by impaired ciliary motility and mainly affects the lungs and reproductive organs. Inheritance is autosomal recessive and X-linked with more than 40 disease-causing genes, wherefore PCD patients have diverse clinical manifestations, thus making diagnosis difficult. The utility of next-generation sequencing (NGS) technology for diagnostic purposes allows a better understanding of the PCD genetic background. However, the identification of specific disease-causing variants is challenging. The objective of this study was to create a unique guideline that will enable the standardization of the assessment of novel variants within PCD associated genes. Methods: The study included designing a pipeline for the classification of the rare genetic variants detected using NGS. The pipeline included in silico (translation, 3D-model, protein-protein interactions, sequence conservation, posttranslational modifications) and functional analysis (expressional analysis, Western Blot) of the variants. Results: The designed pipeline consists of three steps: sequencing, detection, and identification of genes/variants; classification of variants according to their effect; and variant characterization using in silico structural and functional analysis. The pipeline was validated by the analysis of the variants detected in a disease-causing gene (DNAI1) and the novel candidate gene (SPAG16). Conclusion: The application of the pipeline resulted in the identification of disease-causing variants, as well as pathogenicity validation, through the analysis on transcriptional, translational, and posttranslational levels.The application of created pipeline leads to the confirmation of PCD diagnosis and enables a shift from candidate to disease-causing gene.", publisher = "Springer Nature", journal = "European Journal of Human Genetic", title = "Unique pipeline for the assessment of novel genetic variants leads to confirmation of PCD diagnosis", pages = "383-383", number = "Supplement S1", volume = "31", doi = "10.1038/s41431-023-01338-4" }
Stevanović, N., Anđelković, M., Skakić, A., Spasovski, V., Stojiljković, M., Parezanović, M., Ugrin, M.,& Pavlović, S.. (2023). Unique pipeline for the assessment of novel genetic variants leads to confirmation of PCD diagnosis. in European Journal of Human Genetic Springer Nature., 31(Supplement S1), 383-383. https://doi.org/10.1038/s41431-023-01338-4
Stevanović N, Anđelković M, Skakić A, Spasovski V, Stojiljković M, Parezanović M, Ugrin M, Pavlović S. Unique pipeline for the assessment of novel genetic variants leads to confirmation of PCD diagnosis. in European Journal of Human Genetic. 2023;31(Supplement S1):383-383. doi:10.1038/s41431-023-01338-4 .
Stevanović, Nina, Anđelković, Marina, Skakić, Anita, Spasovski, Vesna, Stojiljković, Maja, Parezanović, Marina, Ugrin, Milena, Pavlović, Sonja, "Unique pipeline for the assessment of novel genetic variants leads to confirmation of PCD diagnosis" in European Journal of Human Genetic, 31, no. Supplement S1 (2023):383-383, https://doi.org/10.1038/s41431-023-01338-4 . .