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Exome-Sequence Analyses of Four Multi-Incident Multiple Sclerosis Families

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the Central Nervous System (CNS). Currently, it is estimated that 30–40% of the phenotypic variability of MS can be explained by genetic factors. However, low susceptibility variants identified through Genome Wide Association Study...

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Autores principales: Zrzavy, Tobias, Leutmezer, Fritz, Kristoferitsch, Wolfgang, Kornek, Barbara, Schneider, Christine, Rommer, Paulus, Berger, Thomas, Zimprich, Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563748/
https://www.ncbi.nlm.nih.gov/pubmed/32854198
http://dx.doi.org/10.3390/genes11090988
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author Zrzavy, Tobias
Leutmezer, Fritz
Kristoferitsch, Wolfgang
Kornek, Barbara
Schneider, Christine
Rommer, Paulus
Berger, Thomas
Zimprich, Alexander
author_facet Zrzavy, Tobias
Leutmezer, Fritz
Kristoferitsch, Wolfgang
Kornek, Barbara
Schneider, Christine
Rommer, Paulus
Berger, Thomas
Zimprich, Alexander
author_sort Zrzavy, Tobias
collection PubMed
description Multiple sclerosis (MS) is an inflammatory demyelinating disease of the Central Nervous System (CNS). Currently, it is estimated that 30–40% of the phenotypic variability of MS can be explained by genetic factors. However, low susceptibility variants identified through Genome Wide Association Study (GWAS) were calculated to explain about 50% of the heritability. Whether familial high-risk variants also contribute to heritability is a subject of controversy. In the last few years, several familial variants have been nominated, but none of them have been unequivocally confirmed. One reason for this may be that genetic heterogeneity and reduced penetrance are hindering detection. Sequencing a large number of MS families is needed to answer this question. In this study, we performed whole exome sequencing in four multi-case families, of which at least three affected individuals per family were analyzed. We identified a total of 138 rare variants segregating with disease in each of the families. Although no single variant showed convincing evidence for disease causation, some genes seemed particularly interesting based on their biological function. The main aim of this study was to provide a complete list of all rare segregating variants to provide the possibility for other researchers to cross-check familial candidate genes in an unbiased manner.
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spelling pubmed-75637482020-10-27 Exome-Sequence Analyses of Four Multi-Incident Multiple Sclerosis Families Zrzavy, Tobias Leutmezer, Fritz Kristoferitsch, Wolfgang Kornek, Barbara Schneider, Christine Rommer, Paulus Berger, Thomas Zimprich, Alexander Genes (Basel) Brief Report Multiple sclerosis (MS) is an inflammatory demyelinating disease of the Central Nervous System (CNS). Currently, it is estimated that 30–40% of the phenotypic variability of MS can be explained by genetic factors. However, low susceptibility variants identified through Genome Wide Association Study (GWAS) were calculated to explain about 50% of the heritability. Whether familial high-risk variants also contribute to heritability is a subject of controversy. In the last few years, several familial variants have been nominated, but none of them have been unequivocally confirmed. One reason for this may be that genetic heterogeneity and reduced penetrance are hindering detection. Sequencing a large number of MS families is needed to answer this question. In this study, we performed whole exome sequencing in four multi-case families, of which at least three affected individuals per family were analyzed. We identified a total of 138 rare variants segregating with disease in each of the families. Although no single variant showed convincing evidence for disease causation, some genes seemed particularly interesting based on their biological function. The main aim of this study was to provide a complete list of all rare segregating variants to provide the possibility for other researchers to cross-check familial candidate genes in an unbiased manner. MDPI 2020-08-25 /pmc/articles/PMC7563748/ /pubmed/32854198 http://dx.doi.org/10.3390/genes11090988 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Zrzavy, Tobias
Leutmezer, Fritz
Kristoferitsch, Wolfgang
Kornek, Barbara
Schneider, Christine
Rommer, Paulus
Berger, Thomas
Zimprich, Alexander
Exome-Sequence Analyses of Four Multi-Incident Multiple Sclerosis Families
title Exome-Sequence Analyses of Four Multi-Incident Multiple Sclerosis Families
title_full Exome-Sequence Analyses of Four Multi-Incident Multiple Sclerosis Families
title_fullStr Exome-Sequence Analyses of Four Multi-Incident Multiple Sclerosis Families
title_full_unstemmed Exome-Sequence Analyses of Four Multi-Incident Multiple Sclerosis Families
title_short Exome-Sequence Analyses of Four Multi-Incident Multiple Sclerosis Families
title_sort exome-sequence analyses of four multi-incident multiple sclerosis families
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563748/
https://www.ncbi.nlm.nih.gov/pubmed/32854198
http://dx.doi.org/10.3390/genes11090988
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