CATCHing putative causative variants in consanguineous families.

Details

Serval ID
serval:BIB_9779B593FB30
Type
Article: article from journal or magazin.
Collection
Publications
Title
CATCHing putative causative variants in consanguineous families.
Journal
BMC bioinformatics
Author(s)
Santoni F.A., Makrythanasis P., Antonarakis S.E.
ISSN
1471-2105 (Electronic)
ISSN-L
1471-2105
Publication state
Published
Issued date
28/09/2015
Peer-reviewed
Oui
Volume
16
Pages
310
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Consanguinity is an important risk factor for autosomal recessive (AR) disorders. Extended genomic regions identical by descent (IBD) in the offspring of consanguineous parents give rise to recessive disorders with identical (homozygous) pathogenic variants in both alleles. However, many clinical phenotypes presenting in the offspring of consanguineous couples are still of unknown etiology. Nowadays advances in High Throughput Sequencing provide an excellent opportunity to achieve a molecular diagnosis or to identify novel candidate genes.
To exploit all available information from the family structure we developed CATCH, an algorithm that combines genotyped SNPs of all family members for the optimal detection of Runs Of Homozygosity (ROH) and exome sequencing data from one affected individual to identify putative causative variants in consanguineous families.
CATCH proved to be effective in discovering known or putative new causative variants in 43 out of 50 consanguineous families. Among them, novel variants causative of familial thrombocytopenia, sclerosis bone dysplasia and the first homozygous loss-of-function mutation in FGFR3 in human causing severe skeletal deformities, tall stature and hearing impairment were identified.
Keywords
Algorithms, Consanguinity, Genotype, High-Throughput Nucleotide Sequencing, Homozygote, Humans, Internet, Musculoskeletal Diseases/genetics, Musculoskeletal Diseases/pathology, Pedigree, Phenotype, Polymorphism, Single Nucleotide, Receptor, Fibroblast Growth Factor, Type 3/genetics, Sequence Analysis, DNA, User-Computer Interface
Pubmed
Web of science
Open Access
Yes
Create date
20/05/2019 13:40
Last modification date
07/04/2025 15:53
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