CATCHing putative causative variants in consanguineous families

BMC Bioinformatics

Software

Periklis Makrythanasis¹  Federico Andrea Santoni¹  Stylianos E. Antonarakis² 

[1] Department of Genetic Medicine and Development, University of Geneva, Rue Michel Servet 1, Geneva, Switzerland;University Hospitals of Geneva - HUG, Rue Gabrielle-Perret Gentil 4, Geneva, Switzerland;Department of Genetic Medicine and Development, University of Geneva, Rue Michel Servet 1, Geneva, Switzerland;University Hospitals of Geneva - HUG, Rue Gabrielle-Perret Gentil 4, Geneva, Switzerland;IGE3 Institute of Genetics and Genomics of Geneva, Geneva, Switzerland;

关键词: Causative Variant;    Pathogenic Variant;    Whole Exome Sequencing;    Autosomal Recessive;    Consanguineous Family;   

DOI  :  10.1186/s12859-015-0727-5

 received in 2015-03-16, accepted in 2015-09-06,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundConsanguinity 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.ResultsTo 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.ConclusionsCATCH 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.

【 授权许可】

CC BY   
© Santoni et al. 2015