CATCHing putative causative variants in consanguineous families. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Santoni, Federico; Makrythanasis, Periklis; Antonarakis, Stylianos
• Is Part Of: BMC bioinformatics. Volume 16:Issue 1(2015)
• Page Start: 1
• Page End: 5
• Publication Date: 2015-12
• Subjects: Bioinformatics -- Periodicals; Computational biology -- Periodicals; 570.285
• DOI: 10.1186/s12859-015-0727-5
• Languages: English
• ISSNs: 1471-2105

Abstract

Abstract Background Consanguinity is an important risk factor for autosomal recessive (AR) disorders. Extended genomic regionsidentical 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. Results 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. Conclusions 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 inFGFR3 in human causing severe skeletal deformities, tall stature and hearing impairment were identified.