Deletions of recessive disease genes: CNV contribution to carrier states and disease-causing alleles

摘要: Over 1200 recessive disease genes have been described in humans. The prevalence, allelic architecture, and per-genome load of pathogenic alleles these remain to be fully elucidated, as does the contribution DNA copy-number variants (CNVs) carrier status disease. We mined CNV data from 21,470 individuals obtained by array-comparative genomic hybridization a clinical diagnostic setting identify deletions encompassing or disrupting genes. identified 3212 heterozygous potential affecting 419 unique Deletion frequency ranged one occurrence 1.5%. When compared with never deleted our cohort, affected at least deletion were longer located farther known dominant genes, suggesting that formation and/or prevalence CNVs may both local adjacent features selection. Some subjects had multiple (307 subjects) more than gene (206 deletions). Heterozygous spanning confer for single-gene disorders, complex syndromes resulting combination two conditions, potentially cause phenotypes due multiply state. In addition mutations, we homozygous hemizygous causative provide further evidence contribute architecture disease-causing mutations. Thus, complete screening method test should detect alleles.