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Discovery of Rare Homozygous Mutations from Studies of Consanguineous Pedigrees

2012; Wiley; Volume: 75; Issue: 1 Linguagem: Inglês

10.1002/0471142905.hg0612s75

1934-8266

Fowzan S. Alkuraya,

Genetics and Neurodevelopmental Disorders

Abstract The unmasking of recessive mutations by virtue of biparental inheritance of the same ancestral haplotype on which they reside (autozygosity) has provided human geneticists with one of their most powerful tools in unraveling the genetic basis of autosomal recessive disorders. This has historically been achieved by tracking the blocks of homozygosity as surrogates of autozygosity using polymorphic microsatellite markers. Mapping the entire set of autozygous blocks per individual (autozygome) at high resolution became possible with the advent of high‐density SNP arrays. The more recent availability of next‐generation sequencing has markedly accelerated the rate at which rare recessive mutations are identified by obviating the need to prioritize genes for sequencing within candidate autozygous loci. This unit will review the individual and combined use of these techniques in the context of mapping novel recessive disease genes, as well as potential pitfalls and recommended solutions. Curr. Protoc. Hum. Genet . 75:6.12.1‐6.12.13. © 2012 by John Wiley & Sons, Inc.