UNIT 6.12 Discovery of Rare Homozygous Mutations from Studies of Consanguineous Pedigrees

  1. Fowzan S. Alkuraya1,2,3

Published Online: 1 OCT 2012

DOI: 10.1002/0471142905.hg0612s75

Current Protocols in Human Genetics

Current Protocols in Human Genetics

How to Cite

Alkuraya, F. S. 2012. Discovery of Rare Homozygous Mutations from Studies of Consanguineous Pedigrees. Current Protocols in Human Genetics. 75:6.12:6.12.1–6.12.13.

Author Information

  1. 1

    Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

  2. 2

    Department of Pediatrics, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh, Saudi Arabia

  3. 3

    Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

Publication History

  1. Published Online: 1 OCT 2012


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.


  • autozygome;
  • autozygosity;
  • homozygosity;
  • mapping;
  • linkage;
  • exome