Quantification of homozygosity in consanguineous individuals with autosomal recessive disease

Am J Hum Genet. 2006 May;78(5):889-896. doi: 10.1086/503875. Epub 2006 Mar 21.


Individuals born of consanguineous union have segments of their genomes that are homozygous as a result of inheriting identical ancestral genomic segments through both parents. One consequence of this is an increased incidence of recessive disease within these sibships. Theoretical calculations predict that 6% (1/16) of the genome of a child of first cousins will be homozygous and that the average homozygous segment will be 20 cM in size. We assessed whether these predictions held true in populations that have preferred consanguineous marriage for many generations. We found that in individuals with a recessive disease whose parents were first cousins, on average, 11% of their genomes were homozygous (n = 38; range 5%-20%), with each individual bearing 20 homozygous segments exceeding 3 cM (n = 38; range of number of homozygous segments 7-32), and that the size of the homozygous segment associated with recessive disease was 26 cM (n = 100; range 5-70 cM). These data imply that prolonged parental inbreeding has led to a background level of homozygosity increased approximately 5% over and above that predicted by simple models of consanguinity. This has important clinical and research implications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosome Disorders
  • Consanguinity*
  • Foot Deformities, Congenital
  • Genes, Recessive*
  • Genetic Diseases, Inborn
  • Genetic Linkage
  • Homozygote*
  • Humans
  • Lod Score
  • Male
  • Microsatellite Repeats
  • Pedigree
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide