Estimation of Recent and Ancient Inbreeding in a Small Endogamous Tunisian Community Through Genomic Runs of Homozygosity

Ann Hum Genet. 2015 Nov;79(6):402-17. doi: 10.1111/ahg.12131. Epub 2015 Sep 29.

Abstract

Runs of homozygosity (ROHs) are extended genomic regions of homozygous genotypes that record populations' mating patterns in the past. We performed microarray genotyping on 15 individuals from a small isolated Tunisian community. We estimated the individual and population genome-wide level of homozygosity from data on ROH above 0.5 Mb in length. We found a high average number of ROH per individual (48.2). The smallest ROH category (0.5-1.49 Mb) represents 0.93% of the whole genome, while medium-size (1.5-4.99 Mb) and long-size ROH (≥5 Mb) cover 1.18% and 0.95%, respectively. We found that genealogical individual inbreeding coefficients (Fped ) based on three- to four-generation pedigrees are not reliable indicators of the current proportion of genome-wide homozygosity inferred from ROH (FROH ) either for 0.5 or 1.5 Mb ROH length thresholds, while identity-by-descent sharing is a function of shared coancestry. This study emphasizes the effect of reproductive isolation and a prolonged practice of consanguinity that limits the genetic heterogeneity. It also provides evidence of both recent and ancient parental relatedness contribution to the current level of genome-wide homozygosity in the studied population. These findings may be useful for evaluation of long-term effects of inbreeding on human health and for future applications of ROHs in identifying recessive susceptibility genes.

Keywords: Tunisia; genealogy; human isolate; identity-by-descent; inbreeding; run of homozygosity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Consanguinity*
  • Female
  • Genome, Human*
  • Genotype
  • Homozygote*
  • Humans
  • Male
  • Pedigree
  • Reproductive Isolation
  • Sequence Analysis, DNA*
  • Tunisia