Genomic runs of homozygosity record population history and consanguinity - PubMed (original) (raw)

Genomic runs of homozygosity record population history and consanguinity

Mirna Kirin et al. PLoS One. 2010.

Abstract

The human genome is characterised by many runs of homozygous genotypes, where identical haplotypes were inherited from each parent. The length of each run is determined partly by the number of generations since the common ancestor: offspring of cousin marriages have long runs of homozygosity (ROH), while the numerous shorter tracts relate to shared ancestry tens and hundreds of generations ago. Human populations have experienced a wide range of demographic histories and hold diverse cultural attitudes to consanguinity. In a global population dataset, genome-wide analysis of long and shorter ROH allows categorisation of the mainly indigenous populations sampled here into four major groups in which the majority of the population are inferred to have: (a) recent parental relatedness (south and west Asians); (b) shared parental ancestry arising hundreds to thousands of years ago through long term isolation and restricted effective population size (N(e)), but little recent inbreeding (Oceanians); (c) both ancient and recent parental relatedness (Native Americans); and (d) only the background level of shared ancestry relating to continental N(e) (predominantly urban Europeans and East Asians; lowest of all in sub-Saharan African agriculturalists), and the occasional cryptically inbred individual. Moreover, individuals can be positioned along axes representing this demographic historic space. Long runs of homozygosity are therefore a globally widespread and under-appreciated characteristic of our genomes, which record past consanguinity and population isolation and provide a distinctive record of the demographic history of an individual's ancestors. Individual ROH measures will also allow quantification of the disease risk arising from polygenic recessive effects.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1

Figure 1. Global distribution of long runs of homozygosity.

The average total length of the genome in runs of homozygosity in a number of length categories is plotted for each continental region. The data for runs under 1 Mb (inset) are plotted on a different scale. For comparison, chromosome 1 is 224 Mb in length.

Figure 2

Figure 2. Runs of homozygosity in African hunter-gatherers and agriculturalist heritage populations.

The average total length of the genome in ROH in a number of length categories is plotted.

Figure 3

Figure 3. Individual patterns of long runs of homozygosity.

The number of runs of homozygosity compared to the total length in ROH for individuals from a number of illustrative populations. The Karitiana are from the Brazilian Amazon, the Mandenka from Senegal and the Baluchi from Pakistan. Cryptically inbred French, Japanese and Mandenka individuals plot to the right of the main population cluster in each case, as they carry longer ROH, but not that many more ROH. The length in ROH is very variable in the consanguineous Baluchi and Karitiana populations.

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References

    1. McQuillan R, Leutenegger AL, Abdel-Rahman R, Franklin CS, Pericic M, et al. Runs of homozygosity in European populations. Am J Hum Genet. 2008;83:359–372. - PMC - PubMed
    1. Woods CG, Cox J, Springell K, Hampshire DJ, Mohamed MD, et al. Quantification of homozygosity in consanguineous individuals with autosomal recessive disease. Am J Hum Genet. 2006;78:889–896. - PMC - PubMed
    1. Broman KW, Weber JL. Long homozygous chromosomal segments in reference families from the Centre d'Étude du Polymorphisme Humain. Am J Hum Genet. 1999;65:1493–1500. - PMC - PubMed
    1. Gibson J, Morton NE, Collins A. Extended tracts of homozygosity in outbred human populations. Hum Mol Genet. 2006;15:789–795. - PubMed
    1. Frazer KA, Ballinger DG, Cox DR, Hinds DA, Stuve LL, et al. A second generation human haplotype map of over 3.1 million SNPs. Nature. 2007;449:851–861. - PMC - PubMed

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