Genomic Patterns of Homozygosity in Worldwide Human Populations

Department of Biology, Stanford University, Stanford, CA 94305, USA.
The American Journal of Human Genetics (Impact Factor: 10.93). 08/2012; 91(2):275-92. DOI: 10.1016/j.ajhg.2012.06.014
Source: PubMed


Genome-wide patterns of homozygosity runs and their variation across individuals provide a valuable and often untapped resource for studying human genetic diversity and evolutionary history. Using genotype data at 577,489 autosomal SNPs, we employed a likelihood-based approach to identify runs of homozygosity (ROH) in 1,839 individuals representing 64 worldwide populations, classifying them by length into three classes-short, intermediate, and long-with a model-based clustering algorithm. For each class, the number and total length of ROH per individual show considerable variation across individuals and populations. The total lengths of short and intermediate ROH per individual increase with the distance of a population from East Africa, in agreement with similar patterns previously observed for locus-wise homozygosity and linkage disequilibrium. By contrast, total lengths of long ROH show large interindividual variations that probably reflect recent inbreeding patterns, with higher values occurring more often in populations with known high frequencies of consanguineous unions. Across the genome, distributions of ROH are not uniform, and they have distinctive continental patterns. ROH frequencies across the genome are correlated with local genomic variables such as recombination rate, as well as with signals of recent positive selection. In addition, long ROH are more frequent in genomic regions harboring genes associated with autosomal-dominant diseases than in regions not implicated in Mendelian diseases. These results provide insight into the way in which homozygosity patterns are produced, and they generate baseline homozygosity patterns that can be used to aid homozygosity mapping of genes associated with recessive diseases.

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Available from: Marcus W Feldman, Mar 18, 2014
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    • "(R Core Team, 2012). To assess population-specific differences in the spatial distribution of ROHs across the genome, 'ROH hotspots' were identified as locations of the genome for which the proportion of individuals showing a ROH (f ROH ) exceeded the 99th percentile of the distribution of f ROH in the population (Pemberton et al., 2012). In so doing, we grouped individuals into the four previously used populations (that is, WSar, WIta, WEur and DP). "
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    • "Runs of homozygosity (ROHs) were detected by a sliding window algorithm with a window size of 100 SNPs [14] [15]. ROHs longer than 1 Mb were used to assist in filtering the variants identified by exome sequencing, since runs of this length are uncommon in the general population [16]. Variant alleles with a minor allele frequency (MAF) of less than 1% in the 1000 Genomes Project ( "
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