| Autor: |
Swinford NA; Department of Anthropology, University of California Davis, Davis, CA 95616., Prall SP; Department of Anthropology, University of Missouri, Columbia, MO 65211., Gopalan S; Department of Evolutionary Anthropology, Duke University, Durham, NC 27708., Williams CM; Center for Computational Molecular Biology, Brown University, Providence, RI 02912., Sheehama J; Department of Human, Biological and Translational Medical Sciences, School of Medicine University of Namibia, Oshakati 10005, Namibia., Scelza BA; Department of Anthropology, University of California Los Angeles, Los Angeles, CA 90095., Henn BM; Department of Anthropology, University of California Davis, Davis, CA 95616.; Center for Population Biology, University of California Davis, Davis, CA 95616.; Genome Center, University of California Davis, Davis, CA 95616. |
| Abstrakt: |
Recessive alleles have been shown to directly affect both human Mendelian disease phenotypes and complex traits. Pedigree studies also suggest that consanguinity results in increased childhood mortality and adverse health phenotypes, presumably through penetrance of recessive mutations. Here, we test whether the accumulation of homozygous, recessive alleles decreases reproductive success in a human population. We address this question among the Namibian Himba, an endogamous agro-pastoralist population, who until very recently practiced natural fertility. Using a sample of 681 individuals, we show that Himba exhibit elevated levels of "inbreeding," calculated as the fraction of the genome in runs of homozygosity (F ROH ). Many individuals contain multiple long segments of ROH in their genomes, indicating that their parents had high kinship coefficients. However, we do not find evidence that this is explained by first-cousin consanguinity, despite a reported social preference for cross-cousin marriages. Rather, we show that elevated haplotype sharing in the Himba is due to a bottleneck, likely in the past 60 generations. We test whether increased recessive mutation load results in observed fitness consequences by assessing the effect of F ROH on completed fertility in a cohort of postreproductive women (n = 69). We find that higher F ROH is significantly associated with lower fertility. Our data suggest a multilocus genetic effect on fitness driven by the expression of deleterious recessive alleles, especially those in long ROH. However, these effects are not the result of consanguinity but rather elevated background identity by descent. |
