Estimating Human Inbreeding Coefficients: Comparison of Genealogical and Marker Heterozygosity Approaches

• Published in: Annals of human genetics 2006-09, Vol.70 (5), p.666-676
• Main Authors: Carothers, A. D., Rudan, I., Kolcic, I., Polasek, O., Hayward, C., Wright, A. F., Campbell, H., Teague, P., Hastie, N. D., Weber, J. L.
• Format: Article
• Language: English
• Subjects: Consanguinity; Croatia; genealogy; Genealogy and Heraldry; Genotype; Heterozygote; Homozygote; human isolates; Humans; inbreeding; marker heterozygosity; Microsatellite Repeats - genetics; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Scotland
• ISSN: 0003-4800; 1469-1809
• DOI: 10.1111/j.1469-1809.2006.00263.x

Summary We have used genealogies and genomic polymorphisms to estimate individual inbreeding coefficients (F) in 50 subjects with an expected range (based on recent genealogies) of F from 0.0 to 0.0625. The estimates were based on two approaches, using genotypes respectively from 410 microsatellite markers (410‐STR panel) and from 10,000 SNPs (10K‐SNP panel). The latter was performed in a sub‐sample of 15 individuals. We concluded that for both marker panels measures of inbreeding based on the excess of homozygosity over Hardy‐Weinberg expectation were not closely correlated with 4‐5 generation genealogical F‐values. For the 10K‐SNP panel we found two alternative measures which correlated more closely with F, based respectively on standard errors and on paired homozygosity of nearby SNPs over distances of 2‐4 cM. We propose an empirical method for estimating standard errors and hence individual F‐values, based on the variation between individual autosomes. This method could provide useful estimates of average F‐values for groups of individuals in population‐based studies of the effects of inbreeding/homozygosity on quantitative traits.