title: Estimating human inbreeding coefficients: comparison of genealogical and marker heterozygosity approaches.
abstract: 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.
authors.affiliation: MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK. a.carothers@hgu.mrc.ac.uk
authors.forename: A D
authors.initials: AD
authors.lastname: Carothers
authors.forename: I
authors.initials: I
authors.lastname: Rudan
authors.forename: I
authors.initials: I
authors.lastname: Kolcic
authors.forename: O
authors.initials: O
authors.lastname: Polasek
authors.forename: C
authors.initials: C
authors.lastname: Hayward
authors.forename: A F
authors.initials: AF
authors.lastname: Wright
authors.forename: H
authors.initials: H
authors.lastname: Campbell
authors.forename: P
authors.initials: P
authors.lastname: Teague
authors.forename: N D
authors.initials: ND
authors.lastname: Hastie
authors.forename: J L
authors.initials: JL
authors.lastname: Weber
mesh_terms: D003241:Consanguinity; D017523:Croatia; D005789:Genealogy and Heraldry; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012606:Scotland