Multipoint Analysis of Human Quantitative Genetic Variation
Goldgar DE
Department of Medical Informatics, University of Utah, Salt Lake City
84108.
American Journal of Human Genetics, 47(6):957-967 (Dec 1990)
Abstract
A unique method of partitioning human quantitative genetic variation into
effects due to specific chromosomal regions is presented. This method is
based on estimating the proportion of genetic material, R, shared identical by
descent (IBD) by sibling pairs in a specified chromosomal region, on the
basis of their marker genotypes at a set of marker loci spanning the region.
The mean and variance of the distribution of R conditional on IBD status
and recombination pattern between two marker loci are derived as a function
of the distance between the two loci. The distribution of the estimates of R is
exemplified using data on 22 loci on chromosome 7. A method of using the
estimated R values and observed values of a quantitative trait in a set of
sibships to estimate the proportion of total genetic variance explained by loci
in the region of interest is presented. Monte Carlo simulation techniques are
used to show that this method is more powerful than existing methods of
quantitative linkage analysis based on sib pairs. It is also shown through
simulation studies that the proposed method is sensitive to genetic variation
arising from both a single locus of large effect as well as from several loosely
linked loci of moderate phenotypic effect.
Variance component linkage analysis