Are moment bounds on the recombination fraction between a marker and a disease
locus too good to be true? Allelic association mapping revisited for simple genetic diseases
in the Finnish population
N.L. Kaplan, B.S. Weir
American Journal of Human Genetics ,
57(6), 1486-1498 (Dec 1995)
Abstract
In the past several years, allelic association has helped map a number of rare
genetic diseases in the human genome. A commonly used upper bound on the
recombination fraction between the disease gene and an associated marker is known to be
biased downward, so there is the possibility that an investigator could be misled. This
upper bound is based on a moment equation that can be derived within the context of a
Poisson branching process, so its performance can be compared with a recently proposed
likelihood bound. We show that the confidence level of the moment upper bound is much
lower than expected, while the confidence level of the likelihood bound is in line with
expectation. The effects of mutation at either the marker or disease locus on the upper
bounds are also investigated. Results indicate that mutation is not an important force for
typical mutation rates, unless the recombination fraction between the marker and disease
locus is very small or the disease allele is very rare in the general population. Finally, the
impact of sample size on the likelihood bound is investigated. The results are illustrated
with data on 10 simple genetic diseased in the Finnish population.
Association Studies