Multipoint Mapping Under Genetic Interference
DE Weeks, GM Lathrop, J Ott
Human Heredity , 43(2),86--97 (1993 Mar-Apr)
Abstract
Genetic chiasma interference occurs when one crossover influences
the probability of another crossover occurring nearby. While
interference is known to occur in humans, it is typically ignored
when computing multipoint likelihoods for genetic mapping. This
biologically unsound assumption of no interference facilitates the
calculation of the likelihoods at the expense of reduced power to
accurately construct a genetic map. We have developed a computer
program that calculates multipoint likelihoods of three-generation
nuclear families while taking interference into account. In our
program, interference is modelled by using a map function to convert
genetic distances into recombination fractions. We can determine
which of several map functions best fits the data by comparing the
multipoint likelihoods of the data under each map function. Since
the distribution of the difference between likelihoods is unknown,
we use a simulation approach to determine the statistical
significance of our results. When our program is applied to six
loci, D10S34, D10S19, D10S16, D10S14, D10S4, and D10S20, from the
CEPH consortium map of chromosome 10, we find significant evidence
in favor of positive interference as modelled by the Sturt map
function.
