Linda Werner-Hartman

Gene mapping - what additional clues can haplotypes provide?

Abstract

Gene mapping aims at localizing the position of a disease carrying
gene.  In association studies the main idea is to examine if any of a
marker alleles from (appearently) unrelated individuals appears
together with a disease trait at a frequency significantly higher or
lower than random occurence. This could be caused either by direct
biological action of the polymorphism, or (more often) by the marker
allele being so close to the disease susceptibility allele that these
alleles will be inherited together over many generations.

Traditional methods in association analysis test departure from
independence for each marker independently. Lately, methods treating
all markers in a small area simultaneously, so called haplotype based
methods, have gained increased interest. The advantage of using
haplotypes are at least twofold. First: by studying several loci
simultaneously, the number of polymorphisms are increased which may
make it easier to demonstrate association between disease and a
chromosomal region. Second: The evolutionary process where genes are
inherited from ancestors is not independent between loci, why models
from population genetics can naturally be involved in association
analysis based on haplotypes.  To fully use the haplotype information,
the evolvement from the (unknown) founders until todays haplotypes are
included in the process. We try to model this by using population
genetics' models, such as the Ancestral Recombination Graph, as well
as approximate methods borrowed from spatial statistic.