Limits on fine mapping of complex traits
We recently published a paper in the journal on high-resolution genetic mapping of complex traits. In that paper, we considered the confidence region for the position of a gene localized by genetic mapping. We showed that the size of this confidence region increases rapidly as the trait becomes more complex (that is, as the relative risk or the proportion of alleles shared by affected relatives decreases). We concluded that using affected-relative-pair analysis to localize a gene conferring a modest increased risk to a region suitable for positional cloning (e.g., 1 cM) requires a large number of relative pairs (or, more generally, meioses). Since the paper appeared, we have discovered an intuitive way to understand the difficulty of fine mapping of susceptibility genes for complex traits. The insight was motivated by a colleague who inquired why one could not simply confine the search for a susceptibility gene to the region of maximum allele sharing in a sib-pair (or other relative pair) data set. The key question is thus: what is the chance that susceptibility gene will not be in the region of maximum allele sharing? The answer is easily obtained by using the methods described in our previous paper. 3 refs.
- OSTI ID:
- 273506
- Journal Information:
- American Journal of Human Genetics, Vol. 58, Issue 5; Other Information: PBD: May 1996
- Country of Publication:
- United States
- Language:
- English
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