An experimental assessment of in silico haplotype association mapping in laboratory mice.
Document Type
Article
Publication Date
2009
Keywords
Animals, Cholesterol-HDL, Computational-Biology, Erythrocyte-Count, Haplotypes, Mice-Inbred-Strains, Quantitative-Trait-Loci
First Page
81
Last Page
81
JAX Source
BMC Genet 2009; 10:81.
Abstract
BACKGROUND: To assess the utility of haplotype association mapping (HAM) as a quantitative trait locus (QTL) discovery tool, we conducted HAM analyses for red blood cell count (RBC) and high density lipoprotein cholesterol (HDL) in mice. We then experimentally tested each HAM QTL using published crosses or new F2 intercrosses guided by the haplotype at the HAM peaks. RESULTS: The HAM for RBC, using 33 classic inbred lines, revealed 8 QTLs; 2 of these were true positives as shown by published crosses. A HAM-guided (C57BL/6J x CBA/J)F2 intercross we carried out verified 2 more as true positives and 4 as false positives. The HAM for HDL, using 81 strains including recombinant inbred lines and chromosome substitution strains, detected 46 QTLs. Of these, 36 were true positives as shown by published crosses. A HAM-guided (C57BL/6J x A/J)F2 intercross that we carried out verified 2 more as true positives and 8 as false positives. By testing each HAM QTL for RBC and HDL, we demonstrated that 78% of the 54 HAM peaks were true positives and 22% were false positives. Interestingly, all false positives were in significant allelic association with one or more real QTL. CONCLUSION: Because type I errors (false positives) can be detected experimentally, we conclude that HAM is useful for QTL detection and narrowing. We advocate the powerful and economical combined approach demonstrated here: the use of HAM for QTL discovery, followed by mitigation of the false positive problem by testing the HAM-predicted QTLs with small HAM-guided experimental crosses.
Recommended Citation
Burgess HS,
Tsaih SW,
Stylianou IM,
Walsh K,
Cox AJ,
Paigen B.
An experimental assessment of in silico haplotype association mapping in laboratory mice. BMC Genet 2009; 10:81.