An experimental assessment of in silico haplotype association mapping in laboratory mice. BMC Genet 2009 Dec 09;10:81
Date
12/17/2009Pubmed ID
20003225Pubmed Central ID
PMC2797012DOI
10.1186/1471-2156-10-81Scopus ID
2-s2.0-73249149539 (requires institutional sign-in at Scopus site) 20 CitationsAbstract
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.
Author List
Burgess-Herbert SL, Tsaih SW, Stylianou IM, Walsh K, Cox AJ, Paigen BAuthor
Shirng-Wern Tsaih Research Scientist II in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AllelesAnimals
Cholesterol, HDL
Computational Biology
Erythrocyte Count
Female
Haplotypes
Male
Mice
Mice, Inbred Strains
Quantitative Trait Loci
