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BMC Genetics

, 10:81

First Online: 09 December 2009Received: 18 February 2009Accepted: 09 December 2009

Abstract

BackgroundTo 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.

ResultsThe 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 × CBA-JF2 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 × A-JF2 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.

ConclusionBecause 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.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2156-10-81 contains supplementary material, which is available to authorized users.

Sarah L Burgess-Herbert, Shirng-Wern Tsaih contributed equally to this work.

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Autor: Sarah L Burgess-Herbert - Shirng-Wern Tsaih - Ioannis M Stylianou - Kenneth Walsh - Allison J Cox - Beverly Paigen

Fuente: https://link.springer.com/article/10.1186/1471-2156-10-81







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