TY - JOUR A1 - Wang, Xiaosong A1 - Le Roy, Isabelle A1 - Nicodeme, Edwige A1 - Li, Renhua A1 - Wagner, Richard A1 - Petros, Christina A1 - Churchill, Gary A. A1 - Harris, Stephen A1 - Darvasi, Ariel A1 - Kirilovsky, Jorge A1 - Roubertoux, Pierre L. A1 - Paigen, Beverly T1 - Using Advanced Intercross Lines for High-Resolution Mapping of HDL Cholesterol Quantitative Trait Loci Y1 - 2003/07/01 JF - Genome Research JO - Genome Research SP - 1654 EP - 1664 DO - 10.1101/gr.1185803 VL - 13 IS - 7 UR - http://genome.cshlp.org/content/13/7/1654.abstract N2 - Mapping quantitative trait loci (QTLs)with high resolution facilitates identification and positional cloning of the underlying genes. The novel approach of advanced intercross lines (AILs) generates many more recombination events and thus can potentially narrow QTLs significantly more than do conventional backcrosses and F2 intercrosses. In this study, we carried out QTL analyses in (C57BL/6J × NZB/BlNJ)× C57BL/6J backcross progeny fed either chow or an atherogenic diet to detect QTLs that regulate high-density lipoprotein cholesterol (HDL)concentrations, and in (C57BL/6J × NZB/BlNJ)F11 AIL progeny to confirm and narrow those QTLs. QTLs for HDL concentrations were found on chromosomes 1, 5, and 16. AIL not only narrowed the QTLs significantly more than did a conventional backcross but also resolved a chromosome 5 QTL identified in the backcross into two QTLs, the peaks of both being outside the backcross QTL region. We tested 27 candidate genes and found significant mRNA expression differences for 12 (Nr1i3, Apoa2, Sap, Tgfb2, Fgfbp1, Prom, Ppargc1, Tcf1, Ncor2, Srb1, App, and Ifnar). Some of these underlay the same QTL, indicating that expression differences are common and not sufficient to identify QTL genes. All the major HDL QTLs in our study had homologous counterparts in humans, implying that their underlying genes regulate HDL in humans. ER -