RT Journal
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
JF Genome Research 
JO Genome Research 
YR 2003 
FD July 01 
VO 13 
IS 7 
SP 1654 
OP 1664 
DO 10.1101/gr.1185803 
UL http://genome.cshlp.org/content/13/7/1654.abstract 
AB 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.