Using advanced intercross lines for high-resolution mapping HDL cholesterol quantitative trait loci

Xiaosong Wang, Isabelle Le Roy, Edwige Nicodeme, Renhua Li, Richard Wagner, Christina Petros, Gary A. Churchill, Stephen Harris, Ariel Darvasi, Jorge Kirilovsky, Pierre L. Roubertoux, Beverly Paigen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


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/BINJ) × 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/BINJ)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 (Nrli3, 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.

Original languageEnglish
Pages (from-to)1654-1664
Number of pages11
JournalGenome Research
Issue number7
StatePublished - 1 Jul 2003
Externally publishedYes


Dive into the research topics of 'Using advanced intercross lines for high-resolution mapping HDL cholesterol quantitative trait loci'. Together they form a unique fingerprint.

Cite this