Genetic regulation of cholesterol homeostasis: Chromosomal organization of candidate genes

Carrie L. Welch, Yu Rong Xia, Ishaiahu Shechter, Robert Farese, Margarete Mehrabian, Shahab Mehdizadeh, Craig H Warden, Aldons J. Lusis

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

As part of an effort to dissect the genetic factors involved in cholesterol homeostasis in the mouse model, we report the mapping of 12 new candidate genes using linkage analysis. The genes include: cytoplasmic HMG- CoA synthase (Hmgcs1, Chr 13), mitochondrial synthase (Hmgcs2, Chr 3), a synthase-related sequence (Hmgcs1-rs, Chr 12), mevalonate kinase (Mvk, Chr 5), farnesyl diphosphate synthase (Fdps, Chr 3), squalene synthase (Fdft1, Chr 14), acyl-CoA:cholesterol acyltransferase (Acact, Chr 1), sterol regulatory element binding protein-1 (Srebf1, Chr 8) and -2 (Srebf2, Chr 15), apolipoprotein A-I regulatory protein (Tcfcoup2, Chr 7), low density receptor-related protein-related sequence (Lrp-rs, Chr 10), and Lrp- associated protein (Lrpap1, Chr 5). In addition, the map positions for several lipoprotein receptor genes were refined. These genes include: low density lipoprotein receptor (Ldlr, Chr 9), very low density lipoprotein receptor (Vldlr, Chr 19), and glycoprotein 330 (Gp330, Chr 2). Some of these candidate genes are located within previously defined chromosomal regions (quantitative trait loci, QTLs) contributing to plasma lipoprotein levels, and Acact maps near a mouse mutation, ald, resulting in depletion of cholesteryl esters in the adrenals. The combined use of QTL and candidate gene mapping provides a powerful means of dissecting complex traits such as cholesterol homeostasis.

Original languageEnglish (US)
Pages (from-to)1406-1421
Number of pages16
JournalJournal of Lipid Research
Volume37
Issue number7
StatePublished - Jul 1996

Keywords

  • cholesterol metabolism
  • complex trait
  • conserved synteny
  • disease gene
  • quantitative trait locus

ASJC Scopus subject areas

  • Endocrinology

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    Welch, C. L., Xia, Y. R., Shechter, I., Farese, R., Mehrabian, M., Mehdizadeh, S., Warden, C. H., & Lusis, A. J. (1996). Genetic regulation of cholesterol homeostasis: Chromosomal organization of candidate genes. Journal of Lipid Research, 37(7), 1406-1421.