Identification of a mutation in the low density lipoprotein receptor gene associated with recessive familial hypercholesterolemia in swine. Academic Article uri icon

abstract

  • Elevated blood plasma cholesterol (hypercholesterolemia) is a major risk factor for coronary artery disease (CAD) in humans. Genetic dissection of polygenic lipid and lipoprotein disorders in swine, a key animal model for the study of familial hypercholesterolemia (FH) and CAD, led to the isolation of a monogenic subphenotype (FH-r), that is inherited in the recessive (r) manner. A genome scan mapped the FH-r locus close to the centromere of chromosome 2. Comparative mapping showed that this region shares homology with a part of human chromosome 19 that harbors the low density lipoprotein receptor (LDLR) locus, and therefore suggested LDLR as the prime candidate gene for FH-r. Cloning and sequencing of hepatic LDLR cDNA from two FH-r/r and one normal (N/N) animals disclosed a single missense mutation (R84C) in a region that corresponds to human exon 4. The C84 mutation cosegregates invariantly with hypercholesterolemia, which strongly suggests that this mutation is responsible for the observed hyperlipidemia.

published proceedings

  • Am J Med Genet

altmetric score

  • 6

author list (cited authors)

  • Hasler-Rapacz, J., Ellegren, H., Fridolfsson, A. K., Kirkpatrick, B., Kirk, S., Andersson, L., & Rapacz, J.

citation count

  • 96

complete list of authors

  • Hasler-Rapacz, J||Ellegren, H||Fridolfsson, AK||Kirkpatrick, B||Kirk, S||Andersson, L||Rapacz, J

publication date

  • April 1998

publisher