J. Haslerrapacz et al., IDENTIFICATION OF A MUTATION IN THE LOW-DENSITY-LIPOPROTEIN RECEPTOR GENE ASSOCIATED WITH RECESSIVE FAMILIAL HYPERCHOLESTEROLEMIA IN SWINE, American journal of medical genetics, 76(5), 1998, pp. 379-386
Elevated blood plasma cholesterol (hypercholesterolemia) is a major ri
sk factor for coronary artery disease (CAD) in humans, Genetic dissect
ion of polygenic lipid and lipoprotein disorders in swine, a key anima
l model for the study of familial hypercholesterolemia (FH) and CAD, l
ed to the isolation of a monogenic subphenotype (FH-r), that is inheri
ted in the recessive (r) manner, A genome scan mapped the FH-r locus c
lose to the centromere of chromosome 2, Comparative mapping showed tha
t this region shares homology with a part of human chromosome 19 that
harbors the low density lipoprotein receptor (LDLR) locus, and therefo
re suggested LDLR as the prime candidate gene for FH-r, Cloning and se
quencing of hepatic LDLR cDNA from two FH-r/r and one normal (N/N) ani
mals disclosed a single missense mutation (R84C) in a region that corr
esponds to human exon 4, The C84 mutation cosegregates invariantly wit
h hypercholesterolemia, which strongly suggests that this mutation is
responsible for the observed hyperlipidemia. (C) 1998 Wiley-Liss, Inc.