Fine mapping of Hyplip1 and the human homolog, a potential locus for FCHL.
Familial combined hyperlipidemia (FCHL) is a common genetic dyslipidemia predisposing to premature coronary heart disease (CHD). We previously identified a locus for FCHL on human Chromosome (Chr) 1q21-q23 in 31 Finnish FCHL families. We also mapped a gene for combined hyperlipidemia (Hyplip1) to a potentially orthologous region of mouse Chr 3 in the HcB-19/Dem mouse model of FCHL. The human FCHL locus was, however, originally mapped about 5 Mb telomeric to the synteny border, the centromeric part of which is homologous to mouse Chr 3 and the telomeric part to mouse Chr 1. To further localize the human Hyplip1 homolog and estimate its distance from the peak linkage markers, we fine-mapped the Hyplip1 locus and defined the borders of the region of conserved synteny between human and mouse. This involved establishing a physical map of a bacterial artificial chromosome (BAC) contig across the Hyplip1 locus and hybridizing a set of BACs to both human and mouse chromosomes by fluorescence in situ hybridization (FISH). We narrowed the location of the mouse Hyplip1 gene to a 1.5-cM region that is homologous only with human 1q21 and within approximately 5-10 Mb of the peak marker for linkage to FCHL. FCHL is a complex disorder and this distance may, thus, reflect the well-known problems hampering the mapping of complex disorders. Further studies identifying and sequencing the Hyplip1 gene will show whether the same gene predisposes to hyperlipidemia in human and mouse.
Pajukanta
P
P
UCLA, Department of Human Genetics, Gonda Neuroscience and Genetics Research Center, Los Angeles, California 90095-7088, USA.
Bodnar
J S
JS
Sallinen
R
R
Chu
M
M
Airaksinen
T
T
Xiao
Q
Q
Castellani
L W
LW
Sheth
S S
SS
Wessman
M
M
Palotie
A
A
Sinsheimer
J S
JS
Demant
P
P
Lusis
A J
AJ
Peltonen
L
L
D000818:Animals; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial; D020451:Contig Mapping; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008807:Mice, Inbred BALB C; D018895:Microsatellite Repeats