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.
UCLA, Department of Human Genetics, Gonda Neuroscience and Genetics Research Center, Los Angeles, California 90095-7088, USA.
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Pajukanta
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Bodnar
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Sallinen
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Chu
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Airaksinen
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Xiao
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Castellani
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Sheth
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Wessman
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Palotie
J S
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Sinsheimer
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Demant
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Lusis
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Peltonen
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