title: Linkage of a gene for familial hypobetalipoproteinemia to chromosome 3p21.1-22.
abstract: Familial hypobetalipoproteinemia (FHBL) is an apparently autosomal dominant disorder of lipid metabolism characterized by less than fifth percentile age- and sex-specific levels of apolipoprotein beta (apobeta) and low-density lipoprotein-cholesterol. In a minority of cases, FHBL is due to truncation-producing mutations in the apobeta gene on chromosome 2p23-24. Previously, we reported on a four-generation FHBL kindred in which we had ruled out linkage of the trait to the apobeta gene. To locate other loci containing genes for low apobeta levels in the kindred, a genomewide search was conducted. Regions on 3p21.1-22 with two-point LOD scores >1.5 were identified. Additional markers were typed in the region of these signals. Two-point LOD scores in the region of D3S2407 increased to 3.35 at O = 0. GENEHUNTER confirmed this finding with an nonparametric multipoint LOD score of 7.5 (P=.0004). Additional model-free analyses were conducted with the square root of the apobeta level as the phenotype. Results from the Loki and SOLAR programs further confirmed linkage of FHBL to 3p21.1-22. Weaker linkage to a region near D19S916 was also indicated by Loki and SOLAR. Thus, a heretofore unidentified genetic susceptibility locus for FHBL may reside on chromosome 3.
authors.affiliation: Washington University School of Medicine, Washington University, St. Louis, MO 63110, USA.
authors.forename: B
authors.initials: B
authors.lastname: Yuan
authors.forename: R
authors.initials: R
authors.lastname: Neuman
authors.forename: S H
authors.initials: SH
authors.lastname: Duan
authors.forename: J L
authors.initials: JL
authors.lastname: Weber
authors.forename: P Y
authors.initials: PY
authors.lastname: Kwok
authors.forename: N L
authors.initials: NL
authors.lastname: Saccone
authors.forename: J S
authors.initials: JS
authors.lastname: Wu
authors.forename: K Y
authors.initials: KY
authors.lastname: Liu
authors.forename: G
authors.initials: G
authors.lastname: Schonfeld
mesh_terms: D000293:Adolescent; D000368:Aged; D001055:Apolipoproteins B / Q000097:blood / Q000235:genetics; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000097:blood / Q000235:genetics*; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D010375:Pedigree; D019655:Quantitative Trait, Heritable; D012984:Software
chemical_list: D001055:Apolipoproteins B; D005819:Genetic Markers