title: Familial combined hyperlipidaemia linked to the apolipoprotein AI-CII-AIV gene cluster on chromosome 11q23-q24.
abstract: Familial combined hyperlipidaemia (FCHL) is a common inherited disorder of lipid metabolism with a prevalence of 0.5-2.0% (refs 1, 2). It is estimated to cause 10% of premature coronary heart disease. The underlying metabolic and genetic defects in FCHL have not been identified, but a population study has suggested an association between FCHL and an XmnI restriction fragment length polymorphism (RFLP) within the apolipoprotein AI-CIII-AIV gene cluster. Here we confirm this association and show that it results from linkage disequilibrium between FCHL and the 6.6-kilobase (kb) allele of the XmnI RFLP. Subsequent analysis in seven FCHL families, ascertained through a proband carrying the 6.6 kb XmnI allele, demonstrated linkage to the AI-CIII-AIV cluster on 11q23-q24, zeta = 6.86 with no recombinants. This assignment will facilitate the identification of the mutation that causes hyperlipidaemia in these families.
authors.affiliation: Division of Molecular Medicine, MRC Clinical Research Centre, Northwich Park Hospital, Harrow, Middlesex, UK.
authors.forename: A P
authors.initials: AP
authors.lastname: Wojciechowski
authors.forename: M
authors.initials: M
authors.lastname: Farrall
authors.forename: P
authors.initials: P
authors.lastname: Cullen
authors.forename: T M
authors.initials: TM
authors.lastname: Wilson
authors.forename: J D
authors.initials: JD
authors.lastname: Bayliss
authors.forename: B
authors.initials: B
authors.lastname: Farren
authors.forename: B A
authors.initials: BA
authors.lastname: Griffin
authors.forename: M J
authors.initials: MJ
authors.lastname: Caslake
authors.forename: C J
authors.initials: CJ
authors.lastname: Packard
authors.forename: J
authors.initials: J
authors.lastname: Shepherd
mesh_terms: D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A / Q000235:genetics*; D001056:Apolipoproteins C / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11; D005787:Gene Frequency; D008040:Genetic Linkage; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000235:genetics*; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A; D001056:Apolipoproteins C; D015345:Oligonucleotide Probes; C022205:apolipoprotein A-IV