title: Haplotype analysis at the low density lipoprotein receptor locus in normal and familial hypercholesterolemia Norwegian subjects.
abstract: We have performed haplotype analysis at the low density lipoprotein receptor (LDLR) locus in order to investigate the molecular genetics of familial hypercholesterolemia (FH) in Norway. Haplotypes were constructed using 7 restriction fragment length polymorphisms (RFLPs) in 194 subjects from 48 unrelated Norwegian FH families. Hypercholesterolemia co-segregated with haplotypes at the LDLR locus in all 48 families. Unambiguous haplotypes could be established for 190 independent chromosomes from 51 FH heterozygotes and 44 healthy normal subjects. A total of 20 different haplotypes was found. The most frequent haplotype was haplotype 3, which accounted for 32.4% or 43.1% of the normal and defective haplotypes, respectively. Haplotype 2 was significantly more frequent among the defective alleles than among the normal alleles (33.3% and 5.8%, respectively, p < 0.0001). Thus, haplotypes 2 and 3 accounted for 76.4% of the defective haplotypes. More data are needed to determine the possible existence of founder genes in the Norwegian population. Haplotypes 1, 2, 3, 5 and 8 accounted for 88.2% of the normal haplotypes. Based upon the cumulative heterozygosity index, the SphI, NcoI and 3' ApaLI RFLPs are the most informative markers in the Norwegian population.
authors.affiliation: Department of Medical Genetics, Ullevål University Hospital, Oslo, Norway.
authors.forename: O K
authors.initials: OK
authors.lastname: Rødningen
authors.forename: T P
authors.initials: TP
authors.lastname: Leren
authors.forename: O
authors.initials: O
authors.lastname: Røsby
authors.forename: S
authors.initials: S
authors.lastname: Tonstad
authors.forename: L
authors.initials: L
authors.lastname: Ose
authors.forename: K
authors.initials: K
authors.lastname: Berg
mesh_terms: D001483:Base Sequence; D015139:Blotting, Southern; D005190:Family; D006580:Genetic Carrier Screening; D006239:Haplotypes; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis / Q000235:genetics*; D008969:Molecular Sequence Data; D009664:Norway; D012150:Polymorphism, Restriction Fragment Length; D011973:Receptors, LDL / Q000737:chemistry / Q000235:genetics*
chemical_list: D011973:Receptors, LDL