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Haplotype analysis at the low density lipoprotein receptor locus in normal and familial hypercholesterolemia Norwegian subjects
Author(s) -
Rødningen Olaug K.,
Leren Trond P.,
Røsby Oddveig,
Tonstad Serena,
Ose Leiv,
Berg Kare
Publication year - 1993
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.1993.tb03883.x
Subject(s) - haplotype , genetics , familial hypercholesterolemia , locus (genetics) , restriction fragment length polymorphism , biology , allele , population , loss of heterozygosity , allele frequency , genotype , endocrinology , gene , medicine , cholesterol , environmental health
Rødningen OK, Leren TP, Røsby O, Tonstad S, Ose L, Berg K. Haplotype analysis at the low density lipoprotein receptor locus in normal and familial hypercholesterolemia Norwegian subjects. Clin Genet 1993: 44: 214–220. © Munksgaard, 1993 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.