Polymorphic haplotypes and recombination rates at the LDL receptor gene locus in subjects with and without familial hypercholesterolemia who are from different populations

Item Type:	Article
Title:	Polymorphic haplotypes and recombination rates at the LDL receptor gene locus in subjects with and without familial hypercholesterolemia who are from different populations
Creators Name:	Miserez, A.R. and Schuster, H. and Chiodetti, N. and Keller, U.
Abstract:	RFLPs at the low-density lipoprotein (LDL) receptor locus for TaqI, StuI, HincII, AvaII, ApaLI (5' and 3'), PvuII, and NcoI were studied in Swiss and German families with familial hypercholesterolemia (FH). A total of 1,104 LDL receptor alleles were analyzed using Southern blotting and new PCR-based techniques for detection of the TaqI, StuI, HincII, AvaII, NcoI RFLPs. Two hundred fifty-six independent haplotypes from 368 individuals of 61 unrelated Swiss families, as well as 114 independent haplotypes from 184 subjects of 25 unrelated German families, were constructed. In 76 families, clinical diagnosis of FH was confirmed by cosegregation analysis. Of the 43 unique haplotypes consisting of seven RFLPs detected in the Swiss and Germans, only 9 were common in both population samples. Analysis of linkage disequilibrium revealed nonrandom associations between several of the investigated RFLPs. ApaLI (5'), NcoI, PvuII, TaqI, and AvaII or HincII were particularly informative (cumulative informativeness .85). Relative frequencies, heterozygosity indexes, and PICs of the RFLPs from the Swiss and Germans were compared with values calculated from reported haplotype data for Italians, Icelanders, North American Caucasians, South African Caucasians, and Japanese. Pairwise comparisons of population samples by common RFLPs demonstrated unexpected differences even between geographically adjacent populations (e.g., the Swiss and Germans). Furthermore, genetic distances from the Germans to the other Caucasians were larger than to the Japanese. An unexpected lack of correlation between linkage disequilibria and physical distances was detected for the German and Japanese data, possibly because of nonuniform recombination with excessively high rates between exon 13 and intron 15. Hence, the present study revealed a striking variety of polymorphic haplotypes and heterogeneity of RFLP frequencies and recombination rates among the seven population samples.
Keywords:	Base Sequence, Chi-Square Distribution, Continental Population Groups, DNA Mutational Analysis, DNA Restriction Enzymes, Ethnic Groups, Evolution, Gene Frequency, Genetic Variation, Population Genetics, Haplotypes, Hyperlipoproteinemia Type II, Linkage Disequilibrium, Genetic Models, Molecular Sequence Data, Pedigree, Restriction Fragment Length Polymorphism, LDL Receptors, Genetic Recombination
Source:	American Journal of Human Genetics
ISSN:	0002-9297
Publisher:	University of Chicago Press
Volume:	52
Number:	4
Page Range:	808-826
Date:	April 1993
Official Publication:	http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1682072/
PubMed:	View item in PubMed

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