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PMID: 9683608 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Haplotype structure and population genetic inferences from nucleotide-sequence variation in human lipoprotein lipase.

American journal of human genetics ·Vol. 63 ·No. 2 ·1998-08-00 ·Pages 595-612

Clark AG, Weiss KM, Nickerson DA, Taylor SL, Buchanan A, Stengård J, Salomaa V, Vartiainen E, Perola M, Boerwinkle E, Sing CF

Abstract

Allelic variation in 9.7 kb of genomic DNA sequence from the human lipoprotein lipase gene (LPL) was scored in 71 healthy individuals (142 chromosomes) from three populations: African Americans (24) from Jackson, MS; Finns (24) from North Karelia, Finland; and non-Hispanic Whites (23) from Rochester, MN. The sequences had a total of 88 variable sites, with a nucleotide diversity (site-specific heterozygosity) of .002+/-.001 across this 9.7-kb region. The frequency spectrum of nucleotide variation exhibited a slight excess of heterozygosity, but, in general, the data fit expectations of the infinite-sites model of mutation and genetic drift. Allele-specific PCR helped resolve linkage phases, and a total of 88 distinct haplotypes were identified. For 1,410 (64%) of the 2,211 site pairs, all four possible gametes were present in these haplotypes, reflecting a rich history of past recombination. Despite the strong evidence for recombination, extensive linkage disequilibrium was observed. The number of haplotypes generally is much greater than the number expected under the infinite-sites model, but there was sufficient multisite linkage disequilibrium to reveal two major clades, which appear to be very old. Variation in this region of LPL may depart from the variation expected under a simple, neutral model, owing to complex historical patterns of population founding, drift, selection, and recombination. These data suggest that the design and interpretation of disease-association studies may not be as straightforward as often is assumed.

MeSH Terms
Animals Blacks/genetics Finland/ethnology Genetic Variation Genetics, Population Genotype Haplotypes Heterozygote Humans Linkage Disequilibrium Lipoprotein Lipase/genetics Minnesota Mississippi Models, Genetic Pan troglodytes/genetics Polymerase Chain Reaction Recombination, Genetic Reference Values Whites/genetics
Chemicals
Lipoprotein Lipase
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Clark A G
Institute of Molecular Evolutionary Genetics, Department of Biology, Pennsylvania State University, University Park, PA 16802, USA. [email protected]
Weiss K M
Nickerson D A
Taylor S L
Buchanan A
Stengård J
Salomaa V
Vartiainen E
Perola M
Boerwinkle E
Sing C F
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
DOI
10.1086/301977
Email
[email protected]
Published
1998-08-00
Pages
595-612
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1377318
Subset
IM
Grants
NHLBI NIH HHS · HL39107 · United States
NHLBI NIH HHS · HL58238 · United States
NHLBI NIH HHS · HL58239 · United States
External Links
PubMed source DOI: 10.1086/301977 PMC Full Text View journal details
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