Haplotype Structure and Population Genetic Inferences from Nucleotide-Sequence Variation in Human Lipoprotein Lipase

• Published in: American journal of human genetics Vol. 63; no. 2; pp. 595 - 612
• Main Authors: Clark, Andrew G., Weiss, Kenneth M., Nickerson, Deborah A., Taylor, Scott L., Buchanan, Anne, Stengård, Jari, Salomaa, Veikko, Vartiainen, Erkki, Perola, Markus, Boerwinkle, Eric, Sing, Charles F.
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01.08.1998; University of Chicago Press
• Subjects: African Continental Ancestry Group - genetics; Animals; Biological and medical sciences; Cytogenetics; European Continental Ancestry Group - genetics; Finland - ethnology; Fundamental and applied biological sciences. Psychology; Genetic Variation; Genetics of eukaryotes. Biological and molecular evolution; Genetics, Population; Genotype; Haplotypes; Heterozygote; Human; Humans; Linkage Disequilibrium; Lipoprotein lipase; Lipoprotein Lipase - genetics; LPL; Minnesota; Mississippi; Models, Genetic; Pan troglodytes - genetics; Polymerase Chain Reaction; Recombination, Genetic; Reference Values; Single-nucleotide polymorphism; Mississippi; Minnesota; Finland; LPL; Lipoprotein lipase; Single-nucleotide polymorphism; Genetic variation; Linkage disequilibrium; Human; Linkage; Nucleotide sequence; Enzyme; Negroid; Lipids; Exploration; Esterases; Linkage equilibrium; Ethnic group; Carboxylic ester hydrolases; Heterozygosity; English; Gene; Genetics; Hydrolases; Finnish; Black American; Caucasoid; Haplotype
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/301977

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.