Nature Genetics
19, 233 - 240 (1998)
doi:10.1038/907
DNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase
geneDeborah A. Nickerson1, Scott L. Taylor1, Kenneth M. Weiss2, Andrew G. Clark3, Richard G. Hutchinson4, Jari Stengård5, Veikko Salomaa5, Erkki Vartiainen5, Eric Boerwinkle6
& Charles F. Sing71
Department of Molecular Biotechnology, Box 357730,
University of Washington, Seattle, Washington
98125, USA. 2
Department of Anthropology, Pennsylvania State University,
University Park, Pennsylvania 16802, USA. 3
Institute of Molecular Evolutionary Genetics, Department
of Biology, Pennsylvania State University, University Park,
Pennsylvania 16802, USA. 4
Preventive Cardiology, University of Mississippi Medical
Center, Jackson, Mississippi 39216, USA. 5
National Public Health Institute, Department of Epidemiology
and Health Promotion, Helsinki, Finland. 6
Human Genetics Center, University of Texas Health Science
Center, Houston, Texas 77225, USA. 7
Department of Human Genetics, University of Michigan
Medical School, Ann Arbor, Michigan 48109, USA.
Correspondence should be addressed to Deborah A. Nickerson debnick@u.washington.eduLipoprotein lipase plays a central role in lipid metabolism and the
gene that encodes this enzyme (LPL) is a candidate susceptibility gene
for cardiovascular disease. Here we report the complete sequence of a fraction
of the LPL gene for 71 individuals (142 chromosomes) from three populations
that may have different histories affecting the organization of the sequence
variation. Eighty-eight sites in this 9.7 kb vary among individuals from these
three populations. Of these, 79 were single nucleotide substitutions and 9
sites involved insertion-deletion variations. The average nucleotide diversity
across the region was 0.2% (or on average 1 variable site every 500 bp). At
34 of these sites, the variation was found in only one of the populations,
reflecting the differing population and mutational histories. If LPL is
a typical human gene, the pattern of sequence variation that exists in introns
as well as exons, even for the small number of samples considered here, will
present challenges for the identification of sites, or combinations of sites,
that influence variation in risk of disease in the population at large.
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