DNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene


Lipoprotein 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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Figure 1: A schematic diagram of the human LPL gene.
Figure 2: Novel DNA variants identified in LPL using sequence analysis.
Figure 3: Comparison of observed and expected heterozygosities.
Figure 4: A plot of the heterozygosity for the 88 variant sites found in the LPL sequence.
Figure 5: Comparison of the 71 individuals to the reference LPL sequence for the 88 variant sites.


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We thank Q. Deng and V. Tobe for their assistance in obtaining the human LPL sequences, and M. Olson, D. Burke and P. Green for their advice and encouragement. This work was accomplished with support from the National Heart, Blood, and Lung Institute (HL58238, -39 & -40, HL39107) and the National Science Foundation (DIR 8809710).

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Correspondence to Deborah A. Nickerson.

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Nickerson, D., Taylor, S., Weiss, K. et al. DNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene. Nat Genet 19, 233–240 (1998). https://doi.org/10.1038/907

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