Ag. Clark et al., HAPLOTYPE STRUCTURE AND POPULATION GENETIC INFERENCES FROM NUCLEOTIDE-SEQUENCE VARIATION IN HUMAN LIPOPROTEIN-LIPASE, American journal of human genetics, 63(2), 1998, pp. 595-612
Allelic variation in 3.7 kb of genomic DNA sequence from the human lip
oprotein lipase gene (LPL) was scored in 71 healthy individuals (142 c
hromosomes) from three populations: African Americans (24) from Jackso
n, MS; Finns (24) from North Karelia, Finland; and non-Hispanic Whites
(23) from Rochester, MN. The sequences had a total of 88 variable sit
es, with a nucleotide diversity (site-specific heterozygosity) of .002
+/- .001 across this 9.7-kb region. The frequency spectrum of nucleot
ide variation exhibited a slight excess of heterozygosity, but, in gen
eral, the data fit expectations of the infinite-sites model of mutatio
n 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. Des
pite the strong evidence for recombination, extensive linkage disequil
ibrium was observed. The number of haplotypes generally is much greate
r than the number expected under the infinite-sites model, but there w
as sufficient multisite linkage disequilibrium to reveal two major cla
des, which appear to be very old. Variation in this region of LPL may
depart from the variation expected under a simple, neutral model, owin
g to complex historical patterns of population founding, drift, select
ion, and recombination. These data suggest that the design and interpr
etation of disease-association studies may not be as straightforward a
s often is assumed.