A genetic polymorphism is responsible for determining that some
humans express lactase at high
levels throughout their lives and are thus lactose tolerant, while others
lose lactase expression during
childhood and are lactose intolerant. We have previously shown that this
polymorphism is controlled
by an element or elements which act in cis to the lactase gene. We have
also reported that 7
polymorphisms in the lactase gene are highly associated and lead to only
3 common haplotypes (A,
B and C) in individuals of European extraction. Here
we report the frequencies of these
polymorphisms in Caucasians from north and south Europe and also from the
Indian sub-continent,
and show that the alleles differ in frequency, the B and C
haplotypes being much more common in
southern Europe and India. Allelic association studies with lactase persistence
and non-persistence
phenotypes show suggestive evidence of association of lactase persistence
with certain alleles. This
association was rather more clear in the analysis of small families, where
haplotypes could be
determined. Furthermore haplotype and RNA transcript analysis of 11 unrelated
lactase persistent
individuals shows that the persistence (highly expressed) allele is almost
always on the A haplotype
background. Non-persistence is found on a variety of haplotypes including
A. Thus it appears that
lactase persistence arose more recently than the DNA marker polymorphisms
used here to define the
main Caucasian haplotypes, possibly as a single mutation on the A
haplotype background. The high
frequency of the A haplotype in northern Europeans is consistent
with the high frequency of lactase
persistence.