THE LACTASE PERSISTENCE NON-PERSISTENCE POLYMORPHISM IS CONTROLLED BYA CIS-ACTING ELEMENT/

Lactase activity is present at high levels in the small intestine of s ome human adults and not others. This is due to a genetically determin ed polymorphism which affects the developmental regulation of the expr ession of the lactase gene. This polymorphism is of considerable inter est in relation to cultural differences in nutrition but despite exhau stive studies, the molecular basis has not yet been found, it has not even been shown whether the sequence differences reside within or adja cent to the lactase gene itself or in a trans-acting factor. We have t herefore exploited known DNA 'marker' polymorphisms within the exons o f the lactase gene to examine the expression of the individual lactase mRNA transcripts from persistent and non-persistent individuals in or der to determine whether the regulation is in cis or trans. Our result s show that in certain lactase persistent individuals one allele of th e lactase gene is expressed at much lower levels than the other and th ese individuals tend to have intermediate lactase activities. It is pr oposed that these people are heterozygous far the lactase persistence and non-persistence alleles and that this means that the nucleotide su bstitutions responsible for the lactase persistence/non-persistence po lymorphism are cis-acting. This narrows down considerably the area of the genome that needs to be searched for the relevant sequence differe nces.