LCTMCM6

LCTMCM6 refers to a genomic region on human chromosome 2 that encompasses the lactase (LCT) gene and the adjacent MCM6 gene. The region is notable for regulatory elements within MCM6 that influence the expression of the LCT gene, enabling lactase production in adulthood in some human populations and giving rise to the trait known as lactase persistence.

Location and function: LCT and MCM6 lie close together on chromosome 2q21. An enhancer element located within intron 13 of MCM6 modulates LCT transcription in intestinal enterocytes. Variation in this regulatory region can determine whether lactase remains active after weaning.

Genetic variation: The most studied polymorphisms are single-nucleotide variants in MCM6 intron 13, including rs4988235, often described as the -13910 C>T variant, and rs182549. The T allele at rs4988235 (and related alleles) is associated with continued lactase expression into adulthood in many populations, whereas the C allele is linked to lactase non-persistence.

Population genetics and evolution: The distribution of lactase-persistence alleles in the LCTMCM6 region shows signals of recent positive selection in populations with a long history of dairy consumption. The region is widely used to study demographic history, migration, and the spread of dairy culture.

Clinical and research relevance: Variation in LCTMCM6 explains a substantial portion of interindividual and interpopulation differences in adult lactose tolerance. It serves as a prominent example of regulatory evolution, illustrating how non-coding variants can influence metabolic traits.