Lactase persistence no relation Sudan
Genetics
Multiple studies indicate that the presence of the two phenotypes "lactase persistent" (derived phenotype) and "lactase nonpersistent" (hypolactasia) is genetically programmed, and that lactase persistence is not necessarily conditioned by the consumption of lactose after the suckling period.The lactase persistent phenotype involves high mRNA expression, high lactase activity, and thus the ability to digest lactose, while the lactase nonpersistent phenotype involves low mRNA expression and low lactase activity. The enzyme lactase is encoded by the gene LCT.Hypolactasia is known to be recessively and autosomally inherited, which means that individuals with the nonpersistent phenotype are homozygous and received the two copies of a low lactase-activity allele (the ancestral allele) from their parents, who may be homozygous or at least heterozygous for the allele. Only one high-activity allele is required to be lactase persistent. Lactase persistence behaves as a dominant trait because half levels of lactase activity are sufficient to show significant digestion of lactose. Cis-acting transcriptional silence of the lactase gene is responsible for the hypolactasia phenotype. Furthermore, studies show that only eight cases were found where the parents of a child with lactase persistence were both hypolactasic. While a variety of genetic, as well as nutritional, factors determine lactase expression, no evidence has been found for adaptive alteration of lactase expression within an individual in response to changes in lactose consumption levels. The two distinct phenotypes of hypolactasia are: Phenotype I, characterized by reduced synthesis of precursor LPH, and phenotype II, associated with ample precursor synthesis, but reduced conversion of the protein to its mature molecular form.
The lactase enzyme has two active sites which break down lactose. The first is at Glu1273 and the second is at Glu1749, which separately break down lactose into two separate kinds of molecules.At least six mutations (single-nucleotide polymorphisms – SNPs) have been associated with lactase expression. They are all located in a region of the gene MCM6 upstream of LCT. This region is considered as an enhancer region for the transcription of LCT. The first identified genetic variant associated with lactase persistence is C/T*−13910. The ancestral allele is C and the derived allele – associated with lactase persistence – is T. In the same study, another variant was found to also correlate with the phenotype in most of the cases: G*/A-22018.
Other alleles associated with lactase persistence have been identified: G/C*-14010, C/G*-13907, and T/G*-13915. This variant is described as part of a compound allele with T/C*3712 in. These three variants are widespread in some populations. Rare variants were reported in a few studies, like the G/A*14107 in the Xhosa and the Fulani (from Mali); the C/T*13906 in the Fulani (from Mali).Lactase-persistence alleles vary in their geographic distributions. Within European and populations of European ancestry, they are almost entirely correlated with the presence of the −13,910 C/T mutation in the enhancer region of the lactase gene (LCT).
This differs from lactase persistence allelic distributions in the rest of the world, particularly in Africa and in the Middle East, where several alleles coexist.
The T/G*-13915 allele is found mostly in populations from East and North Africa and the Middle East. The allele G/C*-14010 was identified in East Africa. The C/G*13907 allele was described in Sudan and Ethiopia. The "European" allele T*13910 allele is also found in some populations from Africa, including the Fulani (from Mali, Sudan, and Cameroon) and the Khoe from South Africa. This allele has also been found in Central Asia.It is not known how exactly the different variants described above regulate LCT expression. None of the mutations so far identified have been shown to be exclusively causal for lactase persistence, and it is possible that there are more alleles to be discovered. If we focus on the "European variant", the position −13910 has an enhancer function on the lactase promoter (the promoter facilitates the transcription of the LCT gene). T−13910 is a greater enhancer than C−13910, so this mutation is thought to be responsible for the differences in lactase expression, although not enough evidence is found to prove that lactase persistence is only caused by C−13910→T−13910.In addition, it was shown in one study involving a Finnish population that the lactase gene has a higher expression when G−22018 is combined with T-13910.
no relation