Editing Lactase (section)

== Genetic expression and regulation ==
In humans, lactase is encoded by a single genetic locus on chromosome 2.<ref name = "pmid9148757">{{cite journal | vauthors = Troelsen JT, Mitchelmore C, Spodsberg N, Jensen AM, Norén O, Sjöström H | title = Regulation of lactase-phlorizin hydrolase gene expression by the caudal-related homoeodomain protein Cdx-2 | journal = The Biochemical Journal | volume = 322 | issue = Pt. 3 | pages = 833–8 | date = Mar 1997 | pmid = 9148757 | pmc = 1218263 | doi = 10.1042/bj3220833 }}</ref> It is expressed exclusively by mammalian small intestine enterocytes and in very low levels in the colon during fetal development.<ref name="pmid9148757"/> Humans are born with high levels of lactase expression. In most of the world's population, lactase transcription is down-regulated after weaning, resulting in diminished lactase expression in the small intestine,<ref name = "pmid9148757"/> which causes the common symptoms of adult-type hypolactasia, or lactose intolerance.<ref>{{cite web|url=https://ghr.nlm.nih.gov/gene/LCT|title=LCT gene|first=Genetics Home|last=Reference|website=Genetics Home Reference|access-date=3 April 2018}}</ref> The ''LCT'' gene provides the instructions for making lactase.  Lactose intolerance in infants (congenital lactase deficiency) is caused by mutations in the ''LCT'' gene. Mutations are believed to interfere with the function of lactase, causing affected infants to have a severely impaired ability to digest lactose in breast milk or formula.<ref name="medlineplus.gov">{{cite web |title=Lactose intolerance: MedlinePlus Genetics |url=https://medlineplus.gov/genetics/condition/lactose-intolerance/ |access-date=2022-03-22 |website=medlineplus.gov |language=en}}</ref>

Some population segments exhibit lactase persistence resulting from a mutation that is postulated to have occurred 5,000–10,000 years ago, coinciding with the rise of cattle domestication.<ref>{{cite journal | vauthors = Bersaglieri T, Sabeti PC, Patterson N, Vanderploeg T, Schaffner SF, Drake JA, Rhodes M, Reich DE, Hirschhorn JN | title = Genetic signatures of strong recent positive selection at the lactase gene | journal = American Journal of Human Genetics | volume = 74 | issue = 6 | pages = 1111–20 | date = Jun 2004 | pmid = 15114531 | pmc = 1182075 | doi = 10.1086/421051 }}</ref> This mutation has allowed almost half of the world's population to metabolize lactose without symptoms. Studies have linked the occurrence of lactase persistence to two different [[single-nucleotide polymorphism]]s about 14 and 22 kilobases upstream of the 5'-end of the LPH gene.<ref>{{cite journal | vauthors = Kuokkanen M, Enattah NS, Oksanen A, Savilahti E, Orpana A, Järvelä I | title = Transcriptional regulation of the lactase-phlorizin hydrolase gene by polymorphisms associated with adult-type hypolactasia | journal = Gut | volume = 52 | issue = 5 | pages = 647–52 | date = May 2003 | pmid = 12692047 | pmc = 1773659 | doi = 10.1136/gut.52.5.647 }}</ref> Both mutations, C→T at position -13910 and G→ A at position -22018, have been independently linked to lactase persistence.<ref name = "pmid15777735">{{cite journal | vauthors = Troelsen JT | title = Adult-type hypolactasia and regulation of lactase expression | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1723 | issue = 1–3 | pages = 19–32 | date = May 2005 | pmid = 15777735 | doi = 10.1016/j.bbagen.2005.02.003 }}</ref>

The lactase promoter is 150 base pairs long and is located upstream of the site of transcription initiation.<ref name = "pmid15777735"/> The sequence is highly conserved in mammals, suggesting that critical cis-transcriptional regulators are located nearby.<ref name = "pmid15777735"/> [[CDX2|Cdx-2]], [[HNF1A|HNF-1α]], and [[GATA transcription factor|GATA]] have been identified as transcription factors.<ref name = "pmid15777735"/> Studies of hypolactasia onset have demonstrated that despite polymorphisms, little difference exists in lactase expression in infants, showing that the mutations become increasingly relevant during development.<ref name = "pmid9609760">{{cite journal | vauthors = Wang Y, Harvey CB, Hollox EJ, Phillips AD, Poulter M, Clay P, Walker-Smith JA, Swallow DM | title = The genetically programmed down-regulation of lactase in children | journal = Gastroenterology | volume = 114 | issue = 6 | pages = 1230–6 | date = Jun 1998 | pmid = 9609760 | doi = 10.1016/S0016-5085(98)70429-9 | doi-access = free }}</ref> Developmentally regulated DNA-binding proteins may down-regulate transcription or destabilize mRNA transcripts, causing decreased LPH expression after weaning.<ref name = "pmid9609760"/>