genetics and evolution of lactose (in)tolerance
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Topics to cover What is Lactose intolerance
Causes Symptoms Diagnosis Lactose supplementation
LCT gene Lactase Affect of MCM6
Evolution 2 hypotheses mutations based on locations
What is lactose intolerance
The inability or insufficient ability to digest lactose
Body can’t produce lactase
Causes Primary lactase deficiency
Develops over time Body begins to produce less lactase. Inheritable
Secondary lactase deficiency results from injury to the small intestine
Severe diarrheal illness Celiac disease Crohn's disease Chemotherapy.
Congenital lactase deficiency Autosomal recessive Rare Prevents lactase expression from birth
Symptoms of intolerance
Can be mild or severe
30 minutes – 2 hours
Bloating
Pain or cramps in lower belly
Gas
Loose stools or diarrhea
Throwing up or nausea
Diagnosis
Hydrogen Breath Test High levels of Hydrogen if lactose is undigested
Stool Acidity Test Undigested lactose creates lactic acid and
other fatty acids that can be detected in a stool sample.
Blood test Measures blood glucose levels Take blood every 10-15 minutes Higher levels means lactose is digested
Lactase supplementation
Produced by fungi of the genus Asoergillus Functions well in high-acid
environments Must reach small intestine
before food does
Yeast from genus Kluyveromyces Takes longer to act Destroyed by mild acidic
environments Used in producing lactose free
and lactose reduced products
Long (q) arm of Chromosome 2 at position 21 Cytogenetic Location: 2q21 Molecular Location on chromosome 2:
base pairs 135,787,844 to 135,837,179
Encodes for an enzyme with lactase phlorizin hydrolase activity
LCT gene
Lactase
LPH/Beta-galactosidase
Enzyme that Digests lactose
Produced by epithelial cells that line the walls of the small intestine.
Lactase functions at the brush border Groups of microvilli
Mutation that causes persistence
Lactase persistence is autosomal dominant
Mutation is 14 kb chromosomally upstream in the MCM6 gene 97% in Adult cases Enhances the production of LPH mRNA
There are six identified allelic variants of the MCM6 gene associated with lactase persistence
C/T-13910 mutation Mutation G/A-22018 is in co-segregation with it
Evolution
Lactose persistence (LP) European, African and Middle Eastern
populations
Highest in Northern Europe Frequencies of LP genotype range from
71-79.8%
LP was low/absent in most European Neolithic populations
LP selection occurred between 3000 BC- AD 1200
2 hypothesis Genetic drift
Culture-historical/ selection
Genetic pressures Easily stored Milk as a source of water Increased calcium absorption
Rickets and osteomalacia
Mutations based on location
Mutations in Northern European population C→T-13910
G/A-22018
Mutations in Middle Eastern populations T/G-13915
Mutations in African populations C/G-13907 T/G-13915 G/C-14010
LP phenotype frequencies based on frequency data for the currently known LP associated allelic variants, excluding
the -13,910 C>T allele
Portugal Genotyped 13910 C>T in north, central and south and
subjects with gastrointestinal symptoms
Frequencies Center- 0.393 North-0.383 South- 0.269 Symptomatic group- 0.363
NOT UNIFORM
Found genotyping is a good diagnostic tool in the Portuguese population
self-reported gastrointestinal complaints are not good predictors of the LP status
Fun facts Infants born prematurely are more
likely to have lactase deficiency because an infant's lactase levels do not increase until the third trimester of pregnancy.
Lactose can also be present in bread, baked goods, salad dressings, candies, potato and corn chips.
In Caucasians only about 15% develop lactose intolerance while 80-90% of the African American and Asian populations are affected.
Compared to other mammalian species, human milk has the highest concentration of the disaccharide lactose