genetics and evolution of lactose (in)tolerance

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Genetics and Evolution of lactose (in)tolerance By: Tracy Adkins

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Genetics and Evolution of lactose (in)tolerance

By: Tracy Adkins

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

Break down of lactose

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

Phenotype frequencies based on -13910 C/T allele frequency

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

QUESTIONS?