This document discusses genetics and evolution of lactose tolerance/intolerance. It covers what lactose intolerance is, its causes like primary and secondary lactase deficiency, symptoms, diagnosis methods, the role of the LCT gene and lactase enzyme, how lactose is broken down, and mutations involved in lactose persistence. It proposes two hypotheses for the evolution of lactose tolerance - genetic drift and culture/selection - and notes the condition is most common in Northern European populations where lactose persistence arose between 3000 BC to AD 1200.

1. 
Genetics and
Evolution of lactose
(in)tolerance
By:Tracy Adkins

2. 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

3. What is lactose intolerance
 The inability or
insufficient
ability to digest
lactose
 Body can’t
produce lactase

4. 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

5. 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

6. Diagnosis
 Hydrogen BreathTest
 High levels of Hydrogen if lactose is undigested
 Stool AcidityTest
 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

7. 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

8.  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

9. 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

10. Break down of lactose

11. 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

14. 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

15. 2 hypothesis
 Genetic drift
 Culture-historical/ selection
 Genetic pressures
 Easily stored
 Milk as a source of water
 Increased calcium absorption
 Rickets and osteomalacia

17. 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

18. Phenotype frequencies based on -13910 C/T allele
frequency

19. LP phenotype frequencies based on frequency data for the currently
known LP associated allelic variants, excluding the -13,910 C>T allele

20. 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

21. 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 andAsian
populations are affected.
 Compared to other mammalian
species, human milk has the highest
concentration of the disaccharide
lactose