15. Genome and environment (wk12)

Question 1

Highly penetrant variations characteristics

Answer 1

• Trait it produces will almost always be apparent in an individual carrying the allele
• The variation significantly influences the function of a gene or its products

Question 2

Low penetrant variations characteristics

Answer 2

• Produces perceptible phenotypes only sometimes
• The variation does not significally influence the gene or its products, or the intact gene is not essential for the normal phenotype
• Effect apparent when interaction w/other variations or environmental factors

Question 3

Highly penetrant variations and the environment examples

Answer 3

1) Xeroderma pigmentosum (gene: DNA repair)
- Environmental factor/phenotype: UV/skin cancer

2) Phenylketonuria (PAH)
- Phenylalanine/mental disorders

3) Familial hypercholesterolemia (LDLR)
- Cholesterol/atherosclerosis

Question 4

Low penetrant variations and the environment examples

Answer 4

1) Alpha 1-AT deficiency
- Mutated SERPINA1 gene - defective prod. alpha 1 AT
- Carriers sensitive to sigarette smoke + other airparticles

2) Factor V Leiden mutation (R506Q)
- Factor V cannot be inactivated by activated prot C
- Oral contraceptives, inactivity, pregnancy increase risk of DVT

Question 5

Traces of microorganism-human genome interactions in the human genome

Answer 5

• Horizontal gene transfer - over 145 human genes originate from bacteria
• 8 % from retroviruses
• Human genes specifically against bacterial/viral infections: TLR, MBL, CD14, NOD2 or APOBC3G, TRIM5, BST2

Question 6

CCR532

Answer 6

• Functionless HIV-R - resistance against HIV
• Only in Caucasians
• Might be so prevalent due to S. Aureus epidemic 7000 yrs ago

Question 7

Major determinants of pigmentation in humans

Answer 7

SLC24A5 gene: A111T
SLC45A2 gene: L374F
Both are fixed in light-skinned Europeans

Question 8

Light-gene interaction today

Answer 8

Melanin: protects from UV, and blocks vit. D (ish)

• Melanoma prevalence increased: more sunbathing
• Vit. D deficiency in black people that have moved north

Question 9

AMY1 gene

Answer 9

Codes for salivary amylase - digests starch

- High starch diet populations had more copies of AMY1

Question 10

High altitude adaptations

Answer 10

• Higher Hb concentrations in Andeans
• Increased RR in Tibetans
• Special EPAS1 version in Tibetans

Question 11

Lactose intolerance

Answer 11

• Lactose intolerance is actually the wild type
• Some human populations have developed lactose persistence (SNP in LCT gene)
• Europeans, Tanzanians, Kenyans and Sudanese - all have different SNP mutations giving them lactose persistence

Question 12

Convergent evolution

Answer 12

Different processes in different population lead to similar phenotypes

Question 13

Smoking-genome interactions

Answer 13

• Heritability: 60 %
• D2 dopamine R gene A1 allele is associated with stress-induced cigarette craving
• SLC6A3 (dopamine transporter gene) associated with stress-induced craving

Question 14

Nicotine pathway

Answer 14

CYP2A gene: codes for nicotine-degrading enzyme

- Deficient in 10-17 % - reduced possibility of addiction

Question 15

Smoking and life expectancy

Answer 15

C4B*Q0: inactive variant

• Very much less seen in elderly
• Associated strongly with smoking

Arg16: increased risk of asthma in smokers

Question 16

CYP1A1

Answer 16

Degrades toxins in sigarette smoke

• Children of smokers have increased risk of ALL
• Esp. with certain haplotypes of CYP1A1 in the child and heavy smoking of parents at home

Question 17

CD14

Answer 17

Part of innate immunity - codes for LPS-R with a ligand found on surface of G- bacteria

• TLR4
• CD14 promoter polymorphism (-159C/T) - T/T genotype reduced risk of atopy and rhinitis in Russians, but higher risk in Finland
• Exposure to farming environment reduces risk of nasal allergies