obesity genomics Flashcards
how to quantify the extent to which a trait is genetic and environmental?
- the use of monozygotic and dizygotic twins suggest BMI is heritable
- twin studies suggest at a given time within a given population, 50% of variation in BMI is due to genetic variation - distant relatedness is correlated with BMI and suggest 30% of variation in BMI is genetic
- siblings sharing 60% of their genome have more similar BMI than siblings sharing 40% of their genome
changes in which AA leads to obesity?
- the AA position (codon) change in gene 203 results in the mutation, the arginine gets mutated to histamine resulting in obesity
recessive diseases are common in which cases?
in consanguineous (blood related people) marriages
mutations in which gene encoding for important proteins causes obesity? and where are the genes found?
mutations in
- POMC - propiomelanocortin
- MC4R - melanocortin 4 receptor
- leptin - the mutations in leptin resulted in reduce/absence of leptin which leads to obesity
- LEPR - leptin receptor
- all of these are found in the arcuate nucleus of hypothalamus
what are the characters of prader willi syndrome?
- short stature
- hypotonia (poor muscle tone)
- small hands and feet
- obesity: hyperplasia
- mild-moderate retardation
- 1/15000
what causes the Prader will syndrome?
it is caused by defeat in an imprinted gene
- usually, it needs only one copy of gene to be normal
- under normal conditions the paternal copy is active and maternal copy fo gene is switched off due to methylation in the egg
- however, disease occurs when something goes wrong with paternal copy (e.g. deleted)
- we only need the paternal copy of the prader willi gene
genetic variants are more frequently present in cases than controls
A. True
B. False
A. True, the variants provide the probability of disease status
what is the role of GWAS in obesity?
- GWAS found 97 regions of the human genome associated with BMI
- individually rare but collectively account for 10% of severe obesity in children
what is the role of common genetic variants?
common genetic variants hit loci containing monogenic obesity genes, mutations in which affect appetite
e.g. POMC, MC4R, BDNF and SH2B1
in which region of the body were the obesity mutated genes identified by GWAS?
they are more likely to be expressed in CNS including hippocampus, hypothalamus and limbic system
what is leptin story?
- the mice lacking could not stop eating and when leptin was induced they came back to their normal weight
- after treatment with leptin reduced their appetite thus reducing obesity
however, it does not work for leptin receptor because the mutation is in the receptor and not gene
what is the genetic composition of obesity?
monogenic and rare mendelian form
what are the potential effects of maternal obesity on birth weight and health of offspring?
- Genetically elevated maternal BMI and BGL were potentially casually associated with higher offspring birthweight, sugar goes through placenta
- Genetically elevated maternal SBP was potentially casually related to lower birth weight
what is the role of BMI in depression and psoriasis ?
- higher BMI is associated with higher odds of depression and
- higher BMI increases the risk of psoriasis
how genetics can influence type of food intake and not just over all food intake
- FGF2 - associated with higher carbohydrate intake
2. FTO - associated with obesity of higher protein diet