Complex Genetic Disorders

Question 1

why is fat needed for health?

Answer 1

• 25% - 30 % fat is normal for middle aged woman - fat is needed for storage of food - insulation - source of hormones

Question 2

what happens when one does not have enough fat ?

Answer 2

• infertility - miscarriage - death from infection - osteoporosis

Question 3

what is the heritability of obesity?

Answer 3

• 0.77 This means 77% of the variation between individuals in a given environment is genetic

Question 4

what is the BMI measurement of obesity?

Answer 4

BMI>30 morbid obesity BMI>40 BMI is the ratio of weight to height squared

Question 5

what are the causes of obesity? controlled by genes

Answer 5

• behaviour ( feeding and physical activity) - physiology (resting metabolism and energy expenditure)

Question 6

What are the three types of obesity?

Answer 6

Syndromic, Monogenic and Common

Question 7

What is syndromic obesity commonly accompanied by?

Answer 7

Mental Retardation Dysmorphic features Prader Willi is the most common form

Question 8

describe monogenic obesity:

Answer 8

• dominant or recessive single gene disorders - leptin was the first obese gene to be identified

Question 9

how did scientists find out about leptin?

Answer 9

• there are circulatory systems of two mice, one lean and one obese connected - the obese mouse stopped eating and had reduced blood sugar - there was a transfer of blood borne lectin

Question 10

Describe the action of leptin.

Answer 10

Leptin is hormone produced by adipocytes and travels to the brain to let the brain know how much fat is stored in the adipose cells and thus regulates feeding - More fat means more lectin so it tells your brain you don’t need to eat anymore - lectin also stimulates puberty - before puberty there is a build up of fat which sends permissive signal via leptin to the brain

Question 11

why are some people not responsive to leptin?

Answer 11

• fat people have an insensitivity to leptin - the leptin receptor in the brain is deficient - some people have a genetic deficiency of the leptin receptor

Question 12

What are some features of leptin deficiency?

Answer 12

• Low thyroid function - Immune problems - Incomplete/lack of puberty so infertile - uncontrollable appetite - leptin deficiency is very rare

Question 13

What is the treatment for leptin deficiency?

Answer 13

Recombinant leptin

Question 14

what controls body fat levels?

Answer 14

• The leptin-melanocortin adipostat regulates body fat levels.

Question 15

Name some genes that cause monogenic obesity.

Answer 15

MRAP2 - recessive POMC PCSK1 MC4R - dominant and most common

Question 16

What are Genome Wide Association Studies used for in relation to obesity?

Answer 16

• look at a persons genome and compare with a non obese person to identify natural variations and see if there are markers more common in one group - the method is hypothesis free - the process is not looking at mutations only at sequence variations - FTO is a big marker GWAS-identified single nucleotide polymorphisms explain only a small proportion of common obesity risk

Question 17

what genetic factors might cause common obesity?

Answer 17

• Patients with syndromic forms of obesity have more Genomic Structural Variations

Question 18

what do genomic structural variations include?

Answer 18

• Copy-Number Variation (CNVs) - deletions - extra copies of certain regions - inversions and translocations

Question 19

what does a deletion at 16p11.2 cause?

Answer 19

-Onset of obesity at 8-10 years - Explains 1% of adult morbid obesity - risk of autism - Duplication carriers are more likely to be underweight