The Genetics of Diabetes

Question 0

to what class of diabetes does MODY belong?

Answer 0

the “other specific subtypes” class of diabetes

Question 1

what is MODY?

Answer 1

maturity onset diabetes of the young

Question 2

MODY is a complex disease: true or false?

Answer 2

false - MODY is a Mendelian disease

Question 3

MODY has no know pattern of inheritance: true or false?

Answer 3

false - MODY is a Mendelian disease with a known autosomal dominant pattern of inheritance

Question 4

could MODY be considered a “simple” Mendelian disease?

Answer 4

no, as the disease shows GENETIC and CLINICAL heterogeneity

Question 5

variations in which genes are known to cause which subtypes of MODY?

Answer 5

MODY 1 = HNF-4a
MODY 2 = glucokinase
MODY 3 = HNF-1a
MODY 4 = IPF-1
MODY 5 = HNF-1B

Question 6

what is glucokinase?

Answer 6

an enzyme within the pancreatic beta cell

Question 7

what is the function of glucokinase?

Answer 7

to phosphorylate glucose within pancreatic-B cells and induce insulin release via ATP inhibition of the K+ATP channel

Question 8

what mutation in the glucokinase gene results in MODY 2?

Answer 8

N254H mutation

Question 9

how is insulin affected in type II diabetes?

Answer 9

⬇️ insulin secretion and ⬆️ insulin resistance

Question 10

type II diabetes is a Mendelian disease and shows an autosomal dominant pattern of inheritance: true or false?

Answer 10

false - type II diabetes is a complex disease with no known pattern of inheritance

Question 11

in type II diabetes, is concordance higher in monozygotic or dizygotic twins? what does this mean?

Answer 11

monozygotic twins - this means that there is a significant genetic component to type II diabetes

Question 12

what is the estimated sibling risk ratio for type II diabetes?

Answer 12

3

Question 13

what are three risk alleles for type II diabetes?

Answer 13

KCNJ11 - E23K variant
PPARG - Pro12Ala variant
TCF7L2 variants

Question 14

what does the KCNJ11 gene encode?

Answer 14

a protein component of the potassium-ATP channel

Question 15

what is the effect of the E23K risk allele in type II diabetes?

Answer 15

increases susceptibility to type II diabetes with an odds ratio of 1.2

Question 16

the E23K variant of the KCNJ11 gene is found in only a small proportion of the population: true of false?

Answer 16

false - the E23K variant is carried by 40% of the population

Question 17

what is PPAR-y?

Answer 17

a transcription factor

Question 18

what molecule does PPAR-y often dimerise with in order to activate genes involved in glucose and fat metabolism?

Answer 18

RXR (retanoic acid)

Question 19

which variant in the Pro12Ala allele for type II diabetes is associated with increased susceptibility to type II diabetes?

Answer 19

the Pro variant, with an odds ratio of 1.2

Question 20

the Pro variant of the Pro12Ala allele, associated with type II diabetes, is present in less than half of the population: true or false?

Answer 20

false - the Pro variant is present in 80% of the population

Question 21

in type II diabetes, the number of risk alleles present in an individual has no effect on susceptibility to disease: true or false?

Answer 21

false - it has been found that ⬆️ coined of risk alleles = ⬆️ risk of diabetes

Question 22

what does the gene TCF7L2 encode?

Answer 22

a transcription factor

Question 23

what susceptibility alleles did the type 1 diabetes genetics consortium (T1DGC) identify?

Answer 23

over 40 non-HLA risk alleles, including IL10, CTRB1 and GAB3

Question 24

what susceptibility alleles for TIID did the WTCCC identify?

Answer 24

already known: KCNJ11, PPARY and TCF7L2

novel: CDKN2A/2B, FTO