Genetics of the Immune system

Question 1

What is a genetic marker?

Answer 1

a DNA sequence with a known location and is easily identifiable

Question 2

What are the features of an ideal marker?

Answer 2

highly polymrophic; randomly distribtued; easily asasyable; stability (no change through generations)

Question 3

What is the function of genetic markers?

Answer 3

closely associated with gene of interest and allows you to look at inheritance

Question 4

What are the ways of determining the genetic component of a disease?

Answer 4

adoption studies; immigration studies; family studies; twin studies

Question 5

What is the equation for family studies?

Answer 5

risk to siblings of patients/population prevalence

Question 6

What are epigenetic mechanisms?

Answer 6

environmental factors may impact on DNA modifications and thus immune phenotype and disease susceptibility

Question 7

What is GWAS?

Answer 7

genome wide association studies

Question 8

Is sharing of immune phenotype marked in MZ twins?

Answer 8

no

Question 9

Which genes tend to have the strongest association with AI disease?

Answer 9

HLA genes

Question 10

Why do HLA genes have teh strongest association with AI disease?

Answer 10

human immune response genes regulating presenation of antigen to T cells

Question 11

What is the function of MHC polymorphism?

Answer 11

allows a better ability to raise an immune response across a population

Question 12

Which chromosome is the TCRa locus found on?

Answer 12

14

Question 13

How many Va gene segments are found in the TCRa locus?

Answer 13

70-80

Question 14

Which chromosome is TCRb locus ?

Answer 14

7

Question 15

What is the difference between the organisation of TCRa and TCRb loci?

Answer 15

TCRa has v segments followed by J segments followed by a single C gene wherease TCRb has V segments then 2 separate clusters each containing a single D with 6/7 J and a single C gene

Question 16

What is found between the V and J gene segments of the TCRa locus?

Answer 16

TCRd locus

Question 17

What is the significance of some parts of hte genome being linked to multiple AI diseases?

Answer 17

immune dysregulation involved in very different diseases shares common pathways

Question 18

What is allelicc discondancy?

Answer 18

alleles have opposite effects on the risks of different diseases

Question 19

Waht is allelic heterogeneity?

Answer 19

different polymorphisms in the same region are associated with different diseases

Question 20

Why are IL-23R polymorphisms common across immune mediated diseases?

Answer 20

IL-23R is important in DCpolarisation of T cells into Th17

Question 21

What is GWAS?

Answer 21

a method taht leverages the information from genetic variants spread through teh whole genome and compares allel frequencies between a group of patients and a group of healthy controls- if statistically signif, allele is disease associated

Question 22

Which diseases a re linked to a locus encoding genes for receptors that contorl T cell activation CD28; ICOS and CTLA4?

Answer 22

coeliac; RA and T1DM

Question 23

when are genes linked?

Answer 23

located on the same chromosome

Question 24

What is genetic syequilibrium?

Answer 24

certain alleles of each gene are inherited together more often than would be expected by chance- can be due to actual gene linkage or form of functional interaction where some combinations of alleles at the 2 loci affect the viability of potential offspring

Question 25

Why can linking associated SNPs to their effector genes be difficult?

Answer 25

causal variants may not necessarily affect the cloest genes but act through long-range genomic interactions

Question 26

What is a quantitative trait locus?

Answer 26

region of the genome that is correlated with a quantitative phenotype

Question 27

Why is Mendelian not synonymous with monogenic defects?

Answer 27

Mendelian implies full penetrance

Question 28

What is expressivity?

Answer 28

variability of the phenotype considered among the patients studied who carry a given genotype