Coeliacs

Question 1

Concordance rates in twins and siblings

Answer 1

80% twins (greco)
10% siblings (macdonald)
1% population

Question 2

HLA genes

Answer 2

Chr 6
DQ2 - 90% N europeans
DQ8 - 5% CD 10% pop
DQ2.5 - 90% N europeans 20% non CD controls, strong CD association

Protein variants bind to gluten peptides and provide more reinforced presentation to immune system

Question 3

Non HLA methods

Answer 3

GWLS- identifies chr regions likely to contain disease causing genes
Eg in twins

Candidate gene analysis- focus on gene that may be involved and study in cohort of cases and controls

GWAS- observational study of genome wide set of genetic variants in cases and controls. Identify SNPs

Question 4

Non HLA genes

Answer 4

2Q33 - antigen processing, tolerance, immune activation. T cell activation. CTLA4 + CD28 = t cell actuvation

MICA5.1 - NK/CD8 cell binding

19Q13.1 - increased CD risk

Many more genes associated with adaptive immune activation and inflammation