Flashcards in Genetics of the Immune system Deck (28)
What is a genetic marker?
a DNA sequence with a known location and is easily identifiable
What are the features of an ideal marker?
highly polymrophic; randomly distribtued; easily asasyable; stability (no change through generations)
What is the function of genetic markers?
closely associated with gene of interest and allows you to look at inheritance
What are the ways of determining the genetic component of a disease?
adoption studies; immigration studies; family studies; twin studies
What is the equation for family studies?
risk to siblings of patients/population prevalence
What are epigenetic mechanisms?
environmental factors may impact on DNA modifications and thus immune phenotype and disease susceptibility
What is GWAS?
genome wide association studies
Is sharing of immune phenotype marked in MZ twins?
Which genes tend to have the strongest association with AI disease?
Why do HLA genes have teh strongest association with AI disease?
human immune response genes regulating presenation of antigen to T cells
What is the function of MHC polymorphism?
allows a better ability to raise an immune response across a population
Which chromosome is the TCRa locus found on?
How many Va gene segments are found in the TCRa locus?
Which chromosome is TCRb locus ?
What is the difference between the organisation of TCRa and TCRb loci?
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
What is found between the V and J gene segments of the TCRa locus?
What is the significance of some parts of hte genome being linked to multiple AI diseases?
immune dysregulation involved in very different diseases shares common pathways
What is allelicc discondancy?
alleles have opposite effects on the risks of different diseases
Waht is allelic heterogeneity?
different polymorphisms in the same region are associated with different diseases
Why are IL-23R polymorphisms common across immune mediated diseases?
IL-23R is important in DCpolarisation of T cells into Th17
What is GWAS?
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
Which diseases a re linked to a locus encoding genes for receptors that contorl T cell activation CD28; ICOS and CTLA4?
coeliac; RA and T1DM
when are genes linked?
located on the same chromosome
What is genetic syequilibrium?
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
Why can linking associated SNPs to their effector genes be difficult?
causal variants may not necessarily affect the cloest genes but act through long-range genomic interactions
What is a quantitative trait locus?
region of the genome that is correlated with a quantitative phenotype
Why is Mendelian not synonymous with monogenic defects?
Mendelian implies full penetrance