CPPS403 - IdentifyingDiseaseGenes II - 10 - Copy Flashcards
(34 cards)
What type of information does GWAS provide?
GWAS tests thousands of variants to find SNPs associated with specific traits or diseases.
GWAS relies on linkage disequilibrium (LD) between observed SNPs and unknown causal variants.
What is linkage disequilibrium (LD)?
The non-random association of alleles at different sites; closer regions have a higher likelihood of being inherited together.
LD is often formed by discrete haplotype blocks with low recombination frequencies.
What does highly polygenic mean in the context of complex traits?
Complex traits are influenced by many loci contributing to their expression.
This implies that multiple genetic variations can affect a single trait.
What is a polygenic risk score (PRS)?
A genetic predictor for disease estimated from GWAS data.
PRS aggregates the effects of many SNPs into a single score.
How do GWAS variants typically relate to gene regulation?
GWAS hits are usually in non-coding regions and require further analysis to identify their target genes.
This includes assessing regulatory elements and their accessibility in relevant cell types.
What is an expression quantitative trait locus (eQTL)?
A genetic locus associated with gene expression changes.
eQTL mapping can indicate whether a SNP is linked to a gene.
What are cis-eQTLs?
Proximal eQTLs, where SNPs are usually within 1 Mb of the gene.
They influence gene expression by being in close proximity to the target gene.
What are trans-eQTLs?
Distant eQTLs, where SNPs are located more than 5 Mb away from the gene or on another chromosome.
They can regulate gene expression remotely.
What do chromosome conformation capture techniques study?
They map chromatin interactions to detect loops and compartments influencing gene regulation.
This method helps identify topologically associating domains (TADs).
What is the significance of topologically associating domains (TADs)?
They represent regions in the genome where interactions between loci are more frequent, impacting gene regulation.
TADs help in understanding the 3D architecture of the genome.
What are some challenges of pharmacogenomics (PGx) GWAS?
They are limited in scope and reproducibility across different genetic ancestries.
Most studies focus on drug responses, toxicities, or adverse drug events.
How do genetic variants in CYP2C19 influence drug therapy?
They guide drug choice and dosage based on a patient’s response to clopidogrel.
CYP2C19 is polymorphic, with alleles categorized as normal, decreased, or increased function.
What is the function of CYP2C19 in drug metabolism?
It catalyzes the bioactivation of the antiplatelet prodrug clopidogrel.
Clopidogrel is used to reduce the risk of myocardial infarction and stroke.
What is the clinical relevance of identifying alleles in CYP2C19?
They can predict a person’s outcome and risk for adverse reactions to clopidogrel.
This information is critical for personalized medicine approaches.
What is the relationship between GWAS and experimental validation?
GWAS can identify loci that, when validated, reveal underlying biological mechanisms.
This is essential for translating findings into clinical applications.
Fill in the blank: GWAS rely on _______ between observed genotyped DNA SNPs and unknown causal variants.
linkage disequilibrium
What is atrial fibrillation (AF)?
A complex disease
What methods are used to identify disease genes associated with AF?
- Enhancer mapping
- Functional validation
- Target sequencing of genes at GWAS loci
- Family studies and linkage analysis
- Candidate gene sequencing
- Genome-wide association studies (GWAS)
What was the first identified mutation related to AF?
KCNQ1
What pattern of inheritance is associated with variants causing AF in families?
Autosomal dominant pattern of inheritance
What significant findings were made between 2006-2017 regarding genes associated with AF?
Loci identified
What significant findings were made in 2018 regarding genes associated with AF?
Loci identified
What is the nearest gene to the 4q25 locus?
PITX2
What was the first GWAS published for AF, and what was the sample size?
Published in 2007 with 550 patients and 4,476 controls
