Complex Genetic Diseases Flashcards
What is monogenic diabetes?
single gene defect and can develop at any point in life
Give examples of monogenic diabetes
MODY, permanent neonatal diabetes, mitochondrial diabetes
Give characteristics of MODY
autosomal dominant
affects gene involved in beta cell glucose sensing and insulin secretion
treatment depends on gene
What is polygenic diabetes?
compilation of genetic changes that increase predisposition to developing type1/2 diabetes
always a second hit due to environment
Why are genes studied in diabetes?
investigate pathophysiology
define and predict risk
identify monogenic causes
determine in genotype influences treatment choices/outcomes
What is heritability?
study of genetic contribution to increased risk of disease
Why is heritability difficult to study?
many factors that are both genetic and non0genetic are difficult to separate
How is heritability studied?
study monozygotic and dizygotic twins, first and second degree relative
How is GWAS used in diabetes?
see if diabetes is associated with SNPs to increase understanding
What has been found in GWAS for T2 diabetes?
90 loci, effect size is small, SNPs account for 6% of T2 diabetes, SNPs affect beta cell function
How is GWAS information used?
produce genetic risk scores and personalise treatment
What are genomic copy number variants?
deletions, duplications and insertions present in the genome
What do CNVs do?
increase risk of polygenic disease
What are the implications of diagnosing monogenic diabetes?
incomplete understanding regarding benefits of diagnosis
interpreting variants with unknown significance
confusion between type 1/2
