Complex gene traits Flashcards
Define genetic predisposition?
An individual has a genetic susceptibility to develop a certain disease, but does not guarantee that the person will develop a disease.
What is a complex disease?
- Caused by a combination of genetic, environmental and lifestyle factors.
- Does not follow the Mendelian pattern of inheritence
Describe how common/ rare complex disease is compared to Mendelian? Is is single gene or polygenic
Complex disease is more common, and polygenic
Mandelian diseases are rarer and single gene
Describe the frequency of genes in the population and the effect on gene function seen in complex vs Mandelian disease?
Common Disease–> Gene frequencies have high frequencies in the population, and a smaller effect on gene function
Mandelian Disease–> Gene frequencies have low frequencies in the population and a larger effect on gene function
Is penetrance higher or lower in Complex gene disease
Higher
Give some examples of complex disease
Alzheimers, hypertension, CHD, epilepsy, T2D
What can you tell by studying the degree of familial clustering?
The risk to a relative or sibling of an affected erson compared to the population risk
Higher value= higher the familial clustering
How do twin studies work?
Assess monozygotic twins vs dizygotic twins
Assess and measure the trait you are studying (eg HTN)
Higher the correlation= higher chance that genetics are involved
What situation is ideal for completing twin studies
Study twins seperated at birth
How would you conduct an adoption study?
Check disease status in biological and adopted family, and test for correlation between family members.
- Similarity to biological parents= genetics
- Similar to adopted parents= home environments
What are the difficulties in adoption studies?
- Obtaining the info
- Selective placement of individuals
Why do scientists want to identify monogenic and complex traits?
- Provide better understanding of aetiology
- Identify molecular targets for developing new treatments
- May help identify at risk individuals
What is linkage analysis in families?
Measuring trait of interest in affected sibling pairs
Why are rare monogenetic diseases difficult to detect?
- Difficult to detect via linkage analysis due to locus heterogeneity
- Only a small number of patients/ family available for study
What does genome wide association studies study?
The whole genome simultaneously
Name 4 genes identified as being involved in HTN
1- Guanylate Cyclase Units
2- Natruiretic peptide receptor 3
3- Adrenomedullin
4- miK- 425
Where is mIR-425 expressed
Atria and ventricles
What % of hypertension is thought to be genes, and what is lifestyle
30-50% genes
50-70% lifestyle
What is the inheritence pattern of glucocorticoids remediate aldosteronism?
Autosomal dominant
What is the inheritance pattern of apparent mineralcorticoid?
Autosomal recessive
What is the inheritance pattern of Gordon’s Syndrome?
Autosomal dominant and recessive
What is the inheritance pattern of Liddle’s Syndrome?
Autosomal dominant
What happens in mIR-425 is inhibited?
Enhances atrial ANP release in response to salt excess in hypertension and heart failure
What is the impact of genetic variant in the NPPA 3’ UTR rn5068
Impacts ability of a miR to target NPPA mRNA
What is the role of SLC39A8
Transports Zn, Cd, Mn
What is rs5068
It encodes ANP and regulates NPPA mRNA
What happens if you increase copy of rs5068 minor G allele?
- Increased plasma ANP levels
- Decreased systolic pressure
- Decreased diastolic pressure
- Reduced odds of hypertension
What is furin
A widely expressed member of subtilisin like proprotein convertase family
What does furin activate
- Receptors (insulin and growth factor)
- Plasma proteins
- Hormones
Genetic risk score of ….. is associated with CV outcomes
29
