Lecture 27- Principles of Multifactorial Disease

Question 1

Multifactorial Disease

Answer 1

Multifactorial disease are complex, non-mendelian disorders that occur in families (more then chance alone.), but don’t have a clear pattern of inheritance.

This is because there are many factors (genetic AND envirnmental) that contribute to the phenotype of disease.
There is now more info on common alleles that have small/moderate effects seperately, but combined have a greater effect (polygenic traits).
This can be caused by both susceptability and modifier genes.

Question 2

Difference between multifactorial to other disorders

Answer 2

Multifactorial involves a combo of both genetic predisposition AND environmental factors. Whereas
‘Monogenic disease’ = all genetic

Environmental Factors

Question 3

Some examples of multifactorial genes

Answer 3

Among the most common encountered in practice

Autoimmune disorders
Parkinsons
hypertension
Alzheimer's
Schizophrenia
diabetes
asthma

Question 4

The Threshold model for a polygenic trait

Answer 4

Assumes ALL individuals have a susceptibility to developing the trait (due to environ + genetic factors), but a THRESHOLD must be reached before its expressed (further along to the right)

This threshold can be lowered/ the curve can shift right due to the accumulation of at risk susceptibility genes.

Question 5

Modifier Genes

Answer 5

NOT SUSCEPTIBILITY GENES.

But once disease susceptibility is present, or the disease has developed, modifier genes can control the severity of the disease phenotypes.

Question 6

Rules for identification of multifactorial disease

Answer 6

• Can be common or rare
• Disorder runs in families with no set pattern
• Higher frequency of disease in 1st degree relatives then 2nd degree, but then decline following is slow due to many susceptibility genes
• Recurrance risk is proportional to # affected family members, severity of condition in the proband

Question 7

Linkage Analysis and multifactorial disease

Answer 7

Can be analysed but are more challenging due to the disease not being caused by a single gene, but instead a combination of genetic polymorphisms resulting in subtle changes of genes.

**Linked genetic markers between 1st degree relatives that prove a genetic locus is linked to phenotype

Question 8

23 & me

Answer 8

A kit you can pay for online, uses your saliva to give you information on you SNPs (not the whole genome, provides ancestry info and disease risk.

Question 9

PMs and disease risk

Answer 9

Some polymorphisms / SNPs have an association with specific diseases. this doesn’t mean if you have that PM you’ll get that disease, it just means you’re at higher RISK

Question 10

Genome-Wide Association Studies

Answer 10

GWAS
Look at common genomic variants in lots of individuals and try determine if it is associated with a specific trait.
Typically looks at associations between SNPs and multifactorial diseases

Question 11

Personalised Medicine

Answer 11

Using an individuals DNA / genetic information to make decisions on how to treat them

Question 12

Precision Medicine

Answer 12

Using a patients health information (genetics, blood-test results, response to medicines) would be accessible to scientists. Lab discoveries inform/impact patient care.

Question 13

Examples of precision/personalised medicine

Answer 13

Prevention
Screening
Diagnosis
Prognosis
Drug efficacy
Drug tolerance

Question 14

Alzheimers Disease

Answer 14

2% AD disorder, but mostly multifactorial (late onset).
MF sufferers due to an accumulation of susceptility genes. eg) ApoE
homozygous = greatest risk
heterozygous= some risk
-Risk increase with amount of 1st degree relative affected.
-Runs in families but no ‘pattern of inheritance

Question 15

Why wouldn’t you reccomend testing for the ApoE Gene in Alzheimers

Answer 15

1) It’s a susceptability gene, so it doesn’t mean they will get disease
2) We have no treatment for alzheimers, no waay to change the risk