Lecture 24: Principles of Multifactorial disease Flashcards
What is a multifactorial diseases
Non mendelian disorders that occur in families more frequently than permitted by chance alone, but shows no clear classical pattern of inheritance. This may come from genes which predispose towards disease and therefore modify the course of disease process, when presented with different environmental factors.
What are examples of multifactorial diseases
Coronary artery disease, parkinsons, autoimmune disorders, alzheimers, schizophrenia
What are examples of multifactorial diseases
Coronary artery disease, parkinsons, autoimmune disorders, alzheimers, schizophrenia
What is the Pathology of multifactorial inheritance
An inheritance of common alleles that have small/moderate effect individually but when combined have greater phenotypic impact (polygenic trait).
What is the Pathology of multifactorial inheritance
An inheritance of common alleles that have small/moderate effect individually but when combined have greater phenotypic impact (polygenic trait).
- modifier genes for the severity of the disorder,
- the gene and epigenetic factors
- the gene and environmental factors
What are modifier genes
Genes not associated with the disease origin, but once disease susceptibility is present or the disease has developed these genes modify the severity of the phenotype
What is the threshold model for polygenic trait
This model assumes that while all individuals are susceptible to the disease, there is there is a threshold to reach before the disease is expressed. In families where the trait has been demonstrated and when there is more than one individual demonstrating, the normal distribution curve shifts to the right (more of the population with family history above threshold).
How can you identify a multifactorial threshold trait
- Diseases can be common, running in the families but no clear mendelian inheritance.
- Frequency of disease is less in 2nd gen relatives compared to 1st but declines less rapidly than expected
- more family members already affected increases recurrence risk
- the severity of the condition in the proband increases recurrence risk
What does linkage analysis help identify
It looks for co transmission of disease with polymorphisms of possible linked genetic markers.
This tries to link a genetic locus with the phenotype, and is best tested for in 1st degree relatives
What is the challenge for identifying multifactorial disease with linkage
Their causation is a combination of genetic polymorphisms so can have many locuses with subtle contribution to phenotype
What do Genome wide association studies focus on
They examine many common genetic variants to see if they are associated with a trait.
They focus on SNPs and multifactorial diseases
Why is gene identification important for now and the future
- understanding of disease pathophysiology and study around gene environment interactions
-tool for risk prediction which allow disease preventive strategies
Future
-Develop biological assays to monitor disease progression
-identification of new drug targets
What is Personalised medicine
The utilisation of individual genetic information and DNA based technologies to make decisions aimed at maintaining health, preventing disease or improving outcomes of disease
What is precision medicine
The creation of dynamic infrastructure where patients health information in databases accessible to scientists whose discoveries inform patient care
What are some benefits to personalised/precision medicine
- Prevention through lifestyle intervention
- Screening for high risk individuals- early diagnosis
- Presymptomatic diagnosis, non invasive
- Prognosis
- Drug efficacy informed
- Drug tolerance
