Principles to multifactoral genetic diseases

Question 1

What are mulitfactoral genetic diseases

Answer 1

Multifactorial (complex) diseases are non-Mendelian disorders
that occur in families more frequently than permitted by
chance alone, but show no clear classical pattern of
inheritance

Question 2

Examples of multifactoral diseases

Answer 2

coronary artery disease autoimmune disorders
congestive heart failure Parkinson’s disease
hypertension
Alzheimer’s disease
stroke
schizophrenia

Question 3

3 main polygenic Risk Factors in
Disease

Answer 3

1. Genetic suspectiability
2. Infectious disease
   3.Immune response

Question 4

What are modifier genes and example

Answer 4

Not associated with the disease origin, but once
disease susceptibility is present or the disease has
developed, these genes modify the severity of
disease phenotype

e.g. the melanocortin-1 receptor gene is
a modifier gene for melanoma

Question 5

Features of multifactorial /
polygenic disorders
-reoccurance risk based on

Answer 5

Disorder runs in families, but no distinctive pattern of
inheritance

Recurrence risk is proportional to number of family members
already affected AND Recurrence risk is proportional to the severity of the condition
in the proband (reflects concentration of adverse alleles)

Question 6

What is linkage

Answer 6

Linkage analysis looks for co-transmission of
disease with polymorphisms of possible linked
genetic markers

When a disease affects 1st degree relatives
(siblings, parent, child), genetic analysis can be
performed to determine whether a genetic locus
can be linked to the phenotype

Question 7

Why is linkage anaylsis not really used in multifactoral diseases?

Answer 7

Multifactorial diseases can also be analysed for linkage but it is more challenging because of causation generally by a combination of genetic polymorphisms resulting in subtle changes in gene interactions/gene expression levels

Affected siblings are likely to share chromosomal regions that
carry a disease-related locus, therefore analysis is often
directed at multiple sibling pairs

Question 8

What is Genome-Wide Association
Studies (GWAS)

Answer 8

Examine many common genetic variants in
different individuals to see if any variant is
associated with a trait

Question 9

Personalised vs Precision
Medicine

Answer 9

Personalised Medicine
 refers to the utilisation of individual genetic information and DNA-based technologies to make decisions aimed at maintaining health, preventing disease or improving outcomes of disease

Precision medicine
 involves the creation of a dynamic infrastructure where patients’ health information (including genetics, blood test results, responses to medications and reactions to therapies) would be accessible to scientists – and where discoveries made in the laboratory could inform patient care

Question 10

Examples of Personalised / Precision Medicine methods

Answer 10

 Prevention: identify those at greatest risk of disease from ‘adverse lifestyle’ e.g. smoking, high alcohol intake, obesity, sun exposure

 Screening: identify high risk individuals for prioritised screening
e.g. earlier age, more frequent, greater sensitivity

 Diagnosis: pre-symptomatic diagnosis; DNA-based tests that provide diagnosis before other (often invasive) studies

 Prognosis: identify disease process that may be aggressive and require
alternative therapeutic approach

 Drug efficacy: identify patients who will receive greatest benefit from a
particular drug (avoiding ‘try and see’ approach)

 Drug tolerance: identify patients likely to experience drug side-effects, who would benefit from either a lower dose of the drug or an alternative agent