Multifactorial inheritance

Question 1

Variation

Answer 1

Changes in the genome can lead to altered effects of a protein or control of genes. How variation affects health depends on what type and where it is. It may simply be responsible for normal variation, cause disease directly, or modulate disease susceptibility or resistance to environmental triggers.

Question 2

Mendelian inheritance

Answer 2

Caused by mutation in a single nuclear gene, following classic inheritance patterns (dominant/recessive, autosomal/X-linked).

Question 3

Non-mendelian inheritance

Answer 3

Relies on multiple genes (polygenic) and environmental factors. May be multifactorial, especially in common complex disorders.

Question 4

Common conditions

Answer 4

• coronary artery disease
• diabetes mellitus
• cerebrovascular disease
• schizophrenia
• breast and bowel cancers
• some congenital anomalies

Question 5

Studies of disease factors

Answer 5

The genetic and environmental factors that contribute to disease can be identified by observational studies in different groups of people, such as:

• familial clustering
• twin studies (monozygotic/dizygotic)
• adoption studies
• population and migration studies

Question 6

Polygenic inheritance

Answer 6

Multiple genetic factors each only make a small contribution to the final phenotype, resulting in a normal distribution of continuous traits in the population.

Question 7

Liability threshold

Answer 7

Above the liability threshold, an individual will develop a multifactorial condition. Bell-shaped liability curves can be drawn for whole populations, or families, who are likely to share environmental factors as well as genetics.

Question 8

Empiric risk

Answer 8

The chance that a disease will occur in a family, based on experience with the diagnosis, past history, and medical records rather than theory.

Question 9

Association studies

Answer 9

Aim to identify the genetic factors for common conditions by looking for shared DNA patterns in patients with the same condition.

Question 10

Genome wide association study (GWAS)

Answer 10

Looking for single-nucleotide polymorphisms (SNPs) at a particular location, comparing the genomes of thousands of people with and without the condition.

Question 11

Genomics

Answer 11

The study of all the genes and non-coding regions of DNA, including genetic mapping and DNA sequencing. It will become increasing useful for:

• informing clinical practice
• developing new targeted therapies
• influencing health decisions
• identifying genetic risk

Question 12

100,000 genomes project

Answer 12

A government project in which the whole genomes of 100,000 NHS patients were sequenced. One of the aims was to improve diagnosis and treatment for rare inherited diseases and some common cancers.