Multifactorial diseases

Question 1

What are multifactorial diseases?

Answer 1

Complex disorders.

• many genetic and environmental factors
• non-Mendelian inheritance

Question 2

What is the difference between polygenic and multifactorial?

Answer 2

POLYGENIC - multiple genes

MULTIFACTORIAL - multiple factors, both genetic and environmental

Question 3

What does familial clustering mean?

Answer 3

Occurring more in a family than would be expected by chance.

-still environmental

Question 4

What does the statistic (lambda)s show?

Answer 4

The relative risk to 2nd sibling compared to general population.
-familial disease

Question 5

Is schizophrenia inherited?

Answer 5

Familial; inherited but not Mendelian.

-closer relation&raquo_space; higher risk

Question 6

What is the relative risk to siblings and identical twins of schizophrenia?

Answer 6

Siblings - 9%.

Identical twins - 48%.

Question 7

What sort of disease are cluster headaches?

Answer 7

Multifactorial.

-run in families

Question 8

What is a major environmental factor for twins?

Answer 8

The uterus (pregnancy).

Question 9

If multifactorial diseases have a genetic component, should there be a higher concordance in monozygotic (MZ) or dizygotic (DZ) twins?

Answer 9

Higher concordance in monozygotic (MZ) twins.

-MZ twins = identical

Question 10

Do twins share the same placenta?

Answer 10

• Monozygotic twins share the same placenta.

- Dizygotic twins either share the same placenta, or have separate placentas.

Question 11

Do MZ have the same environmental exposure before birth?

Answer 11

MZ twins share placenta, but not necessarily same environment (»different birth weights).
-still environmental influences

Question 12

How can adoption studies be used to determine the genetic influences of conditions?

Answer 12

Child shares environment but different genetics to adoptive parents.
-ethical issues though

Question 13

What type of inheritance is shown by genes in polygenic / multifactorial inheritance?

Answer 13

ADDITIVE.

• not dominant / recessive
• phenotypes determined by many genes

Question 14

What is usually the distribution of polgenic / multifactorial genes in the general population?

Answer 14

Tend to be normally-distributed.

-Gaussian curve

Question 15

Give some examples of disorders that show multifactorial inheritance.

Answer 15

CONGENITAL - cleft lip, neural tube defects, heart defects

ACQUIRED - asthma, cancer, diabetes (type 2), IBD

Question 16

What is the purpose of genetic association studies?

Answer 16

To relate DNA variation with a disease / trait.

-estimates population risk and phenotype susceptibility

Question 17

What are in the 2 groups for association studies?

Answer 17

One group of affected individuals, one control group representing normal population (some affected individuals).

Question 18

Which type of inheritance is usually more common; multifactorial or Mendelian?

Answer 18

Multifactorial inheritance is normally more common than Mendelian, but less severe.

Question 19

What are single nucleotide polymorphisms (SNPs)?

Answer 19

Variation in a single nucleotide at a specific position in the genome.

Question 20

How common are single nucleotide polymorphisms?

Answer 20

Very common.

• everyone has many
• usually no effect

Question 21

What are used to detect single nucleotide polymorphisms?

Answer 21

SNP chips.

-‘light up’ means a base is present

Question 22

What is linkage disequilibrium?

Answer 22

The occurrence of combinations of linked genes in non-random proportions.
-DNA surrounding mutation is often similar

Question 23

What sort of graph is show linkage disequilibrium?

Answer 23

Manhattan plot.

-scatter graph

Question 24

What is the thrifty phenotype hypothesis?

Answer 24

States that reduced fetal growth is strongly associated with a number of chronic conditions later in life.
-initially involved maternal malnutrition and metabolic syndrome

Question 25

What is the pathology of Alzheimer’s?

Answer 25

• Shrinkage of brain

- Beta-amyloid protein accumulation in nerves

Question 26

Is Alzheimer’s inherited?

Answer 26

Inherit susceptibility, not condition itself.

-environmental factors too

Question 27

Familial clustering; what is the sibling relative risk in Alzheimer’s?

Answer 27

3-10.

Question 28

What is the inheritance of early onset Alzheimer’s thought to be?

Answer 28

Genetically heterogenous.

• different genes involved
• e.g. PSEN1, PSEN2&raquo_space; cleave amyloid precursor
• e.g. amyloid precursor mutation

Question 29

What gene has an effect on the age of onset of Alzheimer’s?

Answer 29

Apo-lipoprotein E (APOE).

Question 30

Which haplotype of APOE increases the susceptibility of Alzheimer’s, and which has a protective effect?

Answer 30

APOE*E4 - increased susceptibility.

APOE*E2 - protective effect.

Question 31

What is deposited in age-related macular degeneration?

Answer 31

Drusen.

-early deposition = main risk factor

Question 32

What is the simplest “multifactorial” genetic condition?

Answer 32

Ageing macular dystrophy.

-smoking/light exposure and genetic defect&raquo_space; 70x increased risk

Question 33

What are the genetic and environmental causes of ageing macular dystrophy?

Answer 33

GENETIC - CFH, ARMS2

ENVIRONMENT - smoking, light exposure

Question 34

What is the purpose of screening in multifactorial diseases?

Answer 34

Identifies individuals at increased risk.

• does not confirm disease
• e,g. BRCA