Multifactorial Complex Disorders

Question 1

Which inheritance patterns are ‘classical’ / Mendelian?

Answer 1

• Dominant/recessive.

- Autosomal/X-linked.

Question 2

Which inheritance patterns are non-Mendelian?

Answer 2

• Multifactorial inheritance patterns.

- Maternal (mitochondrial) inheritance patterns.

Question 3

What is familial clustering?

Answer 3

Where the incidence of a disorder in a family is different from the incidence in the general population (such that it is clustered in the family).

Question 4

What might be the objective of a twin study in gathering evidence for genetic factors in complex diseases?

Answer 4

To investigate the incidence in monozygotic compared with dizygotic twins.

Question 5

What might be the objective of an adoption study in gathering evidence for genetic factors in complex diseases?

Answer 5

To investigate the incidence in adopted children of the disorders which their biological parents had.

Question 6

What might be the objective of a population and migration study in gathering evidence for genetic factors in complex diseases?

Answer 6

To investigate the incidence in people from a particular ancestry group when they move to a different geographical area.

Question 7

List 6 common complex diseases (with multifactorial inheritance) that are congenital.

Answer 7

1 - Cleft lip.

2 - Congenital dislocation of the hip.

3 - Congenital heart defects.

4 - Neural tube defects.

5 - Pyloric stenosis.

6 - Talipes.

Question 8

List 7 common complex diseases (with multifactorial inheritance) that are adult onset disorders.

Answer 8

1 - Diabetes mellitus.

2 - Epilepsy.

3 - Glaucoma.

4 - Hypertension.

5 - Coronary artery disease.

6 - Manic depression.

7 - Schizophrenia.

Question 9

Which gene is (partially) responsible for the development of neural tube defects?

Answer 9

The MTHFR gene.

Question 10

What is empiric risk?

Answer 10

• The probability that a disease will occur in a family based on the family history rather than theory.
• Used for complex multifactorial conditions (compare to Mendelian inheritance which can be determined theoretically).

Question 11

How does the method by which we identify the genetic factors involved in a mendelian condition differ from that of a multifactorial condition?

Answer 11

With a Mendelian condition, you would analyse within a family, whereas for a multifactorial condition, you would analyse within a group of unrelated patients.

Question 12

Define association.

Answer 12

The occurrence of two or more traits in a population that is more frequent than can be readily explained by chance.

Question 13

What is an association study used for?

Answer 13

• To identify genetic factors involved in common conditions.
• To answer the question ‘do people with a condition share a particular DNA pattern?’.
• Compare SNPs between group of patients with the disease and a control group.

Question 14

What is the International Hapmap project?

Answer 14

A project to map human DNA variants for researchers to use in finding genes predisposing to disease.

Question 15

What is a single nucleotide polymorphism (SNP)?

Answer 15

A substitution of a single nucleotide that occurs at a specific position in the genome, where each variation is present to some appreciable degree within a population.

Question 16

Why might it be useful to identify SNPs that are more common in people with a particular genetic disease?

Answer 16

1 - The SNP may be a direct cause of the disease.

2 - The SNP may act as a marker of other genetic factors in that chromosomal region (e.g. controlling elements or protein coding-genes).

Question 17

What is the difference between genomics and genetics?

Answer 17

• Genomics uses many pieces of genetic information to refine treatment.
• Genetics is used where changes to just one pair of genes results in a condition.