Multifactorial and Common Complex Conditions NOT FINISHED

Question 1

What is the difference between mendelian and non-mendelian inheritance?
Give examples of conditions that fit under these headings

Answer 1

Mendelian - caused by mutation in one copy or both copies of a single nuclear gene. classical inheritance patterns, dominant/recessive/x-linked/autosomal
Generic componet highlighted by pedigree pattern and recurrence risk
e.g. hypercholesterolaemia, marfan syndrome, cystic fibrsos, sickle cell, duchenne, some diabetes

Non-mendelian - multifactorial inheritance and maternal inheritence, polygenic
Genetic components suggested by clustering of cases in some families but no obvious inheritence pattern.
e.g. CAD, diabetes mellitus, hypertension, cerebrovascular disease, schizophrenia, breast/bowel cancer, some congenital anomalies

Question 2

How are genetic and environemental influences identified?

How is evidence gathered for genetic factors in complex diseases?

Answer 2

observational studies of the indcidence of diseases in different groups of people

familial clustering
twin studies
adoption studies
population and migration studies

Question 3

The following conditions all show …….. distribution in the general population:

• blood pressure
• dermatoglyphics
• head circumference
• height
• intelligence
• skin colour

Answer 3

normal

Question 4

What is the basis of multifactorial inheritance?

What is a clinical clue?

Answer 4

inheritence controlled by many genetic factors with small additive effects (polygenic)
plus the effects of the environment
Clinical clue: one organ system affected

Question 5

What are the genetic and environmental factors that can contribute to neural tube defects?

Answer 5

Genetic
- celtic origin
- specific variant in folate receptor
Environmental
- poor socioeconmomic status
- multiparity (pregnancies)
- valproic/folic acid periconceptually

Question 6

What is recurrence risk?

Answer 6

The probabilty of having another child with the same condition

Question 7

What factors would increase probability of recurrence in a particular family?

Answer 7

close relationship to person with condition
high heritability of condition
person with condition of more rarely affected sex
severe or early onset disease
multiple family members affected