multifactorial inheritance Flashcards
1
Q
multifactorial conditions
A
- Diseases that are due to a combination of genetic and environmental factors
- Most common diseases are multifactorial
2
Q
how do you identify that a condition has a genetic component?
A
family studies, twin studies, adoption studies
3
Q
family studies
A
- Compare the incidence of a disease amongst the relatives of an affected individual with the general population
- The risk of the condition in relatives of an affected individual is dramatically higher than in the general population
- The risk varies with the severity of the proband’s illness
- The risk varies with the number of relatives affected
4
Q
Twin studies
A
- Compare genetically identical (MZ) with genetically non-identical (DZ) twins
- The concordance rate is the % of twin pairs studied that both have the condition. If a condition has a genetic component you would expect the concordance rate to be higher in monozygotic twins than in dizygotic twins. The concordance rates give a rough figure for the hereditability of a multifactorial disorder
- The high risk for MZ twins is found even when they are reared apart
5
Q
adoption studies
A
- Adopted children of a parent with a multifactorial condition have a high risk of developing the disease
- Compare above with a group of adoptees with normal biological parents and an adoptive parent with the condition-they have a low risk
- Can look at adopted individuals with a condition and look at the rates of that condition in the biological and adoptive families – high in the biological families only
6
Q
hereditability
A
- The proportion of the aetiology that can be ascribed to genetic factors as opposed to environmental factors
- Expressed as a proportion of 1 or as a percentage e.g. in schizophrenia hereditability is about 0.85 or 85%
- One way to calculate the hereditability Is from the concordance rate in monozygotic twins
7
Q
characteristics of multifactorial inheritance
A
- The incidence of the condition Is greatest amongst relatives of the most severely affected patients
- The risk is greatest for the first degree relatives and decreases rapidly in more distant relatives
- If there is more than one affected close relative then the risk for other relatives are increased
- If the condition is more common in one particular sex, then relatives of an affected individual of the less frequently affected sex will be at higher risk than relatives of an affected individual of the more frequently affected sex
8
Q
liability/threshold model
A
- Factors that influence the development of multifactorial disorder, genetic and environmental can be considered as a single entity known as liability
- The liabilities of all individuals form a continuous variable which has a normal distribution
- The curve for relatives is shifted to the right compared to the general population
- The closer the relationship the greater the shift to the right
- A threshold exists above which the abnormal phenotype is expressed
- In the general population the proportion beyond the threshold is the population incidence and among relatives is the familial incidence
9
Q
GWAS - genome wide association studies
A
- Utilises the fact that a gene can have several variants – alleles
- Some variations in a gene cause that gene to be inactivated or behave abnormally- pathogenic
- Most genetic variation still results in a functioning gene- polymorphisms
- Different types of polymorphisms – e.g. SNPs (single nucleotide polymorphisms), differing lengths of a CA repeat
- Not all normal alleles of a gene are equal
- Compare the frequency of markers in a sample of patients and a sample of healthy controls. Can use candidate genes or nowadays try to aim for complete coverage of the genome
- Look for markers e.g. a SNP that is seen more frequently In the disease population
- Sequence that area to try to identify the gene and the particular allele that is associated with the increased likelihood of developing the condition
10
Q
neural tube defects
A
- Defective closure of the developing neural tube during the first month of embryonic life
- Recurrence risks are about 4-5% without treatment, highest in people of Celtic origin
- In Ireland about 10% of cases can be attributed to mutations in the methylenetetrahydrofolate (MTHFR) gene which leads to decreased plasma folate levels
- Environmental factors include poor socioeconomic status, multiparity and valproate
- Periconceptual folate supplementation reduces recurrence risk about 1%
11
Q
environmental agents acting on embryogenesis
A
- Drugs and chemicals e.g. thalidomide, anticonvulsants, alcohol
- Maternal infections e.g. rubella, CMV
- Physical agents e.g. radiation
- Maternal illness e.g. diabetes, phenylketonuria
12
Q
post-natal environmental factors
A
- Type 2 diabetes – obesity
- Breast cancer – hormonal factors e.g. the pill, HRT, breast feeding, obesity
- Lung cancer – smoking
- Schizophrenia – recreational drugs
