Multifactorial Inheritance Flashcards
What is the difference between a multifactorial and polygenic trait?
Multifactorial - includes environmental factors and other triggers, as well as genetic influence
Polygenic - includes only the additive effect of several unspecified genes, no environmental
How are continuous or quantitative traits distributed, and what is considered abnormal?
Measured with a normal curve, abnormal is greater than 2 standard deviations from the mean
What model is used to graph qualitative traits, and what is an example of variable expressivity?
The multifactorial threshold mold, which graphs if traits are present or absent. Variable expressitivity can show the degree of severity a particular trait is, for instance unilateral vs bilateral cleft lip
At what point on the multifactorial threshold model will individuals have a particular trait?
There is a susceptibility based on number of genes which add to cause a particular condition. Once the threshold of liability is passed, individuals will be susceptible to have a trait
How is the multifactorial threshold model changed according to sex (if one has higher incidence than the other) or there is another first degree relative affected with the condition?
Sex: if males have higher incidence than females, their threshold will be lower
If a first degree relative is affected, the threshold will be unchanged but the entire curve will be shifted to the right (higher risk) as compared to normal distribution
What is heritability?
A variable between 0-1 which measures if the variation in a trait within a group of people is due to genetics or the environment. Lower = less heritable
How is heritability calculated for a continuous trait?
H2 = 2(MZ correlation coefficient - DZ correlation coefficient)
If monozygotic twins are more closely correlated than dizygotic twins, the trait is more heritable and this number will be higher. 0.5 is taken as the threshold for when something is considered highly heritable for not
How is heritability calculated for a discontinuous trait?
Concordant vs Discordant. Concordant = the two twins share the trait (have or not). Discordant = one has and one does not.
If Concordance is 100% in MZ and 50% in DZ, highly likely it’s genetic
If there is greater concordance in MZ than DZ in general, there is likely a genetic component.
No difference or low concordance = probably environmental
What is family aggregation?
When there are more cases of a given disorder in close relatives of a person than in control families
What type of study is used to study family aggregation? What can this not rule out?
Case control studies
This cannot rule out environmental factors within the family are a major cause of disease
What is relative risk and how is it calculated?
Relative risk is risk comparing two groups of people, most commonly a given family vs the general population. Commonly calculated in case control studies
Calculation:
Relative risk = (incidence in relatives of a proband)/(incidence in general population)
1 = no difference. Rarely will you have lower than 1
What is the utility of adoption studies?
Can help show the genetic component of some diseases. Compare adopted children from a parent with schizophrenia to adopted children from a parent without schizophrenia, and see if the relative risk is higher.
What is a GWAS? How does this work?
Genome Wide Association Studies. Compare groups of people with a disease to similar groups of people without a disease. See if there is a DNA sequence variation held in common between affected and control groups, and this single nucleotide polymorphism may be inherited with the disorder and correlated with it (not causative)
If an SNP is not causative of the disease condition, what must exist to explain the findings of a GWAS?
Linkage disequilibrium -> the SNP is disproportionately inherited with a mutant allele (not independently assorting)
If the risk of a multifactorial trait in the general population is 1/150, what is the approximate recurrence risk of this trait in a first degree relative of an affected individual? Second degree relative?
Approximately the square root, which is ~1/12
Second degree relatives can be ignored -> approach population risk
What is empiric risk?
Risk derived from familial aggregation studies, not necessarily specific for a particular family
Give two modifiers of recurrence risk?
- It is higher with a greater number of affected relatives
2. The more severely affected the proband, the higher the recurrence risk (higher genetic liability)
If males are more commonly affected than females for a condition, who is it at the greatest recurrence risk? What is an example of this condition?
Sons of affected mothers (they have the highest genetic susceptibility threshold and are yet still affected)
Example: Pyloric stenosis - hypertrophy and hyperplasia of smooth muscle leads to projectile vomiting
What are the two most common neural tube defects?
- Spina bifida - myelomeningocele
- Ancephaly
Failure of neural tube to fuse in the 4th week of embryogenesis
List the genetic etiologies of neural tube defects
- Trisomy 18
- Trisomy 13
- Meckel-Gruber syndrome
Higher prevalence in certain ethnic groups
What is a common teratogenic cause of neural tube defects?
Valproic acid - an anticonvulsant
What is the recurrence risk for NTDs for 1st degree relatives?
3-5%, incidence in general population is 1/1000. If two siblings were affected, it goes up to 10%
What are some environmental factors which can cause NTDs?
Diabetes, obesity, seasonal variation, folic acid deficiency, maternal valproid acid use
What is used to detect NTDs?
- Elevated alpha-fetoprotein in maternal serum
- Amniocentesis, checking acetylcholinesterase levels
- Ultrasound
