Multifactorial Inheritance Flashcards
What are the classic single gene disorders?
Sickle cell
cystic Fibrosis
duchenne dystrophy
what is a characteristic of Multifactorial traits?
- Trait does not demonstrate a simple mendelian pattern
- Familial aggregation
- More common among the close relatives of the proband and less common in relatives who are less closely related
- Environment also interacts with genotype to produce the final phenotype
What is the model that tries to explain multifactorial traits?
Liability/threshold
attempts to describe a populations genetic and environmental susceptibility.
What is liability?
all factors that contribute to the disease
What is threshold?
The limit to which normal is defined.
Passing threshold will make them affected
Liability in multifactorial diseases
Disease state is determined by both genes and environment
What is this image of?
Liability model and familial aggregation
What happens when there are bad genes in the liability and threshold model?
The curve is moved to the right- more of the population is above the threshold point
The threshold line moves to the left-in essence the same thing as more of the population is under the affected portion of the curve
Relative Risk ratio
Prevalence of disease in relatives of affected person / prevelance of disease in general population
What does the liability threshold model explain?
Explains the pattern of recurrence risk in families
What is Pyloric stenosis? What does it mean is a female has it in regards to recurrence risk?
Hypertrophy of the muscle between the stomach and intenstines,causing it to narrow(stenosis) impeding gastric emptying.
More common in male babies
If a female child gets it, that means there is a higher reccurence risk f because the parents have more of the bad gene
Symptoms of pyloric stenosis
Severe vomiting
palpation of the abdomen may reveal a mass in the epigastrium
may cause other problems such as dehydration and salt fluid imbalances
What are tools for determing the effects of genetic versus environment?
- Population/migration studies
- Family studies
- twin studies
- adoption studies
- Association studies
Population/Migration studies
Indicative of environmental factors.
Disease incidences differences between populations suggest a genetic basis for that disease.
Could be due to cultural/lifestyle differences.
It is known that Asian women have a lower incidence of breast cancer than American women. The Asian women move to America and within two generations, their incidence increased to near american levels. What experiment/study is this an example of?
Population/Migration study.
What is concordance?
Both twins have the same disease
What is Discordance?
One twin has the disease, the other twin does not.
Monozygotic Twin (M.Z)
Derived from a single ovum
Genetically identical
Dizygotic Twins (D.Z)
Derived from two seperate ova but share intrauterine environment.
Have genome similar to being regular siblings.
What is the relationship of concordance between M.Z and D.Z?
The greater the difference in concordance rate between M.Z and D.Z twins= greater genetic input.
What are limitations to twin studies?
- May underestimate heritability
- M.Z do have SOME different genes(like mitochondrial genes) and epigenetic differences
- also different accumulation of somatic mutations due to errors in mitosis
- Different environmental exposures
- Different genes in different twin pairs
- Studies between different sets of twins may point to different contributors for same phenotype
- Ascertainment pairs
- Most studies do NOT specify the loci and alleles but how genotype and environment interact
What is the purpose of Association Analysis?
To test the co-occurence of a specific allele at a marker locus and a trait in a population by comparing the frequency of an allele in patients and controls
What is Genome Wide Association studies?
Compares the genome of people with an illness to unaffected people to identify associations between SNPs and phenotype.
What are two types of neural tube defects?
Anencephaly and Spina Bifida
Anencephaly
Under developed brain and incomplete skull
May have brain stem function
most do not survive more than a few hours after a birth
Spina bifida
Incomplete closure of the spine
Repair may be done in utero or postnatally
can be variable in severity
Spina Bifida and incidence rates
Incidence = (1 to 2) / 1000
Spina Bifida: Evidence for genetics
A woman who has had one child with a neural tube defect such as spina bifida has ~3% risk of having another
Mutations in genes coding enzymes for folate metabolism
Spina Bifida
- Supplementation of the mother’s diet with folate can reduce the incidence of neural tube defects by about 70%
- The 3% risk of the woman having another child with a NTD can be reduced to 1% with high doses of folic acid
