Risk Assessment Flashcards
How do you calculate frequency of an allele?
Count. 2x homozygous and 1x heterozygous. Add up and divide by total number of alleles in population
What must be known to use counting methods?
Phenotypes need to be identifiable
Frequently, the possible genotypes are NOT all
phenotypically distinguishable without specialized testing
Hardy-Weinberg principle is?
A mathematical statement of the
relationship between genotype frequencies
and allele frequencies at a Mendelian locus.
Frequency of A? Frequency of a?
A=p (dominant)
a=q (recessive)
What is true about p and q?
p+q=1
Frequency of the alleles
Freq of AA? Freq of Aa? Freq of aa?
AA = p^2 Aa = 2pq aa = q^2
For autosomal genes what can be said about sum of frequencies?
(p+q)^2=1=p^2+2pq+q^2
This can be expanded for any number of alleles e.g. (p+q+r)^2=p^2+q^2+r^2+2pq+2pr+2qr
CF is inherited as?
Autosomal recessive
Disease prevalence of CF in northern european white? Carrier prevalence?
1/2500 (i.e. q^2=1/2500)
Carrier is thus 2pq=1/25
Why calculate carrier risk if carrier testing is available?
An accurate understanding of the carrier risk is
important for genetic counseling prior to carrier
testing:
- Understanding of the inheritance pattern
- Perception of risk
- Decision-making about carrier testing
- Waiting period for results of carrier testing
- Carrier testing may not be 100% sensitive
For autosomal recessive disease, if you know parent/patient is not affected, what is risk of carrier or absent (if known that the parents are obligate carriers)
2/3 carrier
1/3 none
Remove the option of being affected in probability
Assumptions of Hardy-Weinberg
•No mutation at the locus.
•No selection for any of the genotypes at the locus
•No migration into the population.
•Mating is completely random with respect to
genotype
What is heterozygote advantage?
Certain mutant alleles may be deleterious in homozygotes but confer increased fitness in heterozygotes.
Sickle cell disease
What is founder effect?
A high frequency of a mutant gene in a population
founded by a small ancestral group
Hardy Weinberg and Consanguinity?
DO NOT USE HARDY WEINBERG
Use mendelian counting instead
What is genetic testing?
The use of specific genetic tests or
assays to determine the genetic status of an
individual already suspected to be at high risk for
developing (or transmitting) a particular inherited
condition because of family history or clinical
symptoms.
What is genetic screening?
The use of specific genetic tests
or assays on a population basis, to identify individuals at risk of developing or transmitting a specific disorder, independent of clinical symptoms or a family history of the disorder.
Settings for genetic screening?
- Newborn
- Prenatal
- Carrier (heterozygote)
- Gamete donors
- Epidemiological
- Occupational
Major principles of screening?
Absence of compulsion
-testing must be voluntary
- program must not stigmatize or impose constraints on
childbearing or mate selection
Protection of participants
- informed consent essential
Privacy and access to information about results
- results available only to screenee
Community involvement in :
- planning
- education about program and impact of results
Equal access
to information about screening, testing, and test facilities
General criteria for genetic screening?
-Severe, relatively common, well-understood disease
-Identifiable high-risk population
-An acceptable screening test
-Easy to perform
-Inexpensive
-Good validity and reliability
-More specific additional tests are available to confirm
or rule out the diagnosis.
- Useful and realistic interventions are available
-Effective therapy
-Reproductive options
-Risk reducting strategies
What is clinical validity?
The extent to which a test result is predictive
for disease
What is clinical utility?
The degree to which test results will change
what medical care an individual receives, and
improves the outcome of care.
What does clinical validity depend on?
- Sensitivity
- Specificity
- Positive predictive value
