ALA Pedegrees And Genetics Flashcards
Two methods for prenatal diagnosis
1) chorionic villus sampling (CVS)
- take a piece of the villa us chorion to use for genetic testing
2) Amniocentesis
- take the amnotic fluid to use for genetic testing
Preimplantation genetic diagnosis (PGD)
Is used by taking 1 blastomere or 5 trophoectoderm cells from a blastocyst to test for genetic anomalies
- ones that do have the genetic abnormality = throw away
- ones that dont have it = good to use
this is done in mothers that known they have predisposition to genetic diseases who want to get tested to make sure the fetus wont have it
What are noninvasive testing for Down syndrome?
HCG = elevated
Cell free DNA shows excess DNA in chromsome 21 sample
AFP = decreased
Inhibit A levels = increased
Unconjugated estriol levels = decreased
What AFP marker level signals spina bifida
Greater than 4
NIPS/fetal cell free DNA
Uses maternal serum to map chromosome of origin and can detect numerous aneuploidies
Use fraction of molecules in each chromsome map and measure the total amount of DNA in patient sample to known normal amounts of chromsome to detect excess/loss of chromosomes
- 13/18/21 and X are used most
Ultrasonography in prenatal screening
Is used often to look for anatomical abnormalities in fetus
Who should be offered genetic counseling
Family history of genetic disorder
Pregnancy over 35
Repeated miscarriages/previous child with genetic disorder
Abnormal US or pregnancy screening
Population vs communities
Population = number of individuals of a species in a given area
- distribution within that area
Community = all members of all species in a area
- population size and distribution and behavior with interactions are key factors (increases transmission
Founder effect and genetic drift and mutation definitions
Mutation = de novo mutation rates consistant amoung populations
- intrinsic error rate in DNA polymerase = 1x10^6
Founder effect = one member of a small community carries a trait, its frequency expands in the next community generation
- usually occurs after a a genetic drift
Genetic drift = dramatic change in allele frequency based on chance
- there is a tendency to knock out lower fitness alleles**
- small populations are more vulnerable
Natural selection, bottle neck and gene flow definitions
Natural selection = increase in allergic frequency that creases a given species fitness level.
- a decrease in frequency decreases the species fitness level
Bottleneck = disrupted allelic frequencies or loss of a geneotype altogether by chance even if the alleles offer equal fitness**
Gene flow = transfer of alleles from one population to another
- is linked to migration
Single gene defect examples
All can be autosomal dominant, autosomal recessive or X-linked inheritance patterns
- all follow Mendelian inheritance patterns
Cystic fibrosis
Hemochromatosis
Tay-sachs
Congenital deafness
Sickle cell anemia
Familial Hypercholesterolemia
Duchenne muscular dystrophy
Hunting ton disease
Marfan syndrome
Fragile X syndrome
A/b thalassemias
Types of non-Mendelian inheritance
Incomplete dominance: the carrier has its own phenotype
- sickle cell and beta thalassemia
Codominance: both alleles contribute to the phenotype of a heterozygote
- blood groups, HLA’s, a1-antitrypsin deficency
Imprinting/uniparental disomy: one gene copy is silenced by methylation and the other is expressed double
- prader-willi and angelman syndrome
Environmental effects: environmental roles palsy an effect on allele
- weight/obesity
Lethal alleles = homozygous dies
- dominant = Huntington’s, recessive = CF
Continuous variation/ expressivity= same genotype can have multiple phenotypes
- NF1, Marfan syndrome
Pleiotrophy = one gene contributes to multiple phenotypic effects
- untreated PKU, collagen disorders
Penetrance = the degree in which a mutant geneotype shows a mutant phenotype
- complete = NF1 and achondroplasia FGFR3 gene mutations
- incomplete = BRCA1/2 genes
Linkage disequilibrium = tendency for certain alleles at two linked loci are expressed more or less often but chance. Is measured by populations not families
Multifactorial inheritance disorders
A combination of environmental factors and mutations in multiple alleles contribute to a disease state
What should be induced in the calculation of genetic risk in an individual?
Results of genetic testing
Any indecent risk factors from genetic test results
Genetic test results on either or both parents, siblings or close relatives
Parents ethnic backgrounds
An overall mutation rate for each ethnicity
Frequency of mutation in the local population
Bayes theorem
The probability of a disease or condition after having performed a test depends on the following
1) the specifics and sensitivity of the test used
2) prior probability of the disease or condition being present BEFORE conducting the test
Realistic perception of risk can greatly impact patient outcomes
