Exam #5: Review Flashcards
Allele Heterogeneity
- Different mutations in the same gene cause different phenotypes
- Beta-Thalassemia
Locus Heterogeneity
- Mutations in different genes cause the same phenotype
- Albinism
Modifier Genes
The individual genetic background modifies the phenotype
Proband
The particular person being reported on
Polymerase Chain Reaction
Molecular biology lab technique used to amplify DNA
1) Denaturation= DNA is denatured by heating to make two separate strands
2) Annealing= premade primers/ oligonucleotides anneal to a specific sequence on each strand to be amplified
3) Elongation= heat stable DNA polymerase replicates the DNA between the primers
Mnemonic for Bolts
SNoW DRoP
Southern= DNA Northern= RNA Western= Protein
Southwestern Blot
Identifies DNA-binding proteins
Microarrays
- Thousands of nucleic acid sequences are arranged in grids on glass or silicon i.e. “chip”
- DNA or RNA probes are hybridized to the chip
- Scanner detects complimentary binding
- Used to detect SNPs or CNV
ELISA
Used to detect the presence of either a specific antigen (direct/ sandwich) or antibody (indirect) in a patient’s blood
Direct/ Sandwich ELISA
- Uses a test antibody to see if a specific antigen is present in the patient’s blood
- A second antibody is coupled to a color-generating enzyme to detect the antigen/primary antibody
Indirect ELISA
- Uses a test antigen so see if a specific antibody is present in the patient’s blood
- A secondary antibody coupled to a color-generating enzyme is added to detect the first antibody
FISH
- Fluorescent DNA or RNA probe binds to a specific gene site of interest on a chromosome
- Used for localization of genes & direct visualization of anomalies (micodeletions)
- Fluoresce= gene present, No Fluoresce= NOT present
Karyotyping
- Process in which metaphase chromosomes are stained, ordered, & numbered according to morphology, size, arm-length, and banding pattern.
- Can be performed on blood, bone marrow, amniotic fluid, or placental tissue.
- Used to diagnose chromosome imbalances
Codominance
- Both alleles contribute to the phenotype of the heterozygote
- E.g. Blood groups
Variable Expressivity
- Phenotype varies among individuals with the same genotype
- E.g. NF-1
Incomplete penetrance
- Not all individuals with mutant genotype show the mutant phenotype
- E.g. BRCA1 gene mutations do not always result in breast or ovarian cancer
Pleiotropy
- One gene contributes to multiple phenotypic effects
Anticipation
- Increased severity or earlier onset of disease in succeeding generations
- Trinucleotide repeat disorders (Huntington’s Disease)
Loss of Heterozygosity
- Patient inherits or develops a mutation in a tumor suppressor gene; the complementary allele must be deleted/mutated before cancer develops
- NOT true of oncogenes
- E.g. Retinoblastoma (Two-Hit Model)
Dominant Negative Mutation
- Exerts a dominant effect. A heterozygote produces a nonfunctional altered protein that also prevents the normal gene product from functioning.
- Collagen proteins
Linkage Disequilibrium
- Tendency for certain alleles at 2 linked loci to occur together more often than expected by chance in a population
Mosaicism
- Presence of genetically distinct cell lines in the same individual. Arises from mitotic errors after fertilization.
- Somatic mosaicism= mutation propagates through multiple tissues or organs
- Gonadal= mutation only in egg or sperm cells
Uniparental Disomy
- Offspring receives 2 copies of a chromosome from 1 parent & no copies from the other
- Uniparental is eUploid (normal #, not aneuploid)
- Consider in an individual manifesting a recessive disorder when only one parent is a carrier
Hardy-Weinberg Equation
p^2 + 2pq + q^2= 1
Hardy-Weinberg Assumptions
- No mutation occurring at the locus
- Natural selection not occurring
- Completely random mating
- No net migration
Imprinting
- At some loci, only one allele is active
- The alternate allele is inactivated by methylation, or “imprinted”
- Disease results when there is a mutation or deletion of the active gene
Prader-Willi Syndrome
- Paternal gene is deleted/ mutated (chromosome 15)
- Results in hyperphagia, obesity, intellectual disability, hypogonadism, & hypotonia
AngelMan Syndrome
- Maternal gene is deleted/mutation (chromosome 15)
- Results in inappropriate laughter, seizures, ataxia, & severe intellectual disability
Autosomal Dominant Inheritance
- Often due to defects in structural genes (but also signaling, growth differentiation, & development)
- Many generations affected
- Both males & females affected
Autosomal Recessive Inheritance
- 25% of offspring from 2 carrier parents are affected
- Often enzyme deficiencies
- Usually seen in only one generation
- Increased risk with consanguineous families
X-Linked Dominant Inheritance
- Transmitted through both parents
- Mothers transmit to 50% of daughters
- Fathers transmit to all daughters but NO sons
X-Linked Recessive Inheritance
- No male-to-male transmission
- Sons of heterozygous mothers have a 50% chance of being affected
- Commonly more severe in males
Mitochondrial Inheritance
- Transmitted only through the mother
- All offspring of affected females may show signs of disease
