Genetics/Biochem Flashcards
Co-dominance + Examples
Both alleles contribute to the phenotype of heterozygote
e.g. Blood groups A, B, AB and alpha 1- antitrypsin deficiency
Variable Expressivity
Phenotype varies among individuals with the same Genotype.
e.g 2 patients with NF-1 (chromosome 17) have varying dz severity
Incomplete penetrance
not all individuals with a mutant genotype show phenotype.
e.g BRCA 1 carriers do not always develop Breast Cancer
Pleiotropy
One gene contributes to multiple phenotypic effects.
e.g untreated PKU, manifests with light skin, musty odor. and intellectual disability.
1 gene = multiple symptoms
Anticipation + name 4 dz that shows and expansion
Increased severity or earlier onset of disease in succeeding generations….
Trinucleotide repeat diseases:
Huntingtons Dz (CAG expansion on chr. 4) Fragile X syndrome (CGG expansion, X-linked) Friedrich Ataxia (GAA expansion on Chr. 9) Myotonic Dystrophy ( Aut. Dom CTG)
Loss of heterozygosity
patient inherits or develops a mutation in a tumor supressor gene the complementary allele must be deleted/mutated for cancer to develop. (2 hit hypothesis of TSG)
Retinoblastoma, HNPCC, Li-fraumeni
Dominant Negative Mutation
Dominant effect - heterozygote produces a nonfunctional altered protein that also prevents the normal gene from functioning.
e.g mutant transcription factor can still bind DNA preventing wild type from binding.
Linkage Disequilibrium
Tendency for certain alleles at 2 linked loci to occur together. more or less often than expected by chance.
measured in a population no family.
Mosaicism
Associated Dz and symptoms
Presence of genetically distinct cell lines in the same individual.
Somatic mosaicism- Mutation arises from mitotic errors after fertilization and propagates through multiple organs/tissues.
Gonadal Mosaicism - mutation in only egg or sperm cells.
McCune-Albright Syndrome- due to mutation affecting G-protein signaling
- unilateral cafe au-lait
- polyostotic fibrous dyslasia,
- precocious puberty
- endocrine abnormalities
Locus Heterogeneity
Example of Associated Dz
Mutations at different loci can produce similar phenotype.
Different loci = similar phenotype
Albinism
Allelic Heterogeneity
Example of Associated Dz
different mutations in the same locus produce same phenotype.
Different mutation + same loci = same disease
B- Thalassemia
Heteroplasmy
Presence of both normal and mutated mtDNA resulting in variable expression in mitochondrially inherited dz.
(mosaicism of mtDNA)
Uniparental Disomy and associated disorder.
- offspring receives 2 copies from 1 parent and none from the other.
- Heterodisomy (heterozygous) = meiosis 1 error
- Isodisomy (homozygous) = meiosis 2 error or
postzygotic duplication of 1 and loss of the other.
Consider UPD in a patient manifesting a recessive disorder when only 1 parent is heterozygote
(other is Homo dom)
25% of prader willi is UPD
Imprinting
at some loci - only 1 allele is active and other is inactive (imprinted via methylation)
Prader willi and Angelman syndrome are due to mutation or deletion of Chr. 15
Southern Blot
DNA technique.
1. DNA sample is enzymatically cleaved into pieces then separated by gel electrophoresis,
then transferred to a filter.
- Filter is exposed to radio-labeled DNA probe that recognizes and anneals to its complementary strand
- Double stranded, labeled piece of DNA is visualized when filter is exposed to film.
Northern Blot
RNA technique
- Similar to Southern blot, but RNA is electrophoresed.
Useful for studying mRNA levels which is reflective of Gene expression.
Western blot
Sample protein is separated via Gel electrophoresis then transferred to a membrane.
Labeled antibody is used to bind to relevant protein.
Confirmatory test for HIV after +ELISA
Southwestern Blot
Identifies DNA binding proteins. Like transcription factors. using labeled oligonucleotide probes
PCR
procedure used to amplify a desired fragment of DNA.
Diagnostic tool.
- dsDNA + DNA primer + nucleotides mixed
- DNA is denatured
- Heating to 95 deg. C- this separates the strands - Annealing
- During cooling to 55 deg. C excess DNA primers anneal to a specific sequence on each strand to be amplified. - Elongation
- Heat Stable DNA polymerase at 72 deg. C replicates the DNA sequences following each primer.
Flow Cytometry
Technique to assess size granularity and protein expansion. Immunophenotype of individual cells.
Used in hematologic abnormalities.
Cells are tagged with antibodies specific to surface or IC proteins. Analyzed 1 cell at a time by focusing laser and measuring light scatter.
Microarrays
Thousands of Nucleic acid sequences are arranged on grids.
DNA or RNA probes are hybridized to the chip and scanner measures complimentary binding.
Able to detect Single nucleotide polymorphisms (SNPs), Copy number variations (CNV)
- genetic testing, forensics, cancer mutations.
Cre-lox system
inducibly manipulate genes at specific developmental points - to study gene that causes embryonic death
RNA interference
dsRNA is synthesized that is complementary to mRNA sequence of interest, dsRNA insertion and separates which promotes degradation of target mRNA.
Autosomal Dominant Diseases
Marfans Spherocytosis
Osteogeneisis imperfecta Tuberous sclerosis
Cholesterolemia (type II) Adenosis Polyposis
Huntingtons/VHL NF1/NF2
ADPKD/achondroplasia(Chr.4) Dystonia Myotonic
