Sollars - Combined Flashcards
What can be said on the distribution of mitochondrial genomes?
2 - 10 copiesCytoplasmic segregationHeteroplasmy (uneven distribution)
What pathology is common in mitochondrial DNA disease?
Liver pathology
For MtDNA disease, what is the effect of Heteroplasmic vs Homoplasmic?
Heteroplasmic is rare, and strong (multisystem, death)Homoplasmic is more common, and weaker (associated w/disease)
Why would someone being treated for HIV-1 or Hepatitis B be affected by Mitochondrial DNA Depletion?
gamma-Pol resembles HIV polymerase (which we attack)
What do MtDNA diseases in the exonuclease domain deal with?
Proofreading—fidelity
What do MtDNA diseases in the polymerase domain deal with?
Efficiency
What is the role of y-Pol (gamma)?
Replicates MtDNA
What can occur when checks in the cell cycle to not properly occur to ensure fidelity of genome?
Cancer
What is faster, prokaryotic or eukaryotic DNA replication?
Prokaryotic (50 bp/s vs 1000 bp/s)
If you see a DNA Pol + Greek symbol, what are you dealing with?What about a Roman numeral?
Eukaryote = GreekProkaryote = Roman
What enzyme acts on the unrprotected end of linear chromosomes? What other problems can occur
ExonucleaseChromosomal fusion events
Cellular Senescence
Phenomenon which normal cells cease to divide, possibly triggered by gradual loss of telomere
Cellular Crisis
When Cellular Senescence does not occur, and cells continue to divide–can lead to mutation events and cancer
Telomerase
Enzyme to replicate end of chromosomes
When will a cell enter Senescence?
When it reaches Telomere Associated Repeats (TAR)
What is the mechanism for Telomere building?
After removal of original RNA primer, will have stretch of ssDNA1. Telomerase contains RNA template matching telomeric repeat element2. ssDNA above is extended farther3. Primase synthesized RNA primer4. 3’ ends of primer accepts DNA polymerase5. RNA primer removed from 5’ end
Fragile Sites
Non-staining gaps, observed in characteristic sites on several chromosomes.
How are fragile sites inherited?
Mendelian codominant fashion
When would chromosomes be visible in the classic fashion?
After S-Phase
What is the purpose of the centromere?
Attachment of chromosomes to cytoskeleton
What 3 things do you need for chromosomes?
CentromereTelomereOrigin of Replication
What are three morphological classifictions of chromosomes?
MetacentricSubmetacentricAcrocentric
Satellite DNA
Any fraction of the DNA that differs sufficiently in its base composition from that of the majority of the DNA fragments to separate as one or more bands distinct from the bands containing the majority of the DNA during centrifugation
When does each chromosome have an identical nucleoprotein copy joined by a centromere (sister)?
After S-phase and DNA replication
Replication of Origin
Nucleotide sequence at which DNA synthesis begins
Type of Chromosome w/a centrally placed centromere =Type of Chromosome that appears J-shaped at anaphase because the centromere is nearer one end than the other =Type of Chromosome with a nearly terminal centromere =
MetacentricSubmetacentricAcrocentric
Complex of nucelic acids (DNA/RNA) and proteins (histones/nonhistones) comprising eukaryotic chromosomes
Chromatin
What type of chromatin is highly condensed and shows no evidence of active gene expression?What type contains transcriptionally active DNA and is extended?
HeterochromatinEuchromatin
How many chromosomes does a haploid cell contain?
23
What is the structure of mitochondrial chromosomes?
Circular
What is the difference between Unique Sequence DNA and Repetitive DNA?
Unique = single copy per haploid genome, low conservation, protein coding, intronic, intergenicRepetitive DNA = Repeated sequences, >50% of genome
Satellite DNA
Any fraction of the DNA that differs substantially in base comp (either A+T rich, or G+C rich); formsbands
Short Interspersed Nucleotime Elements (SINES)andLong Interspersed Nucleotide Elements (LINES)
SINES:AlurepeatsLINES: L1 (Line-1)Both are Dispersed Repetitive DNA
What are major differences between mitochondrial DNA and Nuclear Genome?
Mitochondrial genome is 10,000x smaller; each cell contains thousands of copies; is highly conserved for coding; and displays maternal inheritanceNuclear genome is much larger but only contains two copies and displays traditional maternal/paternal inheritance
What is the most common cell used for chromosome preparation?
Circulating Lymphocytes
What cell cycle would you stop the cell at in order to best study the chromosomes?
Metaphase
Define each number for the following gene:10p23
10(chromosome) p(arm) 2(region) 3(band)Hint: Remeber C.A.R.B
What type of study is treatment with trypsin following by staining with Wright’s (Giemsa)?What is characteristic of this study?
G-bandingCharacteristic, and reproducible patterns of light and dark bands
What type of study features fluorescent dye binding to A-T rich regions preferentially?
Q-banding
What technique freezes cells earlier in their cycle, and is useful in detecting subtl structural abnormalities?
High-resolution banding (prophase or metaphase banding)
What is the difference between R and G bands?
R = early replication, light bands, genes are mostly concentrated hereG = A-T rich dark bands, few expressed genes, rich in L1 sequences
What type of band is light, G-C rich, contains expressed genes, and is rich in Alu?
R-band
What type of band is A-T rich, has few expressed genes, and is rich in L1 repeated sequences?
G-bands
Fluorescentin situHybridization (FISH)Commonly used for what?
Analysis method to us a labeled,chromosome specificDNA segment to hybridized with metaphase, prophase, or interphase chromosomes and visualize under a fluorescent microscopeConformation of Down’s syndrome
Spectral Karyotyping (SKY)
Using multiple fluorescent probes specific for each chromosome to generate specific colors along most of its length.Greatly incrased accuracy and efficiency of detecting abnormalities.
Comparative Genomic Hybridization (CGH)
DNA from test source is labeled with a green gluoropore and control normal DNA is labeled with red fluorophores. Two mixed, hybridized to normal chromosomes. Deletions or additions will alter the green:red ratio.Widely used in cancer genetics.
Individualized Medicine
Treating patient based upon biochemistry and genetic factors. “Tailored” medicine
Pharmacogenomics
Study of the role of inherited and acquired genetic variation in drug response
Cytogenetics
Study of chromosome structure and identification of microscopically visible abnormalities. Examination of the ordered array of chromosome or karyotype
Molecular Genetics
Study of structure and function of genes, includes gene mapping and recombinant DNA based tech
Biochemical Genetics
How genetic defects disrupt normal metabolism/cell control–need this to design treatment
Population Genetics
Study of how allele frequencies present in a population.
Clinical Genetics
Diagnosis/detection of inherited disorders; treatment/management; risk assessment; genetic counseling; and pharmacogenomics
Pharmacogenomics
Study of the role of inherited ad acquired genetics variation in drug response
Law of Segregation (1st Law)
Each individual possesses two genes for a particular characteristic. Only one of these genes is transmitted to the offspring
Which law deals with unaffected carriers of disease?
Law of Segregation
Monohybrid cross
Mating cross designed to produce an individual that has parent contributions that are different for one trait
What is the ratio of progreny in the F2 generation?
3:1
What are characteristics that appear in the F2 generation?
Recessive
Dominant
Forms of gene that fully manifest their effects on a trait when present in the heterozygous state
Recessive
Forms of a gene whose effects on a trait are masked by dominant allelles
Codominance
Alleles are codominant if each is expressing independently of the presence of the otherEx: A/B alleles in blood typing
Genotype vs Phenotype
Genotype: Genetic (allelic) composition of individual (Xx, etc)Phenotype: Observable physical, biochemical, etc feature (color, height, etc)
Law of Independent Assortment (2nd Law)
Members of different pairs of factors assort independently.or..Members of different pairs of alleles are assorted independently into gametes during gametogenesis, and that subsequent pairing of male and femail gametes is random.
What is the molecular basis for the law of Independent Assortment?
Genes are present on independent chromosomes, and chromosomes undergo recombination along their length fairly frequently
Epistasis
when one gene masks the expression of anotherEx. Blue eyes
Linkage
greater association in inheritance of two or more nonallelic genes than is to be expected from independent assortment
Genomic Imprinting
– degree of which a gene expresses itself depends upon parent transmitting
Mitochondrial Inheritance
inheritance of a trait encoded in the mitochondrial genome
Germline Mosaicism
when an individual is composed of two or more cell lines in their germ cell population, where these cell lines are of different genetic or chromosomal constitutionex. Seen in schizophrenia
Single Gene Defect
Stem frompolymorphism or mutationsin one gene; easy to recognize modes of inheritanceExamples: Cystic fibrosis, sickle cell, Marfan
Chromosome Disorder
Defect is due not to a single mistake in genetic blueprint, but to an excess or deficiency of genes contained in whole chromosome or chromosome segmentsEx: Down’s, Patau
Multifactorial Inheritance
Most common defect, can include environmental and genetic factors.These can recur in families, but do not show any particular pedigree pattern
What can be useful in determining if disorder is inherited?
Comprehensive family historyMedical literatureTwin studies/segregation analysis