O GoConqr está de visual novo! Conte para nós o que você achou.

Registre-se grátis

Flashcards

Cytogenetics, Genetic Counseling, and Risk Assessment

Farrah Inglês 116 flashcards

Cytogenetics, Genetic Counseling, and Risk Assessment

Flashcards do conjunto (116)

  1. 1Multifactorial InheritanceCondition attributed to the additive effects of genetic and environmental factors
  2. 2Hardy-Weinberg EquilibriumThe relative proportions of each genotype remains constant with frequencies of p^2, 2pq, and q^2 for that particular genotype.
  3. 3Assortative MatingNon-random mating
    Tendency to choose partners who share characteristics such as height, intelligence, or racial origin.
  4. 4ConsanguinityNon-random mating.
    Marriage between blood relatives who have at least one common ancestor no more remote than a great-great-grandparent.
  5. 5Coefficient of RelationshipProportion of alleles shared by TWO individuals sharing common ancestry.
    COR = (1/2)^n
    n = # links via common ancester
  6. 6Coefficient of InbreedingProportion of homozygosity across all loci in ONE individual resulting from related ancestors. Equal to 1/2 of coefficient of relationship.
    COI = 1/2 x (1/2)^n
    n = # of links via common ancester
  7. 7Founder EffectRare allele becomes very common if introduced into a small population, either due to chance or proliferative parent.
  8. 8CentromereHold sister chromatids together.
    Site of kinetochore assembly during cell division.
    Several hundred kilo bases of repetitive DNA and proteins.
    171 bp tandemly repeated alpha-satellite DNA clustered at all human centromeres. with sequence divergence allowing chr-specific FISH probe (except 13 and 21, 14 and 22 too similar for unique hybridization)
  9. 9Metacentric ChromosomeCentromere is located centrally
  10. 10Acrocentric ChromosomeThe centromere is terminally located.
    Chr 13, 14, 15, 21, 22.
    Small p arm comprised of large, tandem arrays of rDNA genes (stalks).
    At end of stalks "satellites" with highly repetitive junk DNA.
  11. 11Submetacentric ChromosomeThe centromere is in an intermediate position.
  12. 12KinetochoreSite for attachment of the chromosome to the mitotic spindle.
    Only present during M phase.
  13. 13TelomeresSeal ends of chromosomes to protect from degradation and end-to-end fusions.
    Tandem repeats of TTAGGG sequence.
    Substrate for telomerase, shortens with age. True terminal deletions can generate new telomeres.
    TAR (telomere associated repeats) are 100-300 kb sutelomeric repeats.
  14. 14TelomeraseReplaces the 5' end of the long strand, which would otherwise become progressively shorter.
    Active in germ cells, stem cells, and certain white blood cells.
    Activation implicated in cancer cell immortalization.
  15. 15InterphasePeriod between successive mitosis.
    Starts with G1 phase of cell growth.
    (Some cells arrest here, G0 phase)
    Followed by S phase of DNA synthesis.
    Completed by short G2 phase.
  16. 16G1 Phase (Gap1)Chromosomes become thin and extended.
    Cellular contents (not chromosomes) are duplicated.
    Variable length. In rapidly dividing cells, this lasts 10-12 hours.
  17. 17S phase (synthesis)DNA replication occurs.
    Chromatin of each chromosome is replicated leading to formation of two chromatids.
    6-8 hours
  18. 18Chromatin fibersTertiary coiling of Nucleosomes (DNA and histone proteins).
  19. 19EuchromatinStains lightly (G-negative).
    Genes that are actively expressed.
    GC-rich.
    Rich in SINE and Alu repeats.
    Replicates early S phase.
    Housekeeping genes.
  20. 20HeterochromatinStains darkly (G-positive).
    Made up largely of inactive, unexpressed, repetitive DNA.
    AT-rich.
    L1 (LINE) repeats.
    Replicates mid-late S phase.
    Genes are tissue specific.
  21. 21G2 Phase (Gap2)Chromosomes begin to condense in preparation for next mitotic division.
    Cell double checks the duplicated chromosomes for error making any needed repairs.
    2-4 hours
  22. 22Embryonic Cell CyclesNo cell growth.
    Very quick cell cycles.
    Only S and M phases.
    No Gap phases (no G1 or G2).
  23. 23Mitosis (M phase)Process of somatic cell division.
    Diploid cell yields 2 diploid cells.
    Pair of chromatids separate and disperse into daughter cells.
  24. 24ProphaseChromosomes condense.
    Mitotic spindle and centromeres form.
    Centromeres go to opposite poles of the cell as microtubules radiate from them.
  25. 25PrometaphaseNuclear membrane dissolves.
    Each chromosome becomes attached at its centromere (kinetochore) to a microtubule.
  26. 26MetaphaseChromosomes aligned at equatorial plane.
    Chromosome centriole attached to microtubule.
    Chromosomes maximally condensed resembling letter X in shape.
  27. 27AnaphaseCentromere of each chromosome divide longitudinally.
    Two daughter chromatids separate to opposite poles.
  28. 28TelophaseChromosomes reach poles and begin to decondense.
    Nuclear envelopes begin to reform around chromosomes.
    Cytokinesis resulting in 2 new daughter cells.
  29. 29MeiosisDivision for gametogenesis.
    One round of DNA synthesis followed by two rounds to cell division.
    A diploid cell leads to four haploid gametes.
  30. 30Prophase IExchange of homologous segments between chromatids by crossing over or recombination (telomere>centromere; overall F>M, at telomere M>F)
    5 stage subdivision: Leptotene, Zygotene, Pachytene, Diplotene, Diakinesis
  31. 31LeptoteneChromosomes begin to condense.
    Homologs align.
  32. 32ZygoteneHomologous chromosomes align directly opposite each other (synapsis), held together by filamentous structures (synaptonemal complexes)
  33. 33PachyteneEach pair of homologous chromosomes (bivalent) are coiled.
    CROSSING OVER OCCURS, DNA exchanged between chromatids.
  34. 34DiploteneHomologous recombinant chromosomes separate, but remain attached where crossing over has occurred (chiasmata).
  35. 35DiakinesisSeparation of homologous chromosome pairs.
    Chromosomes maximally condensed.
  36. 36OogenesisMitotic division in fetal development.
    Primary oocyte arrested in Meiosis I (Prophase I, diplotene = dictyotene).
    At ovulation complete Meiosis I to make a single secondary oocyte & polar body. .
    Meiosis II then commences, during which fertilization can occur.
  37. 37SpermatogenesisBegins at puberty.
    Requires 60-65 days.
    Enter Meiosis I to make secondary spermatocytes.
    Meiosis II forms 4 spermatids which develop into mature spermatozoa.
    Continuous though adult life.
  38. 38Pseudoautosomal regionsHomologous segments of X and Y chromosomes.
    Pair during recombination during spermatogenesis with obligatory recombination in PAR1.
  39. 39ColchicinePrevents formation of mitotic spindle.
    Arrests cell division during metaphase.
    Used to prepare cells for karyotype.
  40. 40Giemsa BandingDNA-binding dye.
    Trypsin technique used for staining to denature protein content.
    Provides 400-500 bands per haploid set.
    Each band is 6000-8000 kb.
    Analytical sensitivity at 5 Mb.
  41. 41Non Allelic Homologous Recombination (NAHR)Unequal crossing-over between misaligned homologous chromosomes or sister chromatids.
    Causes recurrent rearrangements.
  42. 42Non homologous end joiningChromosome breakage followed by abnormal reconstitution.
    External: ionizing radiation, chemicals
    Internal: stressors, breakage syndromes
  43. 43—Reciprocal translocation.
    1:500 individuals carries a balanced reciprocal translocation.
    t(11;22)(q23;q11) most common.    Reciprocal translocation. 1:500 individuals carries a balanced reciprocal translocation. t(11;22)(q23;q11) most common.
  44. 44—Alternate Segregation.
    Normal or balanced haploid complement.    Alternate Segregation. Normal or balanced haploid complement.
  45. 45—Adjacent-1 segregation.
    Unbalanced haploid complement.
    Like centromeres segregate apart.    Adjacent-1 segregation. Unbalanced haploid complement. Like centromeres segregate apart.
  46. 46—Adjacent-2 segregation.
    Unbalanced haploid complement.
    Like centromeres segregate together.    Adjacent-2 segregation. Unbalanced haploid complement. Like centromeres segregate together.
  47. 473:1 Segregation3 chromosomes segregate to one gamete with only one chromosome in other gamete.
    More likely if one translocation product is much smaller than the other product.
  48. 48Robertsonian translocationBreakage of 2 afrocentric chromosomes at or close to their centromeres with subsequent fusion of their long arms.
    Most common 13q14q
  49. 49—Pericentric Inversion.
    During Meiosis I, inversion loop can lead to crossover, deleted & duplicated segments.
    Larger the size, smaller imbalance during crossover -> more likely to result in birth of abnormal infant.
    Smaller the size, large imbalance -> more likely to result in miscarriage.    Pericentric Inversion. During Meiosis I, inversion loop can lead to crossover, deleted & duplicated segments. Larger the size, smalle...
  50. 50—Paracentric inversion.
    Meiosis I crossover in the inverted segment, will result in recombinant chromosomes that are eccentric or dicentric.
    No viable offspring.    Paracentric inversion. Meiosis I crossover in the inverted segment, will result in recombinant chromosomes that are eccentric or dicentri...
  51. 51IsochromosomeLoss of one arm with duplication of the other (centromere divided in the wrong direction).
    Most common is X chromosome long arm.
  52. 52Ring ChromosomesBreak on each arm of a chromosome leaving 2 "sticky" ends that reunite as a ring.
    Two distal chromosomal fragments are lost.
    Unstable in mitosis.
  53. 53Parental origin of 47,XXYPaternal 45%
    Maternal 55%
  54. 54Parental origin of 45,XPaternal 80%.
    Maternal 20%.
  55. 55Trisomy 16Most common autosomal aneuploidy in SAB.
    100% cases from error in maternal meiosis I.
  56. 56XIST (X-inactivated specific transcript)Xq13.3
    Expressed only from inactivated X
    Encodes an RNA product that coats the inactive X.
    Multiple genes escape silencing (~15%)
  57. 57SensitivityFraction of those affected that screen positive.
    Fraction of individuals with disease who have the susceptibility genotype.
    TP / [TP + FN]
  58. 58SpecificityFraction of unaffected that screen negative.
    Fraction without disease who do not have the susceptibility genotype.
    TN/[FP+TN]
  59. 59Positive Predictive ValueFraction of affected with positive screens.
    Proportion of individuals with susceptibility genotype who have or will develop a particular disease.
    TP / [TP+FP]
  60. 60False negative rate1 - sensitivity (TP/[TP+FN])
  61. 61False positive rate1 - specificity (TN/[FP+TN])
  62. 62Probability Law of multiplicationApplies to independent events
    Defined by "both", "and", "all", or "none"
    Probabilities are multiplied
  63. 63Probability Law of AdditionApplies to events that are mutually exclusive.
    Defined using "either" and "or"
    Probabilities are added
  64. 64Carrier risk of AR disorder based on frequencyCarrier risk = square root of 4 x frequency of condition
  65. 65Carrier risk for XLR "lethal" conditionMother carrier risk is 2/3
    Maternal grandmother risk is 1/3
  66. 66Bayesian GridHypothesis: Is, Isn't
    Prior Probability: A, C
    Conditional Probability: B, D
    Joint Probability: AxB=E, CxD=F
    Posterior Probability: E/(E+F), F/(E+F)
  67. 67Prior ProbabilityProbability of a hypothesis (i.e. disease) before additional information is available (i.e. test result)
    Basic Mendelian probabilities
  68. 68Conditional ProbabilityIf the particular hypothesis is true, probability of additional information.
    Reduced penetrance, variability.
  69. 69Joint probabilityPrior x conditional probability
    Probability of the particular hypothesis AND additional information
  70. 70Posterior ProbabilityProbability of the particular hypothesis given additional information = Joint probability of the particular hypothesis divided by the sum of all joint probabilities.
    Fraction of total joint probability that is represented by scenario.
  71. 71Law of UniformityWhen two homozygotes with different alleles are crossed, all of the offspring are identical and heterozygous.
  72. 72Law of SegregationEach person possesses 2 genes for a particular characteristic, only one of which can be transmitted at any one time.
    (rare exceptions - chromosome non-disjunction)
  73. 73Law of Independent AssortmentMembers of different gene pairs segregate to offspring independently of one another.
    (not always true, genes close together are 'linked')
  74. 74NucleosomesDNA helix coiling around spherical histone beads
  75. 75Fluorescent in-situ hybridization FISHDNA probe labeled with fluorochrome.
    Hybridizes with patient's sample.
    Region where hybridization has occurred to be visualized using a fluorescence microscope.
  76. 76Barr bodyInactive X chromosome, forms sex chromatin.
    Visualized during interphase in female somatic cells.
    Always late in replicating.
  77. 77HeteromorphismPericentric inversion involving chromosome 9.
    Common structural variant or polymorphism.
    Not thought to be of any functional importance.
  78. 78Large Pericentric InversionThe duplicated and deleted segments will be relatively small so that survival to term and beyond becomes more likely.
    The larger the size the more likely an abnormal infant will be born.
    As opposed to small inversion that would more likely result in pregnancy loss.
  79. 79IsochromosomesLoss of one chromosome arm with duplication of the other.
    Centromere divided transversely rather than longitudinally.
    Most common is two long arms of X chromosome (15% of Turner syndrome)
  80. 80ChimerismPresence of two or more genetically distinct cell lines derived from more than one zygote.
    Dispermic chimeras - double fertilization. Two sperm fertilize two ova and the zygotes fuse to form one embryo.
    Blood chimeras - Exchange of cells via the placenta between non-identical twins in utero.
  81. 81LyonizationX-chromosome inactivation
    Occurs 15 to 16 days gestation.
    Either of the two X chromosomes can be inactivated, the same X chromosome is inactivated in all daughter cells.
    Abnormal X chromosome will be preferentially inactivated (actually, only those with normal X intact survive).
  82. 82Autosomal DominantVertical transmission. Father to son transmission confirms.
    Child has 50% chance of inheriting disorder or trait.
  83. 83PleiotropyA single gene that may give rise to two or more apparently unrelated effects.
    Manifest in different systems of the body in a variety of ways.
  84. 84Variable ExpressivityClinical features of a disorder show striking variation from person to person even in the same family.
  85. 85Reduced Penetrance'skipping a generation'
    Result of modification effects of other genes, integration of the gene with environmental disorders.
    No features despite inheriting gene is non-penetrance.
  86. 86Co-DominanceTwo allelic traits that are both expressed in the heterozygous state.
    Example: blood group AB
  87. 87PseudodominanceA person homozygous for AR disorder has child with carrier of same AR disorder. Children have 1/2 chance of being affected.
  88. 88Locus heterogenityDisorder inherited in the same manner can be due to mutations in more than one gene.
  89. 89GenocopiesDisorders with the same phenotype from different genetic loci
  90. 90PhenocopySame phenotype of disorder from environmental causes
  91. 91Y-linked inheritance Holandric inhirtanceOnly males are affected.
    Hairy ears.
    H-Y histocompatibility antigen.
    Genes involved in spermatogenesis.
  92. 92Digenic InheritanceDisorder is shown to be due to the additive effects of heterozygous mutations at two different gene loci.
    Example in humans: Retinitis PIgmentosa can be caused by double heterozygosity for mutations in two unlinked genes (ROM1 and Peripherin)
  93. 93Triallelic InheritanceExample: Bardet-Biedl Syndrome that has multiple causative genetic loci. One form occurs when an individual is homozygous for mutations at one locus is also heterozygous for mutation at another Bardet-Biedl locus.
  94. 94AnticipationOnset of the disease occurs at an earlier age or with increased severity in the offspring than in the parents.
    Example: Myotonic dystrophy where CTG repeat expands further during maternal meiosis. Huntington disease where CAG repeat expands further during paternal meiosis.
  95. 95Uniparental isodisomyTwo copies of the same homolog from one parent through an error in meiosis II
  96. 96Uniparental heterodisomyTwo different homologs inherited from one parent due to an error in meiosis I
  97. 97Homoplasmymitochondrial DNA from different mitochondria is identical
  98. 98HeteroplasmyIf mutation occurs in mtDNA, there will be two populations of mtDNA. The proportion of mt with mutation in DNA varies between cells and tissues.
  99. 99Estimating carrier frequencyIncidence for AR disorder in HWE is q^2
    Square root = q. p+q=1. 1-q = p
    Carrier frequency = 2pq
    If p is close to one, rough estimate can be square root of disease incidence.
    For XLR disorder, frequency of affected males = q, affected females = q^2, and carrier females = 2pq
  100. 100Estimation of Mutation RatesDirect: counting new cases in defined number of births. 12 kid with AD condition in 100,000 births. 2 have affected parents. 10 de novo. 10 mutations/200,000 genes.
    Mutation rate of 1 per 20,000 gametes.
    Indirect: AD condition with reproductive fitness of zero (f=0), all cases new mutations. Incidence = I, mutation rate m, each child gets two alleles, either can mutate. I = 2m.
    If fitness greater than zero, genes lost through reproductive fitness must be balanced by new mutations. 2m=I(1-f).
    For AR, m=I(1-f).
    For XLR, m=[Incidence in males x (1-f)]/3
  101. 101PolymorphismOccurence in the population of two or more genetically determined forms
    (alleles, sequence variants) in such that the rarest of them could not be maintained by mutation alone.
    By convention, at least two alleles, each with a frequency greater than 1%.
  102. 102Polymorphic Information Content (PIC)Value of particular polymorphic system is assessed by determining PIC. The higher the PIC the more likely the polymorphic marker will be of value in linkage analysis and gene tracking.
  103. 103Odds RatioRadio of the odds of developing the disease in those with a specific marker to the odds of developing the disease without that specific marker.
  104. 104Genome Wide AssociationCompare variants across the entire genome. Hypothesis-free approach to determine which SNPs are involved in disease. P value threshold lower for statistical significance at 5 x 10^-8. Large sample sizes needed to achieve low P value.
  105. 105Positive Predictive ValueProportion of positive tests that are true positives.
    True Positives/(True Positives + False Positives)
  106. 106SensitivityProportion of cases that are detected.
    True Positives/(True Positives + False Negatives)
  107. 107SpecificityExtent to which the tests detects only affected individuals.
    True Negative/(True negative + False Positive)
  108. 108SyntenicGenes that are on the same chromosome
  109. 109Genetic Information Nondiscrimination Act (GINA)2008
    Private employers with 15 or more employees are prohibited from deliberately seeking or using genetic information, including family history, to make an employment decision. Prohibits most group health insurers from denying insurance or adjusting group premiums based on the genetic information of members of the group.
  110. 110Triploidy69,XXY>69,XXX (69,XYY very rare)
    No risk of recurrence
    Sx: >99% lost 1st trimester, 6-10% all SAB, 16-20% all chromosomally abnl SAB, dysplastic calvaria with large posterior fontanelle, 3/4 finger syndactyly, ASD, VSD, hydrocephalus, holoprosencephaly.
    Mat (digyny): small placenta, severe asymmetric IUGR with a large head
    Pat (diandry): hydropic large placenta, well grown to mod symmetric IUGR, nl or microcephalic head; MOST COMMON
    Eval: low maternal serum hCG
  111. 111Timeline of Cytogenetics1923 - Y chr, 48 chr
    1953 - hypotonic chr spread
    1956 - 46 chr
    1959 - Trisomy 21 down syndrome
    1969-1970 - Banding techniques
    1976-1980 - fragile sites
    1990 - FISH
    1992 - CGH (for tumors)
    2001 - CMA
  112. 112EpistasisGene interaction results in modification of phenotype
  113. 113TransferencePATIENT redirects or projects feelings they have for another person into their relationship with their counselor.
    Ex: anger, mistrust, extreme dependence
  114. 114Counter-TransferenceCOUNSELOR redirects feelings for another person into their relationship with their client.
  115. 115Autosomal Recessive InheritanceCarrier risk for unaffected full sibling of affected individual is 2/3
    Carrier risk for full sibling of parent of affected individual is 1/2
    Carrier risk for full sibling of parent of a CARRIER is 1/4.
  116. 116X-linked Recessive inheritanceIf males don't reproduce (early lethal), mutation rates are equal in males and females: carrier risk for mother is 2/3. Carrier risk for maternal grandmother and sisters is 1/3. Carrier risk for maternal aunt is 1/6.

Informações

Descrição
Genetics, Cytogenetics, and Risk Assessment review
Criado por
Farrah
Visualizações
84
Avaliação

Fale Conosco

Sobre o que é sua mensagem?

O que você acha do novo visual?

Você gostou?