1. rare vs. common alleles
    rare mutations -> large deleterious effects; common mutations have smaller effect and milder phenotype
  2. phenotype
    phenotype = genotype + environment
  3. heritability
    the fraction of variation in phenotype that can be explained by genetic factors; NOT static - can vary within populations and over time
  4. familial clustering
    occurring in more members of a particular family than one would expect by random chance. Correlation tied to degree of relatedness?
  5. segregation analysis
    tests whether observedfamily data fit with predicted patterns; goal = determination of inheritance patterns
  6. penetrance
    refers to the proportion of people with a specific allele who exhibit clinical symptoms; not everyone with the disease phenotype have the disease genotype
  7. genetic heterogeneity
    mutations in different genes can lead to the same phenotype (opposite of variable expressivity)
  8. karyotype
    involves staining and analysis of chromosomes
  9. FISH
    fluorescence in situ hybridization; probes for specific sequences on chromosomes; useful for detecting chromosomal abnormalities or large deletions or unbalanced translocation; uses very large probes
  10. VNTR
    variable nucleotide tandem repeat (10s-100s base pair replications); can be used as a genetic marker; used in DNA 'fingerprinting'
  11. STR
    short tandem repeats (2-4 nucleotides per repeat); can be used as a genetic marker; also called microsatellites
  12. SNP
    single nucleotide polymorphism; can be used as a genetic marker
  13. Sanger sequencing
    uses fluorescently labeled dedeoxynucleotides to mark position of specific nucleotides in the genome -> sequencing (put results all together)
  14. point mutation
    single base pair change
  15. silent mutation
    no change in amino acid (but could affect splicing)
  16. missense mutation
    substitutes one amino acid for another
  17. nonsense mutation
    changes an amino acid into a premature stop codon
  18. frameshift mutation
    changes the reading frame of a gene; results in translation of different amino acids
  19. CGH
    comparative genome hybridization; involves array of probes; compares patient DNA to control DNA; able to detect deletions and duplications
  20. gene mapping
    creation of a genetic map assigning DNA fragments to chromosomes; utilizes gene linkage; utilizes genetic markers
  21. LD plot
    triangular plot that measures linkage of specific sections of DNA to each other
  22. association studies of disease
    generally = case-control studies; look at association between genetic markers (SNPs) and allele frequency in case vs. control populations; odds ratio describes strength of association
  23. types of association studies
    candidate-gene and genome-wide association study
  24. candidate gene study
    type of association study in which researchers look at the frequency of specific genes that are suspected to have biological functions related to disease
  25. GWAS
    genome-wide association study; hypothesis-free study that looks at association between genetic markers and alleles in diseased population across the genome
  26. AIS
    ancestry-informative markers; use sample SNP data to determine ancestry of study participants; method of controlling for population stratification
  27. genomic control
    method of controlling for population stratification; involves division of observed test statistic by a certain value (derived from observing other loci in the population that are not suspected to be linked with the allele in question)
  28. TDT
    transmission disequilibrium test; type of analysis for family-based association testing; number of parents who pass on suspected disease-causing allele to affected child is compared to the number of parents who pass on non-disease-causing allele to affected child
  29. Q-Q plot
    can reveal systematic error such as genotyping or population stratification error; deviation from chi-square values under the null hypothesis indicate systematic error
  30. multiple-testing adjustments
    Bonferroni test; permutation tests
  31. common disease-common variant hypothesis
    states that common traits are most likely the result of common (& therefore old) genetic variation
  32. genetic drift
    random fluctuation in allele frequencies due to chance variations; has more noticable effect in smaller populations
  33. assortative mating
    members of a population tend to have children with other members of that population
  34. positive selection
    an environmental force increases the fitness of an allele
  35. allele fitness
    refers to the ability of the allele to be passed on; does NOT necessarily mean that allele is beneficial
  36. Southern blot
    older technique that uses the principles of nucleic acid hybridization to detect and determine the size of specific fragments of DNA
  37. Northern blot
    similar to a Southern blot; detects RNA instead of DNA
  38. copy number polymorphisms
    places in the genome at which there is known to be variation in copy number between individuals
  39. synaptonemal complex
    protein structure that forms between homologous chromosomes during prophase I; mediates chromosome pairing and recombination
  40. chiasmata
    the physical bridge formed between chromosomes at the recombination site; tether homologs and maintain proper alignment; hold bivalent at meiotic plate until anaphase
  41. epigenetics
    stable and heritable mitotic and/or meiotic changes in gene expression that do not entail a change in DNA sequence
  42. constitutive vs. facultative heterochromatin
    constitutive is always inactive; facultative is active in some cells (euchromatin) and inactive in others (heterochromatin)
  43. CpG islands
    regions of DNA that contain many CG repeats; are sites of methylation
  44. X-inactivation
    immediately after fertilization - paternal X chromosome inactivated; facilitated by Xist; after inner cell mass forms all markings are erased; in each cell one of the X chromosomes (selected at random) is inactivated via Xist; some genes on the chromosome may still be active
  45. balanced X:autosome translocations
    usually the active X; become unbalanced in progeny and are inactivated; may partially inactivate autosome
  46. Angelman syndrome
    caused by paternal imprinting; paternal gene epigenetically silenced while there is a deleterious mutation on the maternal gene
  47. Prader-Willis syndrome
    caused by maternal imprinting; maternal gene epigenetically silenced while there is a deleterious mutation on the paternal gene
  48. parental disomy
    occurs when a child receives two copies of a chromosome from one parent; can lead to Prader-Willis if two maternally imprinted genes are passed on; can lead to Angelman syndrome if two paternally imprinted genes are passed on
  49. trisomy rescue
    occurs when one chromosome is lost after a nondisjunction effect; can lead to parental disomy if two remaining chromosomes are from the same parent
  50. epigenetic diseases in cis
    diseases due to epigenetic changes (inappropriately inactivated genes)
  51. epigenetic diseases in trans
    diseases due to defects in interpretation of the epigenetic code (mutation of proteins that bind methylated histones/DNA)
  52. heteroplasmy
    in mitochindria - presence of both mutant and normal DNA
  53. mitotic segregation
    in mitochondria - refers to the idea that heteroplasmic cells may produce daughter cells with higher or lower proportions of mutant DNA (random segregation)
  54. six steps in the development of cancer
    self-sustaining growth signals; insensitivity to anti-growth factors; angiogenesis; immortality; inhibition of apoptosis; metastasis & tissue invasion
  55. Vogelgram
    a diagram illustrating one theory of tumor formation; updated Vogelgram incorperates idea of driver & passenger mutations
  56. prevalence of somatically mutated cancer genes
    about 1.6% of genes show recurrent somatic mutations that appear to be indicated with cancer development; mutations in about 10% of these genes are found in the germline
  57. dominant vs. recessive cancer genes
    about 90% = dominant (oncogenes) - more constrained repertoire of mutations; 10% = recessive (tumor suppressor genes) - wide range of mutations
  58. craniosynostosis
    closing of skull sutures; involves FGFR2 gene; overactivation can lead to premature closing of sutures; alternative splicing of FGF2 in different tissues can lead to different phenotypes
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