Chapter 58: genetics

58.1 term

  • chromosome
  • locus (sl.) loci (pl.)
  • marker
  • allele
  • haplotype
  • genotype
  • phenotype / trait
    • endophenotype

58.2 marker

  • large marker: STRP = short tandem repeat polymorphism, STRs = short tandem repeats
    • linkage analysis
    • paternity testing
    • taxonomy
  • small marker: SNP = single-nucleotide polymorphism
    • association analysis
    • disease diagnosis
    • pharmacodynamics? drug design / pharmacogenomics = custom drug
  • RFLP = restriction fragment length polymorphism
  • platform
    • customized: MALDI-TOF MS(= mass spectrometry)
    • whole-genome gene chip
      • Affymetrix
        • Taiwan BioBank: TWB2.0
      • Illumina
    • NGS = next-generation sequencing

58.3 genome project

58.4 linkage analysis

  • Mendel 1st & 2nd laws
    • law of segregation ~ 3 : 1
    • law of assortment ~ 9 : 3 : 3 : 1
  • phenotypic model by R.A. Fisher
    • P=G+E
      • G is the genotypic component
      • E is the environmental component
    • P=G+E+GE
      • GE is the interaction between the genotypic component and environmental component
  • linkage = co-segregation = cosegregation
    • θ = recombination fraction: 1% recombination = 1 crossover per 100 meioses = 1 cM(centiMorgan) on genetic map
  • statistical hypothesis testing for in linkage mapping
    • statistical hypothesis testing for categorical trait in linkage mapping: PLA = parametric linkage analysis
      • H0: no linkage θ=0.5
      • H1: linkage θ<0.5
    • statistical hypothesis testing for quantitative trait in linkage mapping: VCLA = variance component linkage analysis
      • H0: no linkage σ2q=0
      • H1: linkage σ2q>0
  • study design
    • case control
    • trio
    • affected / discordant sib-pair
    • extended pedigree
  • data format: linkage format
    • family-based
      • PID = pedigree Id
      • IID = individual Id
      • FID = father Id
      • MID = mother Id
      • gender
      • affection
      • marker
        • M1 = marker 1
        • M2 = marker 2
  • single major locus model
    • a two-allele A and a locus influences a dichotomous trait
    • allele frequency
      • p=P(A)
      • q=P(a)=1p
    • penetrance
      • fAA=P(affectedAA)
      • fAa=P(affectedAa)=faA
      • faa=P(affectedaa)
    • disease mode of inheritance
      • dominant model
        • {fAA=1fAa=1faa=0
      • recessive model
        • {fAA=0fAa=0faa=1
      • additive model
        • {fAA=1fAa=12faa=0
      • phenocopy model
        • faa>0 perhaps due to environmental cause
      • liability model
        • e.g. fAA,fAa,faa are age-dependent

58.4.1 PLA = parametric linkage analysis

  • LOD score

58.4.2 VCLA = variance component linkage analysis

  • allele-sharing: IBS and IBD
    • IBS = identity-by-state
    • IBD = identity-by-descent

58.5 association analysis

  • LD = linkage disequilibrium
  • genotype & allele frequency
    • diallelic marker
      • pAA
      • pAa
      • paA
      • paa
      • pA
      • pa
  • HWC = Hardy-Weinberg condition
    • HWE = Hardy-Weinberg equilibrium
    • HWD = Hardy-Weinberg disequilibrium
  • gametic or haplotype frequency
    • LE = linkage equilibrium
    • LD = linkage disequilibrium