Genetics

From Mendel's counts to reading variation across whole genomes

About this course

Transmission genetics built on counting — segregation, linkage and mapping, gene interaction, pedigrees and mutation — then population and quantitative genetics and genome-wide association.

What you will be able to do

  • Predict offspring ratios for one and two genes and test them against the laws of chance
  • Build a linkage map from recombination frequencies
  • Calculate carrier and recurrence risks from a pedigree using Bayes' theorem
  • Apply Hardy–Weinberg and identify how selection, drift and migration break it
  • Interpret heritability estimates and genome-wide association results

What this course covers

  • Hardy-Weinberg equilibrium: derivation and meaning
  • Counting alleles and computing allele frequencies
  • Testing Hardy-Weinberg with chi-square
  • Using the square to find carrier and allele frequencies
  • Extensions: X-linkage, three alleles, and inbreeding coefficient F
  • Five forces that break Hardy-Weinberg
  • Worked MN blood group test
  • Variants: frequency, spectrum, and rarity
  • Haplotypes and linkage disequilibrium decay
  • Population stratification as a confounder
  • Genome-wide association studies: design and threshold
  • Arrays versus sequencing and the cost curve
  • Three interpretive habits for reading GWAS results
  • FTO worked example: the full GWAS calculation
  • Alleles that are not simply dominant
  • Why dominance? Flux through a halved pathway
  • One allele, multiple dominance relations
  • Penetrance and expressivity
  • ABO worked example: the O child of A×B parents
  • Dominance as a dose relation: lecture synthesis
  • Mendel's experimental design and seven ratios
  • Sampling scatter and the square-root law
  • Chi-square test and Fisher's audit
  • The F3 test and a wrong expectation
  • Segregation and independent assortment
  • Chromosome theory and Morgan's zero
  • X-linked inheritance arithmetic in people
  • The Y chromosome and sex determination
  • X-inactivation: Lyon's random, early, inherited switch
  • Patches as a count of founding cells
  • Fitting nuisance parameters in genetic counts
  • Four departures from Mendel: lecture overview
  • Mitochondrial inheritance: heteroplasmy, threshold, and bottleneck
  • Imprinting: parent of origin as part of the genotype
  • Repeat expansion and the Huntington's onset curve
  • Imprinting machinery vs. experience-based epigenetic inheritance
  • Copy number variation as a quantitative trait
  • The F3 rule: the honest boundary of transgenerational inheritance
  • Recombination frequency as genetic distance
  • The three-point test cross
  • Biological basis of crossover interference
  • Mapping functions: Haldane and Kosambi
  • The human genetic map
  • The LOD score and disease gene mapping
  • Six two-gene wirings and their F2 ratios
  • Epistasis terminology clarification
  • The complementation test
  • One gene, one enzyme
  • Consanguinity as a detector of rare recessives
  • Arithmetic behind two-gene ratio inference
  • Pathway reconstruction from multiple dihybrid ratios
  • Selection: one-line update rule
  • Kimura's neutral theory and the N-cancellation
  • Heterozygote advantage and stable equilibrium
  • Genetic drift and effective population size
  • Selection vs. drift: distinguishing the two forces
  • Founder effects, bottlenecks, and the harmonic mean
  • Migration, admixture, and FST
  • Sickle cell: fitness to map — capstone worked example
  • Dihybrid F2 count and 9:3:3:1 ratio
  • Product rule and sum rule for independent events
  • Chromosomal mechanism of independent assortment
  • Test cross as a direct gamete count
  • Cost of independence: rarest class and sample size
  • What independence buys: separability and its limits
  • Genotype verification: Mendel's F3 test
  • Three Inheritance Patterns and Pedigree Exclusions
  • Bayes' Rule Applied to Carrier Risk
  • Healthy Children as Bayesian Evidence
  • Wright's Inbreeding Coefficient F
  • Ascertainment Bias in Collected Families
  • Positive Predictive Value and Screening Arithmetic
  • Historical reconciliation of biometry and Mendelism
  • Many genes produce a normal curve
  • Partitioning phenotypic variance: VP = VA + VE
  • The breeder's equation: R = H²S
  • What heritability is not
  • Genome-wide association studies and missing heritability
  • Worked dairy-herd application of the breeder's equation
  • Lewontin's Apportionment and Edwards's Reply
  • Clusters, Gradients, and Categories
  • The Coalescent and Mitochondrial Eve
  • Segment Length as a Recombination Clock
  • Forensic DNA: The Product Rule and Its Limits
  • Identity Through Relatives' Genomes
  • Polygenic Scores: Accuracy, Portability, and Absolute Risk
  • Mutation rate: per base, per child, per division
  • Luria–Delbrück fluctuation test: design and prediction
  • Luria–Delbrück experiment: data and result
  • Replica plating: spatial proof without statistics
  • Mutation spectrum: types, hotspots, and CpG sites
  • Randomness of mutation: rate vs. direction
  • Mutation put to work: Ames test and mutation–selection balance

Syllabus

  1. Mendelian Inheritance

    1. L1 · Mendel's Experiment, Counted
    2. L2 · Two Genes, and the Arithmetic of Chance

  2. Chromosomes, Linkage and Maps

    1. L3 · Where the Genes Are
    2. L4 · Linkage, and the First Map

  3. Alleles, Interactions and Pedigrees

    1. L5 · Alleles: Dominance as a Dose
    2. L6 · Genes That Interact: Ratios as Pathways
    3. L7 · Pedigrees, and Counselling by Bayes
    4. L8 · Mutation, and How It Was Proved Random

  4. Population and Quantitative Genetics

    1. L9 · Hardy–Weinberg, and Five Ways to Break It
    2. L10 · Selection, Drift and Migration
    3. L11 · Quantitative Traits, and What Heritability Is

  5. The Genome and Beyond Mendel

    1. L12 · Reading the Genome: Variants and Association
    2. L13 · Beyond Mendel: Mitochondria, Imprinting and Repeats
    3. L14 · Ancestry, Identity, and Where This Leads