EM

BIO306 Final Exam Review Notes

Exam Information

  • Final exam: Monday, May 12th, 2:30-4:30 pm in the regular classroom.
  • 40-50% new material, rest cumulative.
  • Questions integrate old and new material.

Course Objectives

  • Fluency in genetics language and jargon.
  • Interpret genetics experiments (classic and modern).
  • Appreciate model organisms in genetics.
  • Explain Mendelian genetics principles and exceptions.
  • Describe chromosome movement during cell division and meiosis outcomes.
  • Understand linkage analysis and gene mapping in eukaryotes and prokaryotes.
  • Describe gene and chromosome structure at the molecular level.
  • Interpret mutations' effects at DNA, protein, and organismal levels.
  • Outline DNA replication, transcription, and translation.
  • Describe gene expression regulation in prokaryotes and eukaryotes.
  • Understand genetics in epigenetics, cancer, and development.

Chapter 1 Review

  • Review Chapter 1 for familiar concepts.

New Material

Diploid But Not Really

  • DNA methylation:
    • DNA methyltransferases methylate up to 10% of cytosines.
    • Maintained in somatic cells, erased in the germline.
    • Leads to decreased transcription.
    • Recruits proteins that modify histones.
    • Changes the histone code to shut off transcription of genes.
  • Epigenetics:
    • Modifications affecting gene expression without changing DNA sequence.
    • Dosage compensation:
      • Barr body, Xic.
      • Maintained in somatic cells except "escapers", not germline.
    • Genomic imprinting:
      • A few hundred genes methylated.
      • Somatic cells maintain methylation patterns.
      • Germline cells erase and re-methylate in a sex-specific way.
      • Examples: PWS vs. AS (Prader-Willi Syndrome vs. Angelman Syndrome).
  • Nutrigenetics vs. nutrigenomics
  • Impacts of epigenetics
    • Transgenerational inheritance
    • Epigenetic aging on human health
    • Integrate with gene structure, transcription, translation.

How Mutant Genes Cause Cancer

  • Cancer as a genetic disease:
    • Caused by mutations in genes that normally control cell cycle.
  • CDKs and cyclins:
    • Normal role in the progression of the cell cycle.
  • Checkpoint proteins:
    • Three checkpoints in the cell cycle and what they check.
  • Extracellular signals:
    • Control cell growth and death.
      • Growth factors, receptors, intracellular signaling proteins, TFs (transcription factors).
  • Categories of genes:
    • Genes that promote growth (protooncogenes).
    • Genes that prevent growth (tumor suppressors).
    • Genes that repair DNA damage and maintain genome integrity (tumor suppressors).
  • Types of mutations:
    • Dominant gain of function or recessive loss of function.
    • Occur in each of the three categories of genes (above) that lead to cancer.
    • Two-hit hypothesis:
      • Related to recessive mutations in tumor suppressor genes.
  • Epigenetics in cancer development
  • Progression
  • Recessive cancers in families:
    • And why these recessive cancers look dominant in a pedigree.
  • Chemotherapy and radiation treatments:
    • Based on killing actively growing cells $\rightarrow$ side effects.
    • Radioimmunotherapy, radiochemotherapy, and molecular profiling are more specific.
    • Integrate with mutation, DNA repair, cell cycle, dominant/recessive, control of gene expression in eukaryotes, and epigenetics.

Is a Leg on a Fly’s Head Still a Leg?

  • Source of maternal effect mRNAs/proteins
    • How to interpret genotypes/phenotypes
    • Their translation and localization in a gradient
    • Their function as TFs.
  • Gap genes, pair-rule genes, segment-polarity genes
    • Encode more TFs.
  • Gap and pair-rule proteins activate homeotic genes (TFs)
    • Activate genes needed to produce structures (i.e., legs, eyes, wings, etc.).
  • Homeotic genes arranged on chromosome(s)
    • In order of use in the body; conserved from flies to humans.
  • Homeodomain
    • Used by protein for binding DNA; specific to TFs involved in development.
    • Integrate with mutation, transcription/translation, eukaryotic gene regulation, TFs, genotype/phenotype.

DNA Ain’t Just in the Nucleus

  • Features of mt and cp DNA:
    • How are they similar and different from each other and genomic?
  • Uniparental inheritance
    • maternal inheritance = cytoplasmic inheritance = extranuclear inheritance.
  • Homoplasmic vs. heteroplasmic cells
  • Human mitochondrial disorders:
    • How pedigrees look, how these disorders are inherited.
    • Severity depends on the number of mutant mtDNAs and the tissues in which they are found.
  • Wear and tear theory:
    • mtDNA mutations may lead to aging (compare to telomere involvement in aging and epigenetic aging).
  • Using mtDNA sequences
    • To study origins of humans (and Y chromosome DNA too).
  • Impact of micro- and nano-plastics on mitochondrial function

Old Material

Genetics Concepts

  • Monohybrid and dihybrid crosses; true-breeding; homozygous/heterozygous; genotype and phenotype.
  • Expected genotypic and phenotypic ratios from crosses involving dominant, recessive, incompletely dominant, codominant, lethal, sex-linked, epistatic alleles.
  • Using probabilities to determine expected ratios.
  • Multiple alleles, lethal alleles, quantitative traits, penetrance, variable expressivity.
  • Principles of Segregation and Independent Assortment with respect to the process of meiosis.
  • Consequences of linkage and crossing over to expected phenotypic ratios.
  • Consequences of nondisjunction (trisomies, monosomies, etc.).
  • Sex linked, sex limited, sex influenced traits.
  • Similarities and differences between mitosis and meiosis, cell cycle, gametogenesis in humans.
  • Measuring allele frequency if the genotypes are known, or if the genotypes are not known but the phenotypes are known (using the Hardy-Weinberg equation).
  • Factors that affect allele frequencies (i.e., result in evolution/changes in allele frequency): mutation, nonrandom mating, genetic drift, gene flow, natural selection.
  • Analyzing data from test crosses to measure genetic distance based on recombination frequencies.
  • How we know that DNA is the genetic material instead of protein (interpreting experiments).

DNA Structure and Replication

  • DNA structure: deoxyribose sugar-phosphate backbone, 2 antiparallel strands held by H-bonds, purine A bonds to pyrimidine T and purine G bonds to pyrimidine C.
  • Replication: semiconservative, semidiscontinuous, bidirectional, requirement of a 3' end for DNA polymerase, new DNA made 5' to 3' off template strand.

Mutations and DNA Repair

  • Mutations: So many types (missense, nonsense, frameshift, silent; transition vs. transversion; spontaneous types vs. induced; somatic vs. germline; reversion vs. suppression; position effect, other noncoding mutations and how they affect transcription or protein production).
  • Other types of changes and their causes/consequences: inversions, deletions, duplications, translocations, transposable element insertions and their effects on phenotypes, polyploidy, aneuploidy.
  • Reduced protein function (loss of fxn): (null, hypomorphic, haploinsufficiency, dominant negative) vs. gain of fxn (hypermorphic, neomorphic, ectopic expression).
  • Know which repair mechanisms fix which types of DNA damage/lesions; mutations that persist are acted upon by forces that change allele frequencies (i.e., result in evolution).

Central Dogma

  • Central dogma (replication $\rightarrow$ transcription $\rightarrow$ translation)

Transcription and Translation

  • Txn: promoter, transcript looks like DNA coding strand with ORF, termination by hairpin formation in RNA in proks; processing, TFs in euks.
  • Genetic code universal (mostly; exceptions in mtDNA and cpDNA).
  • Translation: ribosome, tRNA, initiation (ribosome, first tRNA, mRNA come together), elongation (tRNAs come in one at a time to base pair anticodon with codon), termination (stop codon of mRNA has no corresponding tRNA).
  • ORFs: how to find them in the DNA sequence.

Gene Expression Control and Techniques

  • Negative and positive control in proks (example: lac operon); attenuation and negative control in proks (example: trp operon).
  • Control of gene expression in euks: negative and positive control at the level of txn; post-transcriptional control (alternative splicing, RNA stability, RNA interference, protein stability, protein modification).
  • Cloning DNA, restriction enzymes, gel electrophoresis, characteristics of vectors (selectable marker, origin, MCS).
  • Genomic vs. cDNA libraries: differences and purpose for each.
  • Techniques and what they show you (no questions about interpretation of results): DNA sequencing, PCR, RT-qPCR, RNA-Seq, ChIP analysis (from euk gene regulation section), molecular profiling (from cancer section).

Miscellaneous Topics

  • Markers, genetic testing/screening, gene therapy/CRISPR, cloning mammals, embryonic stem cells, eugenics, bioinformatics.
  • Chromosome structure: chromatin vs. chromosome, packaging, condensation, origins, centromeres, telomeres, euchromatin vs. heterochromatin