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