MCB 316: Genetics and Disease
2012
Mary A. Schuler
Topics:
Basic cell structure (compare and contrast bacteria, plant cells, and animal cells; internal
structures including genomes)
General discussions on meiosis and mitosis, reproduction in relation to the life cycles of
vertebrates, budding and fission yeast, Arabidopsis, Zea mays, and Drosophila
Basic Mendelian genetics (monohybrid/dihybrid crosses, inheritance patterns in model
organisms with varying numbers of genes determining a trait, pedigree analysis in
humans)
Non-Mendelian inheritance patterns (incomplete dominance, codominance, penetrance,
epistasis/gene interaction, lethals, sex-linked, multiple alleles and gene complementation)
Mutation and the various affects on protein expression and phenotype (dominant vs.
recessive, gain-of-function vs. loss-of-function, dominant negatives)
Sex-linked inheritance patterns and disease examples (hemophilia, color-blindness,
Fragile-X (introduce karyotype and PCR-based testing of disease))
Molecular basis of sex-determination in mammals and Drosophila
Dosage compensation of sex-linked genes in mammals and Drosophila (Barr bodies and
mosaicism)
Organismal ploidy (discussion on hybrid vigor esp. in relation to plants, affects of ploidy
on meiosis and fertility, tissue-specific ploidy esp. Drosophila polytene chromosomes
(introduce chromosome spreads and in situ hybridizations))
Chromosome organization (centromeric structures, chromosome rearrangements, nondisjunction/aneuploidy, chromosomal fusions, phenotypic results of these events)
Linkage analysis, crossing over, measuring map distances on chromosomes (examples
mostly in plants, Drosophila and lastly yeast, effects of gene rearrangements on meiosis
(gene loss, balancer chromosomes in Drosophila))
Localizing mutations on chromosomes (use of specific balancer stocks in Drosophila to
define chromosome carrying mutation, use of deletion and duplication strains in
Drosophila to sublocalize gene on chromosome, in situ hybridization techniques, use of
pedigree and RFLP analysis in humans, somatic-cell hybridization technique, use of
chromosome rearrangements to map Duchenne muscular dystrophy and other X-linked
genes)
DNA and chromatin (methods identifying DNA as genetic component in most organisms
and RNA as genetic component in some viruses, DNA organization (base-pairing
interactions, helical forms, methods demonstrating supercoiling), classes of chromosomal
proteins, centromeres, kinetichores and telomere organization in yeast, defining genome
complexity with Cot curves, in situ hybridization to localize repeats in chromosomal
sequences)
DNA replication (leading and lagging strand synthesis, pulse and pulse-chase methods
measuring DNA and RNA synthesis, methods for sizing nucleic acids and separating
cellular components (density vs. velocity gradients, differential centrifugation), origins of
replication, DNA polymerases and different activities, error rates and DNA mismatch
repair, unique aspects of eukaryotic replication (cyclins, nucleosomes, telomeres))
RNA synthesis and processing (various levels of gene expression from nuclear genes,
types of RNA involved in synthesis of proteins including mRNA, tRNA, rRNA and
snRNA, methods defining rate of RNA synthesis and half-life (pulse and pulse-chase),
mechanism of RNA synthesis and types of polymerases, basal promoter structures and
basal transcription factors, RNA editing of mitochondrial transcripts, nuclear pre-mRNA
capping, polyadenylation, and splicing, comparison of introns between mammals and
non-vertebrates, alternative splicing (vertebrate troponin T and NCAM genes, Drosophila
sex determination genes))
Translation (comparison of RNA and proteins in bacterial vs. eukaryotic ribosomes,
properties of the genetic code (wobble codon, relationship to nucleotide mutations)
Mutations (types including silent, missense, etc., tRNA/suppressor mutation, somatic vs.
germinal, isoalleles, null alleles, transitions/transversions, conditional alleles, examples
of diseases associated with gene mutations (sickle cell, thalessemias, phenylketonuria,
etc.), mechanisms causing natural and induced mutations (tautomeric shifts, chemicals,
radiation, transposons)
Transposons (characteristics using examples from bacteria, maize and Drosophila
including Ac/Ds elements, P-elements, mariner elements, retrotransposons, effects of
transposon mutations on genomes)
Molecular genetic techniques needed for gene characterizations (restriction enzymes,
plasmid vectors, phage vectors, phagemid vectors, bacterial artificial chromosomes, yeast
artificial chromosomes, cDNA libraries, genomic DNA libraries, screening techniques
(plaque hybridization, expression and complementation screening), Southern analysis and
in situ hybridizations to define gene copy number, use of RFLP and Southern analysis to
identify mutated genes, chain-termination sequencing, DNA fingerprint analysis)
Methods for defining levels of gene expression (Northern Blotting analysis, RT-PCR
analysis, EST and cDNA cloning, dot blotting, oligonucleotide arrays, microarrays)
Gene mapping (genetic maps, cytological maps, physical maps, RFLP mapping, cloning
mutant genes with no known cDNA (chromosome walking, chromosome jumping),
radiation hybrid mapping, cloning, mapping of Huntington’s disease, trinucleotide repeat
disorders, cystic fibrosis and sickle cell anemia disease genes, human gene therapy
techniques including gene-product therapy and somatic and germline gene therapy)
Creation of transgenic organisms (use of gene injection, retroviral infection and
embryonic stem cells in vertebrate systems, use of T-DNA and Agrobacterium in plants,
comparisons of different methods of protein production from different sources)
Regulation of eukaryotic gene expression (examples of transcriptional, posttranscriptional, translational regulation, spatial and temporal regulation, factor-dependent
regulation, steroid and peptide hormone regulation, enhancers and transcription factor
classes)
Animal development (Drosophila morphogenesis from embryo to adult, sex
determination pathway, maternal vs. zygotic effect genes, dorsal-ventral axis, anteriorposterior axis, body segmentation, organ formation, comparison to colinearity in
vertebrate development)
Genetic basis of cancer (cell cycle regulation and checkpoint control, tumor suppressors,
oncogenes, two-hit hypothesis, genetic predispositions)
Special paper topics (Huntington’s disease mechanisms detected, genomics for medicine,
genomics approaches to diagnosing cancer, therapeutic siRNAs, pharmaceutical
production in plants)