BIO5285: Fundamentals of Mammalian Genetics.

Commences on September 1st 2009.

Course organizer: M. Lovett (Lovett@genetics.wustl.edu). Teaching Assistant Nicole Renaud (renaud.nicole@wustl.edu))

This course aims to provide both biologists and those with mathematical backgrounds with a basis in mammalian genetics. This is a required first year course for the Human and Statistical Genetics (HSG) Ph.D. program.

The assigned textbook for this course is Human Molecular Genetics Third Edition by T. Strachan and A.P. Read. Garland Science 2004. It should be noted that not all of the course material is covered by this textbook.

The final grade assessment on this course is based upon the following breakdown:

All of the lectures will be available to you as Powerpoint presentations for download at http://hg.wustl.edu/info/fmg2009/index.html.
In most cases homework assignments and pdfs will also be available at this same URL.

A note on plagiarism. Plagiarism will be taken very seriously. At the very least, if you plagiarize, you will receive a failing grade and in severe cases you will be reported to the dean's office for appropriate further action. In written assignments do not copy reference material verbatim and be sure to cite all sources used.

Lecture 1 Introduction
Bowcock September 1st: History of Human Genetics. Early cytogenetics and linkage studies, HapMap, Introduction to Mendelian genetics and positional cloning. DNA structure, polarity, DNA replication, transcription, translation, histone organization, mitosis, meiosis.

Lecture 2 and 3 Genes and Chromatin I & II
Lovett September 3rd & 8th: Euchromatin, heterochromatin, centromeres, telomeres, artificial chromosomes, gene distribution, mRNA structure and processing, pseudogenes, synteny, noncoding RNAs, microRNAs, rRNA, repetitive elements, large scale genomic polymorphisms. Gene regulation, splicing, RNA editing, Pol I, II and III transcripts, cis-acting control elements, conserved elements, ultra-conserved elements transcription factors.

Lectures 4 and 5 Molecular Pathology of Disease I & II
Gurnett September 10th & 15th: Numerical chromosome abnormalities, aneuploidy, non-disjunction, translocations, structural/copy number change, non-allelic homologous recombination, sister chromatid exchange, gene conversion, segmental aneuploidy, contiguous gene deletion syndromes, L1 insertions. Mutation (frequency, location and types) nonsense mediated decay, splicing and splicing defects, loss versus gain of function mutations, dominant negative effects, DNA repair.

Lecture 6 Genome Methods I
Lovett September 17th: Comparative genomics, physical maps, molecular cytogenetics, methods for expression profiling, genotyping, copy number detection and resequencing. Next generation sequencing methods. Targeted medical resequencing. Comparative genomic hybridization, genomic representations, genomic tools for exploring epigenetic modifications.

Lecture 7 Introduction to Human Population Genetics
Templeton September 22nd: Phenotypic variation in natural populations, Hardy Weinberg, mutation, genetic drift, recombination, selection, population structure, molecular evolution.

Lecture 8 Genome Methods II
Lovett September 24th: Comparative genomics, physical maps, molecular cytogenetics, methods for expression profiling, genotyping, copy number detection and resequencing. Next generation sequencing methods. Targeted medical resequencing. Comparative genomic hybridization, genomic representations, genomic tools for exploring epigenetic modifications.

Lecture 9 Mendelian Traits
Gurnett September 29th: Genetic mapping, marker informativity, recombinants, LOD scores, parametric vs nonparametric analyses, genetic heterogeneity, genome wide scans, haplotype analysis, homozygosity mapping, admixture mapping.

Lecture 10 Human biochemical genetics/metabolic genetics
Kozel October 1st: Clinical presentation, molecular mechanisms, diagnostic strategies, treatment options for the major classes of inborn errors of metabolism.

Lecture 11 Mitochondrial genetics
Kozel October 6th: Structure of the mitochondrion and its genome, homoplasmy and heteroplasmy, genetic bottlenecks, reactive oxygen species, organ systems and characteristics of mitochondrial disease, mitochondrial migrations.

October 8th
Review and discussion prior to midterm.

Lecture 12 Epigenetic Mechanisms I
Lovett October 13th: Mechanisms and regulation of dosage compensation in mammals and model organisms.

Midterm October 15th

Lecture 13 Epigenetic Mechanisms II
Urban October 20th: Genome wide epigenetic alterations, DNA methylation and its regulation, histone modifications, RNAi, polycomb and trithorax proteins, imprinting.

Lecture 14 Epigenetic and Disease
Urban October 22nd: Uniparental disomy, Prader-Willi, Beckwith-Wiedermann, Silver Russell, Disorders affecting chromatin structure in trans, disorders affecting chromatin structure in cis, Fragile X, epigenetics in common diseases.

Lecture 15 Cancer genetics
Tomasson October 27th: Evolution of cancer, characteristics and examples of mutated oncogenes, tumor suppressors and DNA repair genes in cancers, mutation/rearrangement detection systems, loss of heterozygosity, epigenetic silencing, translocations, genomic instability and cancer.

Lecture 16 Discussion I
October 29th

Lecture 17 Complex Disease Genetics
Bowcock: November 3rd: Common disease: common variant hypothesis, lambda S, linkage disequilibrium, case control and family-based association mapping.

Lectures 18 and 19 Neurodegenerative Disease I & II
Goate November 5th & November 10th: Diseases of unstable repeat expansion, inheritance patterns and characteristics, age of onset and numbers of repeats, anticipation, genetic modifiers, animal models, genetic testing, therapeutic development. Alzheimer's disease, animal models, the amyloid hypothesis, frontotemporal dementias, prion diseases, rare dementias.

Lecture 20 Discussion II
November 12th

Lecture 21 Psychiatric Genetics I
Saccone November 17th: Heritability and characteristics of major psychiatric diseases, diagnostic criteria, endophenotypes, the impact of diagnostic error, animal models of behavioral/psychiatric disease.

Lecture 22 Psychiatric Genetics II
Heath November 19th:

Lectures 23, 24 and 25 Murine Genetics I, II & III
Lovett November 24th, Jay December 1st and December 3rd: Transgenics, knockouts, conditionals, ENU and insertional mutagenesis screens, identifying modifier genes, haplotype-based genetic analysis, mouse strains, congenics, recombinant inbreds, advanced intercrosses, quantitative trait loci mapping. Embryonic stem cells.

Lecture 26 Discussion IV
December 8th

Final Exam December 15th

Take Home Exam is due by December 18th