Lectures are complete.

Final exam is now available Friday, May 13.

Return by Tuesday May 17.

We will begin by organizing the class, identifying who is enrolled and showing up, and describing the organization of the class. Johnston will then follow with an overview of genomics and the philosophy of genomics research.

Lecture 2011 (alt: 2 slides per page)

Strategies for mapping and sequencing genomes (prior to NextGen technology) will be described.  The need for genome maps and how they are generated will be discussed, followed by a description of how the human genome sequence was determined. After a brief discussion of the simple math of sequence coverage, I will review the technology and uses of remarkable "Next Generation" and "Next-Next Generation" DNA sequencing methods. I will discuss methods for genome assembly and annotation, focusing particularly on modern methods applicable tonextgen sequencing, and the implications for "complete" genome quality and utility for inference. This will also cover mapping technologies and how they interact with targetted sequencing (HybSeq) and experimental design.

Lecture 1; Lecture 2; Lecture 3; Reading Notes; Genome Politics; Sequence coverage math; (recording)

Historical and strategical aspects of the Human Genome Project; ESTs and STSs; human gene maps; the human genome sequence; draft vs. “finished” sequences and assemblies. Human genome structure and organization; positional biases and sequence gaps: “all regions of the human genome are not created equal”; biological, evolutionary and disease-associated insights derived from the sequence; limitations of the genome sequence. Future expectations of human genome sequencing.

Lecture (ppt); Reading;

Making sense of genomes, what they do, and how they came to be.

Since the first of these lectures was cancelled, I've put up a couple of lectures from last year. These are not perfectly in place, but something to read in the meantime.

Feb 15 lecture (recording); Lectures from last year: Intro to Biodiversity; MolEvolPhylo; Reading;

This lecture will focus on Segmental Duplications (SDs) within the genome and their role in shaping genome architecture.  SDs have played a significant role in the evolution of the primate genome and continue to have an impact on the human genome by virtue of their involvement in chromosomal rearrangements and structural variation. The processes involved in the formation of SDs and the rearrangements they mediate are an important source of human disease as well as genetic variation. SDs can give rise to duplicate genes with novel functions or can provide substrates for genome restructuring which may be key to several processes including evolution, speciation and even predisposition to common, complex diseases. Interestingly, the presence of SDs in the genome complicate proper assembly of the genome, especially using current, next-generation sequencing techniques. Will we ever have a “finished” human genome sequence?

Lecture*; (recording) Reading: Stankeiewic10; SDsEichler; Samonte02; Hurles08; Emanuel01;

This lecture focuses on the use of genome-wide technologies to identify important genomic changes related to human, great ape and primate evolution. Array-based comparative genomic hybridization (array CGH), expression studies, genome sequencing and computational genomics approaches will be discussed. The lecture will highlight advances in identifying lineage-specific genomic changes among these species, and include progress in identifying the “genes that made us human”.  Advantages and limitations of various strategies will be discussed as well as future directions and remaining challenges faced by researchers in these fields. 

Lecture; (recording)

Reading: Lineage-Specific Gene Duplication and Loss in Human and Great Ape Evolution, Fortna, et al, PLoS Biology, 2004
Jewels of our Genome: The Search for the Genomic Changes That Underlie the Evolutionarily Unique Capabilities of the Human Brain. Sikela, PLoS Genetics, 2006
Human Lineage-Specific Amplification, Selection and Neuronal Expression of DUF1220 Domains, Popesco, et al, Science, 2006
Gene Copy Number Variation Spanning 60 Million Years of Human and Primate Evolution, Dumas, et al, Genome Research, 2007
Copy number variation in human health, disease, and evolution. Zhang F, Gu  W, Hurles ME, Lupski  JR . Annu  Rev Genomics Hum Genet. 2009;10:451-81. ;

Books:
Not A Chimp: The Hunt to Find the Genes that Make Us Human, Jeremy Taylor, 2009
Before the Dawn, Nicholas Wade, 2009
Molecular Evolution, W.C. Li, 1997

Media:
Henry Stewart Talks:
Copy Number Variation in Human and Primate Evolution, J. Sikela

Transposable elements are a major component and a major force operating in eukaryotic genomes.  Their movement in evolutionary time causes variation among species and their movement in genetic time causes variation among individuals.  Three types of TEs are known: DNA transposons, and LTR and non-LTR retrotransposons.  The human genome is distinguished largely by the action of three non-LTR retrotransposons: L1, Alu and SVA.  Recent work demonstrates their underappreciated potential and importance for population level and individual variation in humans.

Lecture (recording); Reading: Lupski; Cordaux and Batzer;

Population genetics is the study of genetic differences within and among species. The aim of these two lectures is to provide a concise introduction and review of key concepts in population genetics to prepare students for later workshops and lectures on molecular evolution, targetted sequencing, GWAS, and personal genomics. Topics will include the organization of genetic information, types of polymorphisms, the causes of evolution (mutation, recombination, migration & population structure, natural selection, & genetic drift).

Lecture; recording1 ; Lecture II; recording 2; Recommended Reading: Hartl, "A Primer of Population Genetics";

This three lecture series on molecular evolutionary genomics will include an overview of statistical approaches, a lecture on applied molecular evolutionary genomics, and a lecture on phylogenetics.

Lecture 1; recording 1; Lecture 2; recording 2; (Also look for links to Jason's upcoming lectures on his blog.);

Reading:

• Zuckerkandl, E. and Pauling, L.B. (1965). “Evolutionary divergence and convergence in proteins“. In Bryson, V.and Vogel, H.J. (editors). Evolving Genes and Proteins. Academic Press, New York. pp. 97–166.
• Golding, B. and A. Dean (1998). “The structural basis for molecular adaptation.” MBE 15(4): 355-369.
• Dean, A. and B. Golding (2000).  ”Enzyme evolution explained (sort of).”  Proceedings of the Pacific Symposium on Biocomputing 5: 6-17.
• Sabeti et al. (2006).  ”Review: Positive natural selection in the human lineage.”  Science 312: 1614-1620.

Everything you still wanted to know about molecular evolutionary genomics, but were afraid to ask.

Lecture & recording (re-uploaded to fix corrupt file)

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Lecture 1 fdsf (recording) Lecture 2 slides not available (recording)

Ever since man (and woman) began ingesting foreign substances (naturally and more recently commercially drugs) variation in response to those substances has been observed.  In recent years it has become readily apparent that many positive and negative responses to medications are due to underlying metabolic pathways driven by our genetic makeup. Differences within and between ethnic groups has also been described. While many examples of gene-drug interactions have been discovered in the field of pharmacogenetics, the advent of ‘omics’ technology means that strategies can now be considered and developed to look at multiple genetic factors under a pharmacogenomic model.  This overview lecture will review pharmacogenetic and pharmacogenomic principles, describe the central role of CYP450 genetic variation, and highlight several current pharmacogenetic examples that will lay the foundation for considering the next generation of pharmacogenomic studies.

Lecture (recording); Students wishing to review more of this topics (before and/or after the class) are encouraged to read two papers by Weinshilboum RM (senior author) N Engl J Med. 2011 Mar 24;364(12):1144-53. and N Engl J Med. 2005 May 26;352(21):2211-21.

The lecture will discuss the latest information on personal genomics, an emerging field that has the potential to provide individuals with their own genome sequence quickly and inexpensively.  Topics will include the current status of this endeavor as well as genetic testing methods, and the technological, logistical and ethical challenges that are faced by such projects. Also discussed will be direct-to-consumer marketing of genomic data, the limitations of GWAS studies and missing heritability, and the inability of sequencing technologies to accurately cover and assemble complex, highly-duplicated regions of the genome. Finally issues of privacy, consent, cost and potential impact of this field on medicine and human health will be discussed.

Lecture; (recording)Suggested reading: "Here is human being: at the dawn of personal genomics" by Misha Angrist

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Lecture; (recording);Suggested reading: "Exploring expression data: identification and analysis of coexpressed genes"

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This will include identification and characterization of small RNAs, transcriptomics, and HITS_CLIP RNA methods

Both Lectures (recording 1) (recording 2) Notes, Reading: RNA-seq, Computation for CHiP and RNA-seq

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Lecture (recording)

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No Lecture Available

Gene regulation, and transcriptional regulation in particular, plays a fundamental role in many complex processes.  We present a general overview of transcriptional regulation in the context of genomic analyses.  We will give an introduction to promoter architecture and sequence elements, de novo prediction of cis-regulatory elements using various approaches, as well as a critical look at gene network structure and representation.  The lecture content should provide a brief overlook of past and previous approaches, and serves to direct further research on such methods for interested students.

Lecture & recording

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Lecture1 Lecture 2 (recording 1) (recording 2)

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Lecture & Recording