(completed lectures are below)

April 20

Immunogenomics

Lecture PDF . Reading: Immunocentric view of human genome; shared genetics of immune diseases; how did our immune system evolve?;HLA and infectious diseases; genetics and immunity.

April 27, April 29, May 4

Human Genome Evolution and Structural Variation I, I, & III

Recommended 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 et al Annu Rev Genomics Hum Genet.  2009;10:451-81. 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. Henry Stewart Talks: Copy Number Variation in Human and Primate Evolution, J. Sikela

May 6 & 11

Functional Genomics I & II

First Lecture PDF. Second Lecture PDF. Reading zip.

May 13

Social Impact of Genomics

The lecture focuses on the effects of genomics in medicine, human self-understanding, genomic engineering, law and social control, and human enhancement. We also consider the role and responsibility that those who understand the technology have to help the rest of society anticipate and respond to societal impacts. Lecture PDF. Extra Reading: Resolving Individuals Contributing Trace Amounts of DNA to Highly Complex Mixtures Using High-Density SNP Genotyping Microarrays
http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000167

Week of May 17: FINAL (take home)

January 26

Pollock/Johnston

√ Organize Class, Overview of Genomics

January 28

February 2

√Mapping and Sequencing I

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.

Lecture. Reading: Olson1, Olson2, HumanConflict. Further references. Genome mapping math notes.

February 4

√Mapping and Sequencing II

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.

Lecture. Reading: Shendure, PacBio.

February 9

√Sequence Search and Databases

According to the 2010 Nucleic Acids Research databases issue, peer review identifies 1230 molecular biology databases of value to biomedical research.  In this lecture, we will take a quick tour of this rich landscape, touching on the immense variety of information available and how to find it.   Since naming of genes and gene products is ambiguous (and sometimes controversial), the best way to find information is often to use sequence information rather than names.   Available databases range over evolutionary, genomic, structural, expression and functional information.  Much of this information is centralized in the extraordinarily rich information catalogued at the National Library of Medicine, although there are significant resources outside of NLM as well.

Lecture PDF. Reading: Nucleic Acids Research online Molecular Biology Database Collection, NCBI Entrez User Education pages.

Homework: Pick a favorite gene (or, if you don’t know any, how about looking up one of my favorites, PPAR-Delta) and gather information about it from at least five distinct resources.

February 11

√The Human Genome

Historical and strategical aspects of the Human Genome Project; ESTs and STSs; 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.

Notes. Reading.

February 16

√Comparative Vertebrate Genomics

Important insight into the evolution and functional significance of genomic sequences has benefited greatly from comparative genomics. In this section we will: address the lack of correlation between genome size and organismal complexity (C-value paradox) – discuss synteny and the importance of alignments in comparative genomics – address gene duplication and orthologs vs. paralogs – and identification of conserved non-coding elements (CNEs). Incorporating these concepts, we will tour prominent literature examples of comparative genomic analyses to demonstrate major concepts of how genomes change through time, and how genomic characteristics have changed in ancestral lineages leading to humans.

Lecture PDF. Reading.

February 18

√Genome Annotation and Assembly

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 PDF. Reading: Abyss, Velvet, Panda.

Februrary 23

√Transposable Elements

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.

Lecture PDF. Reading.

February 25

√Genome Architecture, Segmental Duplication and Rearrangement

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. These rearrangements are an important source of human disease and variation. SDs also provide substrates for the formation of new genes which can have  potential significance on evolution and speciation . Furthermore, the presence of SDs in the genome complicate proper assembly of the genome, especially using current, next-generation sequencing techniques.

Lecture PDF. Reading: Eichler, Saitta.

March 2

√Transcriptomics I

This lecture focuses on the use of array-based technologies to analyze: Gene Expression, the regulation of transcription (ChIP on Chip and microRNA), Comparing Genomes ((SNP arrays), and “putting it all together”.  Lung Cancer investigative efforts are highlighted for many of the examples of how microarrays are currently used. Notes. Lecture PDF. References.

March 4

√Transcriptomics II: Landscape of Bioinformatics Software for High-throughput Biological Data

Here, we explore the landscape of Bioinformatics software in the post-genomic era. Bioinformaticians have built many flavor of software to suite all computer skill levels. High-throughput analysis software began with Microarray analysis, and quickly evolved to handle Next Generation Sequencing dataset. A bird's-eye view of these landscape will better prepare you for your future analysis needs. Lecture PDF. Reccomended Reading: BrB and DAVID. Background reference list for those who are further interested.

March 9

√Transcription Factor Binding

This lecture will review transcription regulation and the role of
transcription factor binding sites (TFBS) in this process. The problem
of identifying the locations of TFBS will be presented along with a
summary of resources. Low and high-throughput experimental methods for TFBS detection will be reviewed. The lecture will end with an introduction to computational methods for TFBS prediction.

Lecture PDF. Reading: Bulyk (2006); What are DNA sequence motifs? D'haeseleer (2006); How does DNA sequence motif discovery work? D'haeseleer (2006)

March 11

√High Throughput RNA Sequencing

This will include identification and characterization of small RNAs, transcriptomics, and HITS_CLIP RNA methods. Lecture PDF. Reading: RNAseq review; RNAseq Calcs.

Spring Break March 15-19

March 23

√Proteomics

This lecture will provide an overview of proteomics. The focus will be on mass spectrometry methods for protein identification, characterization of post-translational modifications, quantification and gaining structural insight. Practical considerations will be given and examples of the various methods from current literature for further reading. Finally, a targeted proteomics approach will be described. Lecture PDF.

March 25

Please download, and please let David Pollock know that you are planning to turn in a midterm. Please contact David Pollock immediately if you have any questions or notice anything confusing or wrong. Also, look here regularly for corrections or clarifications. I will also answer any questions I can at class today. It is due in one week (April 1, 2010).

March 30

√Molecular Evolution and Phylogenetic Trees

Just as molecular evolution is at the scientific core of molecular biology and genetics, evolutionary genomics is at the core of genomics. The lecture will cover the basics of how we study where genes and genomes come from, and how and why they came to exist. What restrictions are placed on sequences as they change over time? How are molecular innovations created? What did ancestral molecules look like? Lecture PDF. Reading: “Evolution of Dim-Light and Color Vision Pigments” Yokoyama, Ann Rev Gen 2008 9:259-282; "Mechanistic Approaches to the Study of Evolution: The Functional Synthesis”, Dean and Thornton, Nat Rev 2007 675-688 .

April 1

Midterm is due 5:00 pm today

SNPs, Haplotypes, Linkage Disequilibrium and Targetted Sequencing. No abstract provided.

Lecture PDF.

April 6

Genome-Wide Association Studies. No abstract provided.

Abstract. Notes. Lecture PDF.

April 8

PharmacoGenomics/PharmacoGenetics

The Pharmacogenomics lecture will briefly review some history about the field and distinguish pharmacogenetics from pharmacogenomics. Phase I and Phase II drug metabolism will be discussed as they relate to pharmacogenomics. The human CYP450 enzyme system and other key pharmacogenetic examples will be presented to illustrate the application of pharmacogenetic/omics to clinical medicine. Notes. Lecture PDF. Reading.

April 13

Metagenomics

Metagenomics, the study of mixtures of genomes extracted directly from environmental or clinical samples provides access to phylogenetic and functional diversity without the need for cultivation.  The ability to study mixtures of organisms also better reflects the natural state of the microbial world.   Application of metagenomics in natural and clinical settings illuminates new features of the microbial world that were not known from study of single organisms.
Lecture PDF. No Reading assigned.

April 15

Schwartz

Epigenomics

No abstract or lecture notes provided. Reading: Cancer epigenetics; Colon Cancer Metabolome.

April 22

NO LECTURE TODAY