Time: Tuesdays 4:30-6:20 pm

Dates: 29 Sep - 12 Dec. 2003

Location: Room 389 Neuberger Hall

Instructor: Dr. Susan Masta

Office: M103 (inside Room 103), Science Building 1

Email: smasta@pdx.edu

Phone: 725-8505

Office Hours: Mondays 4:00 - 5:00 pm, and by appointment

Course Description: The completion of the sequencing of the human genome was announced this spring. But how do we interpret what the sequence means? This course will introduce you to the approaches and techniques used to sequence and analyze genomes. We will examine how comparing genomes within and between species is vital to understanding and interpreting genomic data. The course will combine discussion of current literature with hands-on computer analyses to familiarize you with the burgeoning field of comparative genomics.

Course Objectives: You will become familiar with:

Where to find genomic information and resources

How to find and annotate genes

How to make phylogenomic comparisons

What we have learned from comparing genomic data

The history of the Human Genome Project: who, what, when, where, and how

What we can do, can't do, and may soon be able to do, with genomic data

Assignments: There will be weekly assigned readings, that will be available via WebCT . You will need to prepare two questions or comments based on these readings in advance of each class, and we will begin our discussions by each presenting our questions. All students will be expected to participate in the classroom discussions. For one of the classes, each student will have an individual research/reading assignment they will need to summarize for the class. There will be computer-based assignments to familiarize you with some of the databases and analyses used in genomics. These will be explained and illustrated during class. Graduate students will prepare for and lead a portion of one of the classes. There will be no quizzes, tests, or final exam.

Grading: Grades will be based upon attendance, class participation, the quality of the preparation for the discussion section the student helps lead, and the computer assignments.

What is "comparative genomics"?

Timeline of comparative genomics developments

Overview of syllabus, expectations

Databases for genomics resources: NCBI

Pennisi, E. 2001. The Human Genome. Science 291:1177-1180.

Roberts, L. 2001. Controversial from the start. Science 291:1182-1188.

Baltimore, D. 2001. Our genome unveiled. Nature 409:814-816.

Wade, N. 2003. Scientists say human genome is complete. The New York Times.

7 October: The Human Genome Project.

Discussion of above papers:

The history of the Human Genome Project. Why, when, who and how.

The public versus the private sector

Why sequence the human genome?

Ethical and societal issues: Iceland's Genomic Database as a case study

Assigned reading: read pages 863-875, beginning with 'Hierarchical shotgun sequencing'

Discussion of assigned reading on hierarchical shotgun sequencing

Large-scale sequencing methods: cloning and BAC library creation

Sequence quality scoring, vector screening (phred)

Sequence assembly into contigs and skeleton frameworks (phrap)

Introduction to evolutionary thinking:

Phylogenetic analyses: tree terminology and parsimony

Concept of homology

Computer lab (322 Cramer Hall)

Sequence alignment: global versus local

Databases and tools for annotating sequence (FASTA, BLAST)

Modifying search strategies; searching different databases

Inferring gene function from relatedness to other genes

Finding Open Reading Frames (ORFs)

distinguishing introns from diverged exons

Computer lab (322 Cramer Hall)

CLUSTALX introduction

Sequence alignment based on predicted secondary and tertiary structures

tRNA folding introduction (tRNAscan)

Mapping to known regions

Other gene finding methods

Phylogenetic analyses: introduction to programs

Discussion of mitochondrial genome paper

Genome size, content, and gene order

The minimal genome

Assigned reading: Salzberg et al, 2001. Microbial genes in the human genome: lateral transfer or gene loss? Science 292: 1903-1906.

Student summaries of bacterial genomes

Phylogenetic analyses to determine relationships and interpret character evolution

Class discussion of "Microbial genes in the human genome: lateral transfer or gene loss?"

Assigned reading: parts of Waterston et al. 2002. Initial sequencing and comparative analysis of the mouse genome. Nature 420:520-562.

Vertebrate evolution based on genome comparisons

Class discussion of the mouse genome paper

Graduate student presentation: Human and chimpanzee genome comparisons

Assigned reading: Rokas, A., B. L. Williams, N. King, and S. B. Carroll. 2003. Genome-scale approaches to resolving incongruence in molecular phylogenies. Nature 425:798-804.

In-class assembly of a mitochondrial genome

Class discussion of "Genome-scale approaches to … phylogenies".

Discussion of the future of genomics