Jeff Young, Botanist youngbiol'wwu'edu x3638 Office: BI412

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Jeff Young, Botanistyoung_at_biol.wwu.edux3638Offi
ce BI412
Office Hours M, W and R 2- 3 pm by
appointment.
Arabidopsis thaliana Genome-based, molecular
study of plant physiology and environmental
responses.
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Course Goals

• Introduce Genome Scale Research,
• Develop skills in reading, understanding, and
  analyzing primary literature,
• Enjoy the enormous amount of creativity and
  genius that is being expended, right now, in the
  biological sciences.

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• Class participation general involvement in
  class,
• Quizzes a figure from a recent paper will be
  presented,
• Identify the paper,
• Answer a basic question or two pertaining to the
  findings in the figure.

Quizzes drop one low score. - and - Present a
figure in class, replace a low quiz score.
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Ill provide lots of potential papers, and help
in preparation.
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Genomics

• Genomics is the study of the structure and
  function of the Genome of an Organism,
• Structural Genomics the study of DNA sequence,
  chromatin structure, and DNA physical
  interactions in the cell,
• where are the dynamic elements located on the
  Genome, and what are they?
• Functional Genomics how does the structure of
  the genome
• Give rise to particular cell types, tissues,
  organisms?
• Respond to environmental and developmental
  requirements?
• Become diseased?
• Evolve?

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Rough Outline
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DNA Sequence Reagent for the 21st Century
Biology is in the midst of an intellectual and
experimental sea change.... ...essentially the
discipline is moving from being largely a
data-poor science to becoming a data-rich
science.
Vukmirovic and Tilghman, Nature 405, 820-822
(2000)
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Public Data Set
GBREL.TXT Genetic Sequence Data Bank
February 15 2001
NCBI-GenBank Flat File Release 122.0
Distribution Release Notes 10896781
loci, 11720120326 bases, from 10896781 reported
sequences
GBREL.TXT Genetic Sequence Data Bank
August 15 2002
NCBI-GenBank Flat File Release 131.0
Distribution Release Notes 18197119
loci, 22616937182 bases, from 18197119 reported
sequences
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Complete Genomes(Draft or Polished)

• 2001
• 9 ARCHAEAL
• 36 BACTERIAL
• 6 EUKARYAL

2002 17 ARCHAEAL 106 BACTERIAL 8 (17)
EUKARYAL
2002 202 Organelles 968 Virus/Phage viroid
s, plasmids, etc
Schizosaccharomyces pombe (Feb., 2002) Fugu
rubripes (Aug., 2002) Yersinia pestis (Aug.,
2002)
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Range?

• 100s of genome projects in progress, both
  public
• and private.

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Why?
2 trillion /year 60,000 genes
0.5 trillion /year 35,000 genes
Animals
Plants
Bacteria
0.1 trillion /year 15,000 genes
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Scientific Motivation?
Shared common set of highly homologous genes!
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16 FEBRUARY 2001 VOL 291 SCIENCE, pp.
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Scientific Motivations?
Shared common set of highly homologous genes!
Relatively few parts!
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http//www.bmm.icnet.uk/3dgenomics/
738 SCOP (Structural Classification of Proteins)
domains.
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Scientific Motivations?
Shared common set of highly homologous genes!
Relatively few parts!
Diversity is in the details!
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http//www.ebi.ac.uk/proteome/
Saccharomyces cerevisiae vs. Schizosaccharomyces
pombe (Feb. 21, 2002)
Nature 2002 Feb 21415(6874)
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Genome Project Goals

• Establish an integrated WEB-based database and
  research interface,
• Assemble physical and genetic maps,
• Generate genomic and expressed (mRNA) gene
  sequences,
• Identify and annotate the complete set of genes
  encoded within a genome,
• Compile atlases of gene expression,
• Accumulate functional data (functional genomics
  reverse genetics, proteomics, structural
  genomics, etc),
• Characterize sequence diversity between and among
  organisms.

• Establish an integrated WEB-based database and
  research interface,
• Assemble physical and genetic maps,
• Generate genomic and expressed (mRNA) gene
  sequences,
• Identify and annotate the complete set of genes
  encoded within a genome,
• Compile atlases of gene expression,
• Accumulate functional data (functional genomics
  reverse genetics, proteomics, structural
  genomics, etc),
• Characterize sequence diversity between and among
  organisms.

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Web-based Database and Research Interfaces
http//www.ncbi.nlm.nih.gov/About/tools/index.html
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Literature (PubMed)
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Literature (OMIM)
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Literature (PROW)
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Genome Project Goals

• Establish an integrated WEB-based database and
  research interface,
• Assemble physical and genetic maps,
• Generate genomic and expressed (mRNA) gene
  sequences,
• Identify and annotate the complete set of genes
  encoded within a genome,
• Compile atlases of gene expression,
• Accumulate functional data (functional genomics
  reverse genetics, proteomics, etc),
• Characterize sequence diversity between and among
  organisms.

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Functional Genomics
Hieter P and Boguski M. Science 278, 601-02.

• ...Functional genomics...is characterized by
  high throughput or large-scale experimental
  methodologies combined with statistical and
  computational analysis of the results.
• ...the fundamental strategy in a functional
  genomics approach is to expand the scope of
  biological investigation from studying single
  genes or proteins to studying all genes or
  proteins at once in a systematic fashion.

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Functional Genomics
Hieter P and Boguski M. Science 278, 601-02.

• ...Computational biology...will perform a
  critical and expanding role in this area whereas
  structural genomics has been characterized by
  data management, functional genomics will be
  characterized by mining the data sets for
  particularly valuable information.
• ...functional genomics promises to rapidly
  narrow the gap between sequence and function and
  to yield new insights into the behavior of
  biological systems."

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http//www.nsf.gov/pubs/2001/nsf01162/nsf01162.htm
l
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10 Year Schedule
1- to 3-Year Goals
Develop essential genetic tools, including the
following
- comprehensive sets of sequence-indexed mutants,
accessible via database search, - whole-genome
mapping and gene expression DNA chips, - facile
conditional gene expression systems.
- Produce antibodies against, or epitope tags on,
all deduced proteins. - Describe global protein
profiles at organ, cellular, and subcellular
levels under various environmental conditions.
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10 Year Schedule
3- to 6-Year Goals
- Create a complete library of full-length
cDNAs. - Construct defined deletions of linked,
duplicated genes. - Develop methods for directed
mutations and site-specific recombination. -
Describe global mRNA expression profiles at
organ, cellular, and subcellular levels under
various environmental conditions. - Develop
global understanding of post-translational
modification. - Undertake global metabolic
profiling at organ, cellular, and sub-cellular
levels under various environmental conditions.
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10 Year Schedule
10-Year Goals
- Artificial chromosomes. - Identify cis
regulatory sequences of all genes. - Identify
regulatory circuits controlled by each
transcription factor. - Determine biochemical
function for every protein. - Describe
three-dimensional structures of members of every
plant-specific protein family. - Undertake
systems analysis of the uptake, transport, and
storage of ions and metabolites. - Describe
globally protein-protein, protein-nucleic acid,
and protein-other interactions at organ,
cellular, and subcellular levels under various
environmental conditions. - Survey genomic
sequencing, and deep EST sampling from
phylogenetic node species. - Define a predictive
basis for conservation versus diversification of
gene function. - Compare genomic sequences within
species.
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Post/Pre...Genomics

• Pre Essentially the enormous complexity of a
  living organism overwhelmed existing analytical
  tools, and real progress came from approaches
  that ignored the complexity and focused on the
  component parts.
• Post In the short term, the goal is to assign
  some element of function to each of the genes in
  an organism, and to do this with high-throughput,
  systematic approaches.

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For Friday