Transcript Introduction to Genetics and Genomics

Anouncements
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Lab tonight: 1245 SC
Bring own laptop/computer is welcome
CSS accounts
Questions about Perl install (which is
perfect for Lab)
• Lectures have been mapped out further
on web
• Next paper (probably tonight).
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Review Central Dogma
• Transcription
• Translation
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Summary of Paper
• Where are we in Genomics?
• J.F. Hocquette
• Journal of Physiology and
Pharmacology, 2005, 56, Supp 3, 37-70
• Herbivore Research Unit
• Saint-Genes Champanelle, France
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Genomics
• Classically divided into two basic areas
– structural genomics -- characterization of the
physical nature of whole genomes
– functional genomics -- the characterization of
overall patterns of genes expression
• Two "new paradigms"
– view is more global due to the development of
high-throughput techniques
– development of bioinformatics -- (needs the use of
computers to manage biological information) -direct consequence of more information available
derived from genomics studies.
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Genomes
• 240 genomes sequenced
• 1000 in progress (with links in paper)
• What are all of the genes -- not completely
solved (ex. yeast ORFs still being corrected)
• ENCyclopedia Of DNA Elements (ENCODE) -develop techniques to identify all protein-coding
genes, non-protein coding genes, and any other
DNA elements
• www.genome.gov/ENCODE
• "Most of our genome is 'silent'
• "It was also observed in humans that introns are,
on average, 14 times shorter in highly expressed
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than in low expressed genes." Why?
Misc.
• "It was recently demonstrated that the spatial
organization of chromosomes is tissuespecific."
• polymorphism -- DNA sequence differences
between organisms, species, or individuals
(of same species)
• pharmacogenetics -- inherited differences in
DNA which affects drug metabolism)
• nutrigenetics -- inherited differences in DNA
which affects diet response
• pharmacogenomics -- study of the genes that
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determin drug behavior and response
Misc
• SNPs: www.ncbi.nlm.nih.gove/SNP
• Chips for genotyping with 10,000 SNPs
• www.moltools.org -- increase
genotyping throughput, precision, and
improve cost (European)
• www.gnome.gov/HapMap
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Epigenetics
• -- DNA sequence is unlikely to be the
exclusive source of heritable information
– methylation and/or histone arrangement
– The epignome
– www.epignome.noe.net
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RNA studies
• Presence of any RNA molecule implies that
the underlying gene is expressed.
• techniques: differential display, SAGE, cDNA
arrays, oligonucleotide arrays -- what about
EST sequencing????
• transcriptomics
• Limitations of arrays -- variability arises from
a great number of sequential steps from array
preparation
• Application -- molecular profiles correlate to
disease states -- they can be used as
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diagnostic tools
Protein Studies
• "more than 90% of the genome serves no
known purpose???"
• 30,000 genes produce about 1 million
proteins
• 10% of the genes have been suggested to
encode more than 90% of the proteins
• Protein complexity -- comes from:
– 40% of human/mouse genes are alternatively
spliced
– multiple transcription start sites
– polyadenlylation and pre-mRNA editing
– posttranslational protein modification
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Proteins cont
• www.interaction-proteome.org
• www.functionalgenomics.org.uk/section
s/resources/protein_arrays.hml
• "…some authors claim the human
proteome will continue to lie beyond
detection threshold of current analytical
procedures."
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Misc
• 20,000 knockout strains of yeast have
been created
• single-gene knockout mutants are
commercially available.
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Systematic Approaches
• "biological systems have been broken into
simple units and analysed independently."
• Not a criticism -- just all that was possible
until recently
• Phenotype of whole organism "phenome"
• Figure -- not terribly insightful
• "interpretation of genomic studies in
combination with phenotypic data" -challenge of next decade
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Systematic approaches cont
• generic model organism database
• www.gmod.org
• distributed annotation system DAS
• biodas.org -- allows for integration of different
databases across the world
• Systems biology -- "This approach has thus
the potential to reveal unexpected properties
of biological systems not accessible by
analysing individual molecule classes or
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separate biological processes."
Bioinformatics and In Silico Biology
• Information that needs to be analyzed:
– 1) genome, DNA, and protein sequences, 2)
nucleic acid and protein structures, 3) gene and
protein expression data, 4) molecule interactions,
and 5) the interaction between integrative biology,
systems biology, and literature
• BioSPICE -- simulation tools for intra-cellular
processes
• what is "in silico" biology?
• "The next level of complexity is network
analysis to detect novel interactions and
regulatory connections between genes and
groups of genes, in order to understand
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biological systems."
New Journals
• PLoS Computational Biology -- 2005
• Claim to fame -- open source
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Finally -- Concerns about
Biotech
• food safety related to human health
(especially in Europe)
• detrimental environmental impact and loss of
biodiversity
• dissemination of genetically-modified
organisms
• economic and regulatory concerns over
control of biotech by private companies
• lack of transparency in food science
• ethical concerns about animal welfare
• use of gene-related biotech in medical
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science