Genes and Genomes

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• Genes and Genomes

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Raw Genome Data
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Celera says that there are only 30,000 genes

• Affymetrix 60,000 human genes on GeneChips?
• Incyte over 120,000 genes?
• GenBank 49,000 gene coding sequences?
• UniGene gt 89,000 clusters of unique ESTs?

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What are genes?
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Eukaryotic Genomes
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Dogma I
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Dogma II
The "one gene one protein hypothesis predates
the description of the chemical structure of DNA
by Watson and Crick 1953 and even the
identification of DNA as the molecule of
inheritance.
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Exon skipping mutations in A. thaliana splicing
in multi-intron pre-mRNA may be affected by other
introns in transcript
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Eukaryotic Genes
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A Dynamic Concept

• Introns/exons
• Postransriptional modifications
• Alternative splicing
• Differential expression
• Genes-in-genes
• Genes-ad-genes
• Postranslational modifications
• Multi-subunit proteins

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Maybe

• A
• One Gene - One Transcript
• Dogma

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Current consensus

• 15,000 known genes (similarity to previously
  isolated genes and expressed sequences from a
  large variety of different organisms)
• 17,000 predicted (GenScan, GeneFinder, GRAIL)
• Based on and limited to previous knowledge

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Sequences complete for
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Sources of Complexity

• Gene number (2-3 fold over worm and fly)
• Alternative splicing (ca. 3 transcripts per gene
  vs. 1.3 for worm)
• Different organization (domains, subunits)
• New architecture (CNS, brain complexity)
• New abilities (Cognitive abilities)

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Challenge Opportunity

• To locate all of the genes in the human genome
  and describe their functions may take 15-20
  years!

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Whats the trouble?

• 1-3 coding sequences
• large number and long stretches of repetitions
• pseudogenes
• highly specific, rarely expressed genes
• paralogous genes
• regulatory regions
• short RNAs
• first and last exons
• splice variations

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Finding Genes Not Easy
in human genome

• Functional genes need to be detected in vast
  amount of non-coding human DNA.
• Repeats, pseudo-genes, and introns confound
  matters.

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What does it mean?

• 30,000 - 35,000 genes
• Average coding length 1.4 kb
• Average gene extent 30 kb
• Average gene density 11.5/1 Mb
• Y chromosome 6.4/1 Mb
• Chromosome 19 26.8/1 b

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Raw Genome Data
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Its all about patterns

• Promoters
• Open reading frames (ORF)
• Transcriptional and translational start and stop
  sites/codons
• Intron splice sites
• Enhancer signals
• Poly-A insertion sites

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