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The Human Genome Project

The Human Genome Project. Public: International Human Genome Sequencing Consortium (aka HUGO) Private: Celera Genomics, Inc. (aka TIGR). The HGP. 1st proposed in 1986 In addition to humans, the effort included E. coli, yeast, C. elegans, Drosophila, and mouse. Funded in 1988

wayne-campbell
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The Human Genome Project

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  1. The Human Genome Project Public: International Human Genome Sequencing Consortium (aka HUGO) Private: Celera Genomics, Inc. (aka TIGR)

  2. The HGP 1st proposed in 1986 In addition to humans, the effort included E. coli, yeast, C. elegans, Drosophila, and mouse Funded in 1988 Estimated cost: $3 billion Final cost: $2.6 billion Got underway in 1990 1st genome sequenced in 1995 (TIGR) Yeast sequenced in 1996 E. coli sequenced in 1997 C. elegans sequenced in 1998 Drosophila sequenced in 2000 (Celera)

  3. The Human Sequence Human draft sequence released in Jan. 2001 (HUGO & Celera) The genome was sequenced about 4 times over Contained errors and gaps Gaps can exist: 1) within unfinished sequence clones 2) between sequenced BACs 3) between mapped BACs The finished sequence, released in April of 2003, was sequenced 8 times over, had 1 error in 10,000 bases and did not contain significant gaps

  4. The “Typical” Human Gene

  5. The Number of Human Genes

  6. # of Genes in Other Organisms

  7. Orthologs of Human Proteins

  8. Where did the prokaryotic orthologs come from? • One possibility is horizontal transfer 41 genes may have been transferred in this way For example: MAOs, monoamine oxidases These enzymes deactivate neurotransmitters • Another possibility is the loss of these genes over time so that most eukaryotes lack them

  9. Functional Categories of Proteins

  10. Families of Transcription Factors

  11. Some surprises from the HGP • Not every gene encodes a protein • Not every gene has its own promoter • The number of genes in our genome Promoters: a number of adjacent genes are transcribed simultaneously. These genes were shown to share a promoter, much like prokaryotes control gene expression.

  12. Genes that do not encode proteins • tRNA • rRNA • snRNAs (small nuclear RNAs) • snoRNAs (small nucleolar RNAs) • ncRNAs (non-coding RNAs) These are untranslated genes such as the let-7 gene in C. elegans. It encodes a 21-base RNA that binds to another gene

  13. How Can We Have So Few Genes? We are not just 1.5 times as complex as flies, even though we have about 1.5 times the number of genes. If each gene has 2 states: on or off, then there are 213,600 different combinations in Drosophila but 221,000 different combinations in humans. • Combinatorial Control • Alternate Splicing • Epigenetic Control

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