Tools for understanding the sequence, evolution, and function of the human genome.
description
Transcript of Tools for understanding the sequence, evolution, and function of the human genome.
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Tools for understanding the sequence, evolution, and function of the human genome.Jim Kent and the Genome Bioinformatics GroupUniversity of California Santa Cruz
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The GoalMake the human genome understandable by humans.
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Step 1 Sequence the human genome
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Idealized Hierarchical Shotgun Sequencing
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Mapping300,000 BAC Clones Were Digested and Run on Agarose Gels Cari Soderlunds FPC and Wash U Pathfinders Made Fingerprint Map ContigsGenetic and radiation hybrid maps placed contigs on chromsomesBob Waterston escaping management
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Sequence and AssemblyBAC Clones shotgun sequenced at high throughput to 4x draft.Assembled with Phil Greens Phrap
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GigAssemblerJim KentDavid Haussler(meanwhile Celera working on whole genome shotgun version)
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The Truth+-?++?+-?--?+-?Keeping strands straight is the hard part+ light- darkness
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Finishing SequenceUsing primers to end of contigs close gaps.Checking automatic assembly especially near tandem repeats.Checking in-silico restriction digest of BAC matches actual digest.Time consuming - 1 year to draft genome, 2 years to finish.Human finished. Mouse will be finished (currently half finished). Other genomes may stay at draft stage, though draft stage can be very good these days.
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Now What?TGGCTTTTGAAGGGAGTTCTGTTTATATATACGTCAACATCCAGTTGGAGGTGAAAAGGTTAGCACTTGACCCAGGAAGTATCCATGTTTGTTTCAAAAA TAAATCTGCTTCATAAATTTCTTCATCAGTCTTTTTTTCCATTATGAGCTTTGATTATAATAAAGGAGCTGTTATTAACTTTTATTCAAGAAAAGGCCCA TCTCTTTGAAAATATTTACCACCCTTCTCCCTTTCCCCTCATGAAATGTGCCAACTTCATAGGAATTAACAAATTGTAGCCCAGCCAAATACACGGATGC TTAAGCATACCTGAAACTTGAGTATATTTATTTATTACAGACATCCTAAGACCCGTAAACTCTGCTCTGGATCATATCACTCCAGGATCTCAGAGCTGTT CATGATTGTACAGGAAATGGGGAATATCATAGGCTCACAAAGGATAACTGATAGAACTCAGTGTGGTACTTTGGGGACATCAAACATTGTGCGACATGCA AAAGACTATTCACGAATAACACAAAATATACATTCATTGTGCCATCCATCACATTAACAATTGAGCTGAAAATACATTATATCCAGCTAAGATAACTGTG GAAGGAAGAAATTGGTTTGAATAATACTTTTAGGTTCTGAATAACCCAGCACAAATTTTAAACAGAGGGTGGCCCGAGAAGAAAGGGGTAGAGATTGGGA AAGACTTAGCACAGGAAGCCGGGTTTCTGAAGTTTGTGCTCTGCAGGGCTTCTTAACTGTAAGAACAAATCAAGGCTACCCTCTGAGGCATCTGATTGGG TTTAAATGAGGGAATTTTTTCTTTCACCTATAAAATTGTACCAGTTTAGAGAGTTTGCCCACCCTGTTTTAGTAACCTAAACATTTCTAGAAAATCTGTA TAAAGATAAATCTCTTAGGACAAAGTATTTACAACCAGCAAACTCACACACATGAAAATGACTTAAATTAAGGGATGAATTAATTGTGTAAACATATAGT GCATCTCTTCTTCCTGAGCTCCTGGACTCGCCTTTCGCTATATCCTACTTTCAAGGACAAGGGAGGGGAGAGCTGTACATATAGTTAGATAAAAGATGAG AAGATTCCTTCTGGCATGTTTCTGTTGGCAAAGGGAACTATTTTCCAAAAGGTCATCTGAAAGGAACAGTAGGTTCTGTGAATTCTCCTAAAAGCAGGAG GGATGTTAAGGCCCACCAGAAAATGTATGCTGGCACCCAATCTGGATGAAGGTGTTAACCCCGCACCAAGTCTCTGGTCCAGAATTATCTGCAAATATAT TATCCTGGCCAGGAGCTCCCCAGATAGGATTAGAAAGGAAGAAAGAGACTGTAAATGGAAAGAAAGATAAGCTAAGCATGTGCTTTGGGTAAGAAGTCCC AGCCCAAGGAGATGCCTGGGCTGTTGTCTGGGGCTGGAGCCGCCTCAGTGGGAGGTAGTCAGAGTGTCTGAGGTAGAAGACCCCGGGGAAGGAACGCAGG GCGAAGAGCTGGACTTCTCTGAGGATTCCTCGGCCTTCTCGTCGTTTCCTGGCGGGGTGGCCGGAGAGATGGGCAAGAGACCCTCCTTCTCACGTTTCTT TTGCTTCATTCGGCGGTTCTGGAACCAGATCTTCACTTGGGTCTCGTTGAGCTGCAGGGATGCAGCGATCTCCACCCTGCGGGCGCGCGTCAGGTACTTG TTGAAGTGGAACTCCTTCTCCAGTTCCGTGAGCTGCTTGGTAGTGAAGTTGGTGCGCACCGCGTTGGGTTGACCCAGGTAGCCGTACTCTCCAACTTTCC CTGGGGCAAAGTGGGAAGCCATGAGACGGAAATGTAAAAATTTTTAAATCGACTTGAGATTCCCCACACGCTTCATGGCAACACTCAGGTAAAGAAAAGA TCAAGAACTCAGCACAAATCGGGCTGTGGAGGGTGAGTGATGAGGTGTAAAGTGTTAACCTGATGTAAACCATTAGCATGGTCAGACCGGTGATTAATGG AGCCTCAAGATATTAACAGAACACTACCGTCACAATAACCACCCCCACATACTTCCTATTTCCCAAATGTATAAAATCCTTGAAAACACACCAATCCCTG AGACTTCTTTGCCCCAACACCTCTGGGCACCCTCTCCATGCACTACAACACTAGTCTGATACAAAAGCCTTTTAAAAAAAAGATCATTATTAATTTCCTT GGAAATTAAGCATACCAGCTCCTTCCAGAATAATCAAGGAGCATCCACCAACCAGCAGGACTGACCTGTTTTGGGAGGGTTTCTTTTGACTTTCATCCAG TCAAAAGTCTGCGCTGGAGAAGATGTCTCCGATGCGGGGGAGCGACAGGCTTCTTGGTGGCTGGCGTGGAGAGGGGACAAGGAGTTATTATACGTAGCCA GGGCCAGGCTCTGGTGCTCCTGTCCATATGAGTGGTGAATGTATTGAGGCGAGCCCACCGCGCCCCCAGCATAACCCTGGTGGTGGTGGTGATGCTGGAC CATGGGAGATGAGAGATTTCCAGAGTAAACAGCGGGAGCGCACTGGGGGTACCCACCACTTACGTCTGCTTCCTGATTTAACGCGTAGGGGCTGTAAGGC GCACTGAAGTTCTGTGAGCCATAGCTTGGACCACAACTTGAGTGGGAGTAGGACACCCCCAGGTTCCCGGAAGTCTGGTAGGTAGCCGGCTGGGGGTGGC GATGGTGGTGGTGGTGGTGGTGGTGGGGCGAACCGATCTGCACCCCCCTGCCCACTAGGAAGCGGTCGTCGCCGCCGCAACTGTTGGCGCTGACCGCGCA CGACTGGAAAGTTGTAATCCTATGGTCCGAGGGGTAGGCTCGGGCTGAGCAGGTCCCCGAGTCGCCACTGCTAAGTATGGGGTATTCCAGGAAGGAGTTC ATTCTTGCATTGTCCATCTGTCACTGAGTGACCTGGTCCTGCGAAGCCCGGCGTGACTGTGCCAACTTTCTCACTTCCTC
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Finding the GenesDr. Blat helping a gene find itself.
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SIGLEC7 - a gene with some transcriptional complexity.Sialic Acid Binding/Ig-like Lectin 7displayed in UCSC Genome Browser
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Genes: Lines of EvidenceFull length human mRNA (the best!)Protein homology with other species.EST evidence - 1st step for much mRNA.Evidence from genome/genome alignmentsHMM based gene finders
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Transferrin Receptor in UCSC Genome Browser
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Clicking on a known gene brings up a large page of information on the gene.Transferrin
- Current state of human genome~99% of human genome sequenced. Last 1% will still be a challenge.~85% of human genes located. Substantial resources are being devoted to last 15%.~20% of human genes with any depth of functional annotation. Curation and integrated database are key to progress.
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Transferrin ReceptorNote peaks of conservation in 3 UTR. These include iron response elements which regulate translation of this gene.
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Comparative GenomicsWebb Miller
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Comparative Genomics at BMP10
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Conservation of Gene Features Conservation pattern across 3165 mappings of human RefSeq mRNAs to the genome. A program sampled 200 evenly spaced bases across 500 bases upstream of transcription, the 5 UTR, the first coding exon, introns, middle coding exons, introns, the 3 UTR and 500 bases after polyadenylatoin. There are peaks of conservation at the transition from one region to another.
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