????????? ??? Human genome project and Computer science

1
????????? ??? Human genome project and Computer
science

• 2005-12-03 Biocom OB ???
• 93 ???
• http//biohackers.net/wiki/HgpAndComputer

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??

• ??? ?????
• Genome? ??
• ??????
• HGP ??? ????
• ?????? ??

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Genome

• ??? ???
• ???(gene), ???(genome)

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Great 3 books

• ?? ?? - ??

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Central Dogma of Molecular Biology
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Protein structure

• 20 Amino acids
• Sequence specifies conformation
• RNase

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Life

• DNAs common method of producing more DNA
• Review the life

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Evolution

• Self replicator

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Chromosome
1 cM 1 Mbps
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Gene structure
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Junk DNA

• ?? Genome? 5?? ???? ?? ??. ???? ?????
• Repetitive sequence
• LINE (gt300bps)
• SINE (300bps), Alu (3000050000?)
• Microsatelite

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Human genome

• 34x1014 cells (245)
• gt 200 cell type
• 3x109 bps (3Gbps 3Gbyte)
• 2000025000 Genes
• 98 unknown functional DNA
• 0.1 difference with you
• Information theory 30Mbyte

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Human genome project

• DOE, NHGRI ?? ??. 2003? ?? ??. 13?. 7?? ??
• 95? ?? Junk DNA ? ? ? ?? ?? ??? ??? ????
• ??
• Human DNA ?? ?? Gene? ??
• 30? ????? ??
• Database? ??? ??
• ?? ??? ? ?? ??? ??
• ?? ??? ??? ??

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History

• PCR
• RFLP
• Genetic marker
• BAC
• Shotgun sequencing
• Whole genome shotgun

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Gel Electrophoresis

• ?(???)? ??? ? ??? ??????, ???? ??. ???? ??
• DNA, Protein

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PCR

• Polymerase Chain Reaction

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Genetic marker

• Polymorphic allele locus

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Genetic map
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Cloning

• ?? ?? ? ??? ??? ?? ?? ? ??.
• ???, ?? ? ?? ?? ?? ?? ??

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Gene cloning

• Gene cloning ??
• Genome??? ??? ??? ???.
• ??? ??? ??? ? ?? PrimerDesign? ??.
• PCR? ????? major band? ????, ????.
• CloningVector? ????.
• Selection? ??? ??, ?? ???? ??? ??? ???? ??? ????.
  
• Cloning vector
• Plasmid
• Cosmid 30 kb
• BAC 350 kb
• YAC 2 Mb ??
• PAC 300 kb

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DNA sequencing
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DNA sequencing
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DNA sequencing

• Frederic Sanger
• DNA, Protein
• ????
• 700-800bp

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Shotgun sequencing
??? ?? ?? ?????? ?? ??? ?????? ?? ?, ????? ???? ?
???? ??? ??? ? ?? ??. ????? ?? ???? ?, ???
???????? ???? ???? ??? ??????. -- ?????, ?????
???
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Genome sequencing

• Clone by clone method
• Genetic marker? ?? BAC ?? ? shotgun
• Whole genome shotgun
• ??? shotgun
• Repeat ? ?? ???? ???.
• ???? ???.

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Current status (since 2003)

• Human Chromosome 4 Completed, April 2005.
• Human Chromosome 2 Completed, April 2005.
• Human Chromosome X Completed, March 2005.
• Human Chromosome 16 Completed, December 2004.
• Human Gene Count Estimates Changed to 20,000 to
  25,000, October 2004.
• Human Chromosome 5 Completed, September 2004.
• Human Chromosome 9 Completed, May 2004.
• Human Chromosome 10 Completed, May 2004.
• Human Chromosome 19 Completed, March 2004.
• Human Chromosome 13 Completed, March 2004.
• Human Chromosome 6 Completed, October 2003.
• Human Chromosome 7 Completed, July 2003.
• Human Chromosome Y Completed, June 2003.
• Human Genome Project Completion 1990-2003 (April
  2003)

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Genome browser

• UCSC Genome browser
• NCBI Genome browser
• Ensembl
• VistaBrowser

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Genetic disease before HGP
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Genetic disease after HGP
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Comparative genomics

• Synteny (Gene order), Gene duplication, Gene
  fusion

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Comparative genomics
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SNP

• Single Nucleotide Polymorphism
• ?? ??? ? ?? ???
• ???? ? ???? ? ?????? ? ????

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Haplotype
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(No Transcript)
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HapMap

• ??, ??, ??, ???, ??, ?????
• Project? ??? MinorAllele? ??? ?? 5 ???? ?? ??? 5
  kilobase ? 60?? SNPs? genotype ?? ?

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Transcriptome, Proteome

• EST
• DNA chip
• Proteomics

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EST

• Expression Sequence Tag

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(No Transcript)
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(No Transcript)
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(No Transcript)
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Transformational grammar

• Regular grammar computer program
• Context free grammar DNA
• Palindrome, ?? ?????
• Context sensitive grammar
• Unrestricted Grammar ???

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Sequence alignment
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Smith-Waterman algorithm
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BLAST

• Unknown sequence

Known sequence Database
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Object oriented programming

• Computer programming paradigm
• ????? ???

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???

• Rosetta stone
• Programming