Toshio Morizane, MD

1
???????????????????

• ?????
• ????
• Toshio Morizane, MD

2
Science 2001?2?16???291?5507?1145-1434???

• Nature 2001?2?15???409?6822?813-941???

3
Annotation of The Celera Human Genome Assembly
4
?????????????????? 1998?????????

The C. elegans Sequencing Consortium Genome
Sequence of the Nematode C. elegans A Platform
for Investigating Biology. Science
19982822012-2018.
5
Human Genome Project???????

• ????National Institute of Health (NIH)?National
  Human Genome Research Institute
  (NHGRI)?????????NIH?Department of Energy
  (DOE)?2??????????
• ??Genome Center Institute of Medical Science,
  University of Tokyo

????????????????????!?????????????
6
???????

• ????????????????????????????????????????????????
  ??????????????????????????????????????????????????
  ??????????????????????????????????????????

7
1998-2003????

• 1-??DNA??
• 2-???????
• 3-???????????
• 4-?????????
• 5-??????
• 6-????????????
• 7-?????????????????
• 8-????

Science 1998 Oct 23 282 682-688.
8
1-??DNA??

• 2003???????????????????????
• 2001???????DNA???3??1???????
• 2001?????????????????????????90?????????????????
• ??????????????????????????

9
2-???????

• ???????????????????????????
• ???????????????????????????????
• ????????????????????????????????????

10
3-???????????

• SNPs????DNA??????????????????????????(SNP single
  nucleotide polymorphisms)
• ?????5????????????????????????????????
• ?????100,000?????SNP????????
• ??????????????????????
• DNA??????????????????

11
SNP single nucleotide polymorphisms STS
sequence-tagged sites

• SNP ?????????????(gt1)??????????
• STS DNA???????????????????PCR????????????????????
  ?? (24,568)

12
VDA variant detector array (DNA chips)
Wang DG, et al Large-Scale Identification,
Mapping, and Genotyping of Single-Nucleotide
Polymorphisms in the Human Genome. Science
19982801077-81.
13
4-?????????

• cDNA???????
• ???????????????????????????
• ?????????????????
• ?????????????????
• ??????????????

14
5-??????

• C. elegans???????1998???????
• Drosophilia??????2002????????
• ???????
• ???????????????
• cDNA??????????
• ?????????2005????????
• ???????????????????????????????????????

15
6.1-????????????

• ??DNA??????????????????????
• ?????????????????????????????????????
• ????????-??????????????????????????????

16
6.2-????????????

• ?????????????????????????????????????????
• ??????????????????????????????????????????????????
  ???????

17
7-???????????????

• ?????????????????
• ????????????????????????
• ?????????????????????????????
• ???????????????????????????????
• ???????????????????????????????????????????????

18
Bioinformatics?????

• Computational Biology?????????????????????????????
  ???2????3???(????)??????????????????????
• ???????????????????????????????????????
• ????????????????????????

19
8-????

• ????????????????????????
• ????????????????????????????
• ??????????????????????????????????????????

20
???????-1

• 1989?10?????????????????????????????????????????
  ???????????????????
• ?????????????????????????????????????5??(1991??19
  95?)??????????????????????????????????????????????
  ?????????????????????????????????????????
• ??????????????????????????????????????????????????
  ??????????????????????
• ??????????????????????????1994?6??????????????????
  ??????????????????????????????????????????????????
  ??????? ??II??????????????1995?4??????

21
???????-2

• ?????1996??2000???????????????????????????????????
  ?????????????????????????????????????????????
• ??????????????????????????????????????????????????
  
• ??????????????????????????????????????????????????
  ???????
• ??????????????????????????????????????????????????
  ??????????????????????????????????????????????????
  ??
• ???DNA??????????????????????????????

22
????

• ?????? HUGO (Human Genome Organization)
  ?1988?????????????????????????3??????????
• ??????????????????????????????????????????????????
  ?
• ??????????????????????????????????????21??????????
  ???????1??????????????????????????????????????????
  ??????????????????????????????????????????????????
  ?????? (???????????????????http//www.genome.ad.jp
  /Japanese/)

23
2001?1??????????

• Celera Genomics?
• Science???
• ?????????????????????????????????????????????????
  ????
• ??????????????
• Nature???
• ???????????????

24
?????????????

• ??3,000Mb 26,00038,000
• ????????180Mb 13,000
• ?? 97Mb 19,099
• ??????????????100,000???????????50????
• ???????????????????????

25
Homo Sapiens?????

• ???????????2,758???
• ?????2,031
• ??????????????1,523
• ?????????99???
• ??????????????????????

26
???????? Celera?

• 2.91 Gbp (?????)
• AT 54
• GC 38
• ??? 9
• ?????? 35
• ???(??) 26,383
• ???? 42
• ???(???) 39,114
• ???? 59

27
???????? Celera?

• ???????? 27Kbp
• ???????? 605Mbp
• ???????? 25.5-37.8
• ??????? 1.1-1.4
• ???????? 24.4-36.4
• ????DNA 74.5-63.6
• SNP?? 1/1,250 bp

28
????????? Celera?

• ?? 12,809?
• ?? 3,142
• ???????? 4,158
• ?????? 3,775
• ???? 577
• ???? 876
• ????????? 902
• ???????? 533

29
????????? Celera?

• ???????? 406
• ?????? 376
• ?? 296
• ??????????? 350
• ????????? 437
• ??/???? 203
• ????? 159
• ??????? 264
• Ca?????? 34
• ???????? 100

30
Paradigm Shifts in Biomedical Research

• Structural genomics ? Functional genomics
• Genomics ? Proteomics
• Map-based gene discovery ? Sequence-based gene
  discovery
• Monogenic disorders ? Multifactorial disorders

Peltonen L and McKusik VA Science 20012911224.
31
Paradigm Shifts in Biomedical Research

• Specific DNA diagnosis ? Monitoring of
  susceptibility
• Analysis of one gene ? Analysis of multiple genes
  in gene families, pathways, or systems
• Gene action ? Gene regulation
• Etiology (specific mutation) ? Pathogenesis
  (mechanism)
• One species ? Several species

32
Evans WE and Relling MV Pharmacogenomics
translating functional genomics into rational
therapeutics. Science 1999 286487-91. PMID
10521338