知っておきたい 遺伝子・ゲノム ... - tmd.ac.jp

1 Hayashi ShinFeb 22, 2013 5 1. 2. 3. 4. Today s menu .. 15 ( cause of a disorder 10% 25% 65% 1~3% 3% 2/3 1997 2005 HP [ ] So, what s a genome? ..DNA DNA [ ] DNA DNA DNA Chromosome and DNA 1842 ( , )1865 ( , )1869 DNA ( , )1902 ( , )1930 DNA 1953 DNA ( , )1959 ( , ) 1960 ( , ) Human Chromosome 46 22 2 2 46,XY, 46,XX DNA So, what s a chromosome?)

2 ( ) 38 ( ) 33 [ ]* * DNA So, what s a DNA?DNA ( ).. [ ] [ ] What s Central dogma ?DNA RNA ..A G C U G A C CU A G C G GA C A AC GCAlamRNA 3 mRNAG A ULeuAlaAspLeutRNA 20 DNA [ ]DNA DNA [ ] (Synthesis= )DNA (Mitotic= ) G2 (Gap= ) G1 (Gap= ) [ ] Division and differentiationiPS (= ) SNP >1%.

3 100 ..CAG CAG CAG CAG CAGCAG CAG CAG >1000bp 30% CNV CNV CNV CNV CNV CNV HIV [Perryet al. Nat Genet . 2007][Gonzalez et al. Science. 2005]CCL3L1 AMY1A CNV 100 300 BAC (WGA-15000), BAC (WGA-4500),SNP CNV MCG CNV HP ( ) ( ) ( ) [Nussbaumet al. Thompson&Thompson Genetics in Medicine, 7th Edition. Saunders,2007] What s a genetic disorder?

4 (Genetic Disorder) Human chromosomes 21 3 [ ] Chromosome for diagnosis[Hennekamet J Med Genet. 2011] Difficulty of diagnosis1,000,000,000= 1 Gbp100,000,000= 100 Mbp10,000,000= 10 Mbp1,000,000= 1 Mbp100,000= 100kbp10,000= 10kbp1,000= 1kbp100bp10bp1bp3,000,000,000= 3 Gbp(bp: ) Human genome and analyses 1950s~ 1bp 1970s~ 2000s~ 1bp Later 2000s~ 1~3% 3% [Hunter, 2000]10~15% 5~20% 5 CGH DNA ( ) ( )MCG, MRI, TMDU Method of a microarray (copy number variants.)

5 CNV) MCG, MRI, 1kb ( ) DNA ( ) ( ) 1, 9 ..Chromosome was analyzed 9 1919 Microarray discovered! 1 9 1919 (MR/MICPCH) CASK[Hayashi et al., Am J Med Genet A. 2008][Najm et al.,Nat Genet. 2008]del(X)( ) mutationNonsense mutationFrameshiftmutationFrameshiftmuta tiondeletionIntragenic duplicationMICPCH CASK MR/MICPCH 10 ~ SD 2005 20011000 1 GA (illumina/Solexa)454 (Roche)SOLid (ABI) ABI / HITACHI 3730xlIon torrent PGM (Life technologies)PacBio RS (Pacific bioscience) 2010 20112012~600 Gbp / run70 / HiSeq2000 (illumina)2008 Watson (67 ) (ICGC) 20071000 2003 HapMap ENCODE 115 kbp /day1 Gbp = 10 3 GbpGAIIx (illumina)50 Gbp /run20041000 1991 (NIH)(15 30 )MCG, MRI, TMDU1000 /13 43.

6 Genome analysis acceleration[Mardis. Nature 2011]NIH [ ] Personal Genome Era is coming? 45 ..Thank you very much for your attention !MCG, MRI, TMDU**