1. Next Generation Sequencing and Human Genome Databases
Genomics, Bioinformatics & Medicine
I have been asked to speak to you about the impact that the human genome project will have on biomedical research and education.
It is clear that the new fields of genomics and bioinformatics will have the same revolutionary effects on medicine as they have had on molecular biology and biomedical research. I would like to present you with a vision of that revolution and some of its implications for medicine and medical education in particular.
I would first like to call your attention to some reference materials that can give you further background on these issues:
Scientifc American Introduction to Molecular Medicine, just enough, BMA.
Science Magazine features the Human Genome project, Lee Rowan (sequencing human genome), Phil Hieter on Understanding the Human genome, Joe Derisi, current graduate students (studying gene expression)
MIS Short Course on Medical Informatics
- you may see a videolectures here
Doug Brutlag
Professor Emeritus of Biochemistry & Medicine
Stanford University School of Medicine

2. The Human Genome How fast is the cost going down?
2006: $ 50 million
2008: $500,000
2009: $50,000
2010: $20,000
2011: $5,000
2012:??? $1,000
Thanks to Serafim Batzoglou

3. Components of a Typical Human Gene
Intron
Exon
Promoter
Terminator
TFBS

4. Active Genes are Transcribed into RNA
Primary
Transcript
Gene
Intron
Exon
Promoter
Terminator

5. Splicing Transcript Yields Mature mRNA
Gene
Intron
Exon
Promoter
Terminator 5’ 3’
Splicing

6. Mature mRNA contains Coding Region and 5’ and 3’ Untranslated Regions
Transcript
mRNA
Gene
Intron
Exon
Promoter
Terminator 5’ 3’
Splicing
Coding Region
5’UTR
3’UTR

7. Mature mRNA contains 7-Methyl-Guanosine 5’ Cap and 3’ Poly A Tail
Transcript
mRNA
Gene
Intron
Exon
Promoter
Terminator
Splicing
Coding Region
5’UTR
3’UTR
7-Me-G-Cap
3’ Poly A Tail

8. ESTs, Full Length cDNA UniGene & RefSeq Databases
Transcript
mRNA
Gene
Intron
Exon
Promoter
Terminator 5’ 3’
3’ ESTs
5’ ESTs
Full Length cDNA
Splicing
UniGene & RefSeq

9. ESTs, Full Length cDNA UniGene & RefSeq Databases
Transcript
mRNA
Gene
Intron
Exon
Promoter
Terminator 5’ 3’
3’ ESTs
5’ ESTs
Full Length cDNA
Splicing
Proteins
5’ UTR
3’ UTR
UniGene & RefSeq
5’ UTR
3’ UTR
Protein

10. GENSCAN Gene Model http://genes.mit.edu/GENSCAN.html
Hidden Markov models of gene structure

11. Genome Databases Genomic DNA A Mapping B Gene Prediction
Assembled contigs
A Mapping
uniSTS
dbSNP
GrailEXP
B Gene Prediction
GenScan
FGENESH
FGENESH+
GeneMark
Mouse
ESTs
Human
C Expression Data
Entrez Gene
RefSeq
UniGene
Ensembl
cDNA
nrPRO
D Protein Similarity
pFAM Motifs
Takes Hardware!
Everything in parallel
Genome Databases
Promoters
E Additional Data
F Summary
Entrez Gene
UCSC Browser
Ensembl

12. Entrez Gene Loci http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene
NR-Pro
Inclusive
Exon Prediction
UniGene
ESTs
Genscan
GrailEXP
FGENESH
Here it is—go through in order…
Left off FGENESH+ for the sake of a less cluttered slide.
NR-Pro
UniGene
ESTs
GrailEXP
FGENESH
Genscan
Entrez Gene
Entrez Gene

13. Alternative Splicing Generates Distinct Proteins in Different Tissues
Promoter
Exon
Intron
Exon
Intron
Exon
Terminator
Gene
Transcript
Splicing
mRNA-1 3’ 5’
Alternate Splicing
Transcript
mRNA-2 5’ 3’

14. NCBI Genomes http://www.ncbi.nlm.nih.gov/sites/entrez?db=genome

15. Eukaryote Genome Projects http://www.ncbi.nlm.nih.gov/genomes/leuks.cgi

16. NCBI Entrez Gene http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene

17. NCBI Entrez Gene: Human Opsin http://www. ncbi. nlm. nih. gov/gene

18. Entrez Gene: Human Opsin OPN1MW http://www.ncbi.nlm.nih.gov/gene/2652

19. Entrez Gene: Human Opsin OPN1MW http://www.ncbi.nlm.nih.gov/gene/2652

20. MapViewer: Human Opsin OPN1MW http://www.ncbi.nlm.nih.gov/gene/2652

21. Evidence Viewer for OPN1MW http://www. ncbi. nlm. nih. gov/sutils/evv

22. OMIM Home Page http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

23. Colorblindness in OMIM

24. Colorblindness in OMIM http://omim.org/entry/303800

25. Human Genome Resources http://www.ncbi.nlm.nih.gov/genome/guide/human/

26. RefSeq http://www.ncbi.nlm.nih.gov/RefSeq/

27. RefSeq Gene http://www.ncbi.nlm.nih.gov/refseq/rsg/

28. NCBI UniGene http://www.ncbi.nlm.nih.gov/sites/entrez?db=unigene

29. NCBI Homologene Database http://www.ncbi.nlm.nih.gov/homologene

30. Ensembl Home Page http://www.ensembl.org/

31. EBI Genomes Home Page http://www.ensembl.org/

32. Ensembl Human Genome http://www.ensembl.org/Homo_sapiens/

33. Ensembl Human Opsin Search http://uswest. ensembl

34. Ensembl Human Opsin Genes http://uswest. ensembl

35. Ensembl Human OPN1MW Gene http://uswest. ensembl

36. Ensembl Opsin OPN1MW Gene Location http://uswest. ensembl

37. Ensembl OPN1MW Transcripts http://uswest. ensembl

38. Ensembl OPN1MW Opsin Protein http://uswest. ensembl

39. Ensembl Tutorials http://uswest. ensembl

40. UCSC Genome Home Page http://genome.ucsc.edu/

41. UCSC Genome Browser http://genome.ucsc.edu/cgi-bin/hgGateway

42. UCSC Genome Browser http://genome.ucsc.edu/cgi-bin/hgGateway

43. UCSC Genome Browser http://genome. ucsc. edu/cgi-bin/hgTracks

44. UCSC Genome Browser http://genome. ucsc. edu/cgi-bin/hgTracks

45. UCSC Proteome Browser http://genome.ucsc.edu/cgi-bin/pbGateway

46. UCSC Proteome Browser http://genome.ucsc.edu/cgi-bin/pbGateway

47. UCSC Help File http://genome. ucsc. edu/goldenPath/help/hgTracksHelp