Antonio Amoroso

Universit degli Studi di Torino Dipartimento di Genetica Biologia e Biochimica Facolt di Medicina e Chirurgia

Azienda Ospedaliera S. Giovanni Battista di Torino S.C. Immunologia dei Trapianti

DNA ieri, oggi, domani

Ieri: la scoperta della struttura del DNA e della sua funzione Oggi: le conoscenze del genoma umano Domani: le ricadute in medicina e le possibili applicazioni cliniche

DNA ieri, oggi, domani

Ieri: la scoperta della struttura del DNA e della sua funzione Oggi: le conoscenze del genoma umano Domani: le ricadute in medicina e le possibili applicazioni cliniche

1953

Rosalin Franklin

1955

1957 la nuova 500 1959 la 1800

1961

1964 - 1966

1971

1974 1975

1978 - 1980

Nel 1980, iniettata la prima insulina biosintetica (DNA ricombinante) di formula umana (Eli Lilly: ingegneria genetica sulla cellula del batterio Escherichia coli) a Sandy Atherton, 37 anni, di Wichita, Kansas.

1988

1990: Michael Blaese negli Stati Uniti effettua la prima procedura di terapia genica su una bambina affetta da SCID, una grave immunodeficienza ereditaria

1992

1993

1996

How many genes?

300.000 30.000

about 500 1.000-page phone books

2003
1953

DNA ieri, oggi, domani

Ieri: la scoperta della struttura del DNA e della sua funzione Oggi: le conoscenze del genoma umano Domani: le ricadute in medicina e le possibili applicazioni cliniche

DNA ieri, oggi, domani

Ieri: la scoperta della struttura del DNA e della sua funzione Oggi: le conoscenze del genoma umano Domani: le ricadute in medicina e le possibili applicazioni cliniche

The exons represent only about 1.5% of the entire genome

Gene A

Gene B

1.5%
Coding Sequences

98.5%
Junk DNA

Non Coding DNA

Marzo 2010
PANTHER Pie Chart

25.431 reviewed genes

10934 genes as "molecular function unknown

http://www.pantherdb.org

http://www.ncbi.nlm.nih.gov/Omim/

Quasi 6000 Malattie ereditarie o monogeniche

wildtype allele

mutant allele

wildtype phenotype

mutant phenotype

Cystic Fibrosis

2008

Genome Projects on other organisms

Organism complexity and gene number

Escherichia coli Saccharomyces cerevisiae Caenorhabditis elegans Drosophila melanogaster Danio rerio Mus musculus Homo sapiens 3,200 6,300 19,100 13,600
21,322

Genome size

22,000 22,000

Fugu rubripes 26,700 Arabidopsis thaliana 25,000 Tetrahymena thermophila 27,000

Number of genes

Gene number does not always correlate with evolutionary status

Houston, TX - 31 May 2007, Richard Gibbs and Jim Watson

James Watson

Genomics goes personal

- The first human genome decoding, completed by the public consortium in 2003, cost more than $ 1 billion

454 Genome Sequencers $ 2 million

Applied Biosystems Sequencers $ 10 million

Craig Venter

Personal Genomics
- Many scientists are competing in a challenge issued by the NIH to produce a sequencing method that costs: $100,000 less than per genome by 2009 $1,000 or less by 2014

- X-Prize Foundation is offering $10 million - the largest medical prize in history - for the first private team that can decode 100 human genomes in 10 days

How to build a Homo sapiens

How to build a Homo sapiens

How to build a Homo sapiens

Identical twins

How to build a Homo sapiens

How to build a Homo sapiens

2007

DNA ieri, oggi, domani

Ieri: la scoperta della struttura del DNA e della sua funzione Oggi: le conoscenze del genoma umano Domani: le ricadute in medicina e le possibili applicazioni cliniche

Discovery of the RNA continent

DNA
Non-coding RNA 23,218 (53%) Protein coding RNA 20,929 (47%)

Transcription
20,929

Transcription

23,218

Protein coding RNA

Until FANTOM2 in 2002, only ~ 100 ncRNAs genes were reported except tRNAs and rRNAs. More than half of the genes have been missing from the gene maps till that time. Translation

Non-coding RNA

No translation!

Protein Nature, volume 420, (December 5, 2002)

Conserved Non-Coding Sequences

About 5% of small segments in the human genome are under evolutionary selection for biological functions common to human and mouse
CNS (3.5%) Exons (1.5%)

Human genome
CNS Exon CNS Exon

Mouse genome

Correlating biological variation and variation in DNA sequence

aattggaagc gagtagtagg gcccgagaga ttcagctgga atataccaaa tgggatagag tttttctgga gtacagcctc cgctctatcg ctcctacacc tttagtttga attggacaac ttggcacatt gagttgttac caggctgggc gaaagacttg tgggaagaag cggaaggcag gtggtgtttt ttcaccacca gctgtacaaa aagcaagaat gtaacagcct aacaatagaa ggtactcctg gctggatcca ccttcagagg attatgcctg tacagaagcg gacaatatag aaatgacatc tctttggcat ccatgcagag ccagaccaat tcccttctgt agctggcttc gatttatgtt tcttactggg cgatttatct cagccatttt tttataagaa ttgttagtct tcgtgtggat aggcgtctgc tagggagaat tgattacctc caatggaaaa cctatgtgag tatctgtgct tctcattctg catggtatga ataagacatt tctgggagga aaacttctaa tcctgaaaga ctggagcagg gtaaaattaa gcaccattaa tcatcaaagc ttcttggaga acagcaggtc taggagcttg gtcgcctctg tttgaggaaa tgattctgct aaagaaaaat ctatggaatc aagaatcata aggcataggc tggccttcat gactttaaag cctttccaac cgctcctttg cttctgtgga gatgatgaag agaaatgatt aatgattgaa atacttcaat tccctatgca cattgttctg ctctcttgga ggaatataac gggatttggg tggtgatgac tattaatttc caagacttca gcacagtgga agaaaatatc atgccaacta aggtggaatc agagaaaaag agcccagacg gaaaaggcca ggatacagac gacaatctat cctaaactca tttttatatt gcttcctatg ttatgccttc cacattggaa ctgtcaagcc aacctgaaca caagtggcac cttggtttcc tacagagatc gaaaatatcc aacttaagac agctcagcct ctaatcaaag cgcatggcgg gcaataaaca ttaacgacta gaattatttg agcctcttct aagatagaaa cttctaatga agaatttcat atCTTtggtg gaagaggaca acactgagtg ggttgagcgg gccctagcag gcgttgtctc agcgcctgga ctgaaaaatt ttaatgccct taggggaagt acccggataa tctttattgt tgcagatgag gtgttctaga aatttgatga tcctcatggg tgatagtcct agagagctgg aatctgttaa aaacagaact tcttcttctc gaatcatcct tcactcggca aaatacagga cagaagtagt agaaagcaaa tcagtaattt gaggacagtt tgattatggg tctgttctca tttcctatga tctccaagtt gaggtcaacg

agaatttca at[T/C]gt aagaggaca

caggcaccca ggaccccagc caaacttttt attgtcagac ggaaagagaa tcggcgatgt caccaaagca caaggaggaa gaggacactg aatagctatg taaaataagt aggacttgca gctaatctgg tgcccttttt gaagatcagt ggcatactgc gaaactgact agggttcttt ccggaaaata atttccctgg tttcttacaa gatggagaat acaaaacaat ctcacttctt gttggcggtt agaactggag gttttcctgg tgaatatag tgcagagaaa agcaagaatt

Health card

Today

Tomorrow

Do we really want to know the sequence of our genome.?

Personal Genome

Non ho ricevuto alcun finanziamento dalla FIAT

Thanks
The Sequence: Inside the Race for the Human Genome by Kevin Davies

antonio.amoroso@unito.it