M. Seri marco.seri@unibo.it Bologna 24 Gennaio 2009 Definitions - - PowerPoint PPT Presentation

• M. Seri

marco.seri@unibo.it Bologna 24 Gennaio 2009

Definitions Definitions

 Gene

Gene: Introduced by Johansson in : Introduced by Johansson in Copenhagen for Mendel’s unit of inheritance Copenhagen for Mendel’s unit of inheritance (1909). (1909).

 Genetics

Genetics: Introduced by Bateson in England : Introduced by Bateson in England for the science of inheritance (1905). for the science of inheritance (1905).

 Genome

Genome: First used by Winkler in Germany : First used by Winkler in Germany (1920) for GENes and chromosOMEs, i.e. the (1920) for GENes and chromosOMEs, i.e. the complete set of chromosomes and the genes complete set of chromosomes and the genes they contain. they contain.

 Genomics

Genomics: Structural and functional study of : Structural and functional study of genomes (Roderick, Bar Harbor, Me. 1986). genomes (Roderick, Bar Harbor, Me. 1986).

La Genetica Medica è basata sullo studio di malattie genetiche rare, ereditate in modo “mendeliano” La Medicina Genetica implica il fatto che la genetica pervade tutta la medicina, incluse le malattie comuni come l’ipertensione, il cancro, le malattie cardiovascolari, etc. (= malattie genetiche complesse)

Medicina Genetica versus Genetica Medica

 1985 - Proposed

1985 - Proposed

 1986 - 89 - Discussed,

1986 - 89 - Discussed, debated, and planned debated, and planned

 Oct. 1, 1990 - Official start

• Oct. 1, 1990 - Official start

date date

 Sept. 30, 2005 - Projected

• Sept. 30, 2005 - Projected

completion date completion date

The Human Genome Project The Human Genome Project

Progetto Genoma Umano Progetto Genoma Umano

tataactca tccatttact cagaactcac cattgccgcc atgttcccct aacttcatga ctgcaaagg ggtagttgtt ctccatggga ccacccgccc ccaccccccc caccgccccc acccggcaa cacgaaagca aaccaggtgc gcggaagcta gggaaagctg ttcaaagcca gaaagtgag actgtcactc gtgagctttc tcgccaggca gcatatcctt ctgtctcagc tggttccct gcctccgtga ctgatttcct gcaggatggc attcagatct tttgaagcgt cacatcctg cccagacaca caccctgaat gtcaacctgt aatcctaact gtgacaattt tagagttgg ataagtcaga tgctctccaa ggctgatgct tgccctgaca cattgtgcgt tcgtgcatt gcgttcaata caagaggtgc tgacgaggca ggtccattct cttgtctaac ctaatgatc attctccctg agttgttggc agggggctgc tggcgtggaa ggaaaggaaa aagaggctt tgcttctctc tgccctcgga ggggaatggg gatgagctgg atgtttgaac aggtcaggg atctaggctg tgagcaattt gaaaacaaaa caaaactgtg gcgttctgca agctcagct gcacataaag aaacactctg cgtgtgcctc ccagaactgt gtggtctgcc ttttgaaat ctttctcaag gaaactctaa aagttgacct gggtctgtta ttaggcccta tgaaactgt aggagacgcc aggaccctgt gaagacagct gaggctcggt ggacactgct attgaagga tttagccttc tgagtcgttt ttgttgctgt gagttttctt tgttatgttt ttttgggag tcttgacttg ctgatccaag gagatttgct tttccttttc ccactggaaa cttccgtag ttgccagcct ggtcttcaat gagaagtatg gtctggaagc ttgaaacatc ttcataaac tctttcttga actgtgcctt actaactggt cagaagtctg ctcatcaacc aaacttcat ttaataaaag gaataaacct gctttcattt tgaaatgttt tcagctgata gcacagtaa acctctgaaa acttgcccct ctccaccacc cacagattaa tttcattgac acaggtgtt caaagacttc gcatggctgt aaccaggttc atctcattcc ccggctgtaa aatttgcta accaactgtc ctttaatcct tcaggagtct tggattcagt cttcaatttt gaccttttc ttttcagaca tggatcttac aaaaatctgc actgggaagg gagcggtgac ctccgggcc tcgtcttcct acagggaaac cccaagcagt agccctgcga gccctcagga gtgggaagg gcgggaggag gctctggtgt ttttgctcag gagggtgtga gttcatcaga acctcttgg gggggggggg tgtgtgtgtg tgtgtgtgtg tctcttacgg tcccctggga agtcaaatc atttggatgg gtagtggtca aagcctcaaa ctgacagtca catgctgcag tgaaggcac agcaataacc acactttatg ttagctttga ctgagcaggt catcctgtga

Methods in Human Genetics

1960 1970 1980 1990 2000

‘Chromosomology’

1956

Somatic Cell Genetics

• Gene mapping
• Inborn errors of metabolism
• Somatic mutations in cancer

Molecular Genetics

Transgenic, KO, etc, mice

Database searching

‘In silico cloning’ “ DNA chips ”

Microarray technology

2010

MENDELIAN INHERITANCE IN MAN MENDELIAN INHERITANCE IN MAN ( MIM ) ( MIM )

 CATALOG OF AUTOSOMAL DOMINANT,

CATALOG OF AUTOSOMAL DOMINANT,

 AUTOSOMAL RECESSIVE, AND

AUTOSOMAL RECESSIVE, AND

 X-LINKED PHENOTYPES

X-LINKED PHENOTYPES

 1^ edizione 1966: 1500 voci – oggi: >14000

1^ edizione 1966: 1500 voci – oggi: >14000

 Dal 1998: solo in forma elettronica:On-lineMIM

Dal 1998: solo in forma elettronica:On-lineMIM

 http://

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

Comparative Genomics

disease models

biochemistry crop yield behavior development

medicine

infectious disease genetics

microbes Arabidopsis

• C. elegans

Drosophila human mouse yeast

physiology

rat

Power of Comparative Genomics Power of Comparative Genomics

• Understanding the

Understanding the human genome human genome through comparative through comparative genomics genomics

• Evolution preserves

Evolution preserves function between function between species species

• Genome comparisons

Genome comparisons increase the increase the interpretative interpretative capability capability

Mutations in the Pax-6 gene of Drosophila cause an eyeless phenotype Mutations in the Pax-6 gene of humans causes Aniridia “no iris” phenotype

The The child is child is blind blind The fly is blind The fly is blind

Genetic Medicine Paradigm Genetic Medicine Paradigm

Information: Critical to Understanding Disease Mechanisms

Y Y

RNA Proteins Modified Proteins DNA Biological Function Transcription Translation Post-Translation Modification 30,000 Genes > 1,000,000 Proteins

Cloned human genes Genes with mutations causing human disorders

Total ~ 30,000 genes

SEA 3017

About 4000