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Genes & Medicine: How DNA is Improving Your Health U3A Mountford, June 2004. Dr Martin Kennedy Department of Pathology Christchurch School of Medicine & Health Sciences University of Otago. What this talk is not about.

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genes medicine how dna is improving your health u3a mountford june 2004
Genes & Medicine:How DNA is Improving Your HealthU3A Mountford, June 2004
  • Dr Martin Kennedy
  • Department of Pathology
  • Christchurch School of Medicine &
  • Health Sciences
  • University of Otago
what this talk is not about
What this talk is not about

No, I’m not the waiter. I’m the genetic engineer. How would you like your lamb?

what this talk is about
What this talk is about:
  • Why is genetics important?
  • Disease genes
    • inherited disease
    • complex diseases
  • The human genome project
  • Genetically modified animals
  • Treating disease
    • finding new drugs
    • tailored drug treatment
    • gene therapy
conquering disease
Conquering disease
  • Recognition and naming
  • Observation and measurement
  • Understanding of aetiology/pathology
  • Understanding of molecular mechanisms

Development of treatments

& preventative strategies

why try to understand genes
Why try to understand genes?
  • To provide a window on the disease process
  • Diagnostic or prognostic markers
  • Drug targets
  • Prediction/prevention

The vast majority of our knowledge about human genes comes via genetic modification techniques

genetics contributes to most disease

Environment

Genetics

Genetics

Genetics

Environment

Environment

cystic

fibrosis

adult onset

diabetes

AIDS

Genetics contributes to most disease
genetics contributes to most disease1

Environment

Genetics

Genetics

Genetics

Environment

Environment

cystic

fibrosis

depression

AIDS

Genetics contributes to most disease
genetics contributes to most disease2

Environment

Genetics

Genetics

Genetics

Environment

Environment

cystic

fibrosis

coronary artery disease

AIDS

Genetics contributes to most disease
slide15

Genetic disease

  • Mendelian disease
    • one gene
    • genes are causative
    • genetic mutations
    • environmental influences
  • eg CF, PKU, haemochromatosis
slide16

Genetic disease

  • Complex disease
    • polygenic
    • genes confer susceptibility or risk
    • genetic variants (polymorphisms)
    • environmental influences
  • eg Diabetes, IBD, CAD, autism, anorexia, coeliac disease, Alzheimer’s, asthma, bipolar disorder
slide17

Genetic disease

  • Congenital disorders
    • loss or gain of genes
    • usually sporadic
  • eg Down’s, Williams, PWS
slide18

Cancer

  • All cancer is caused by damage to genes
  • Damage to several or many genes is required to initiate and progress cancer
  • Some cancers display an inherited susceptibility
the human genome

The Human Genome

“This scaffold has been handed down to us from our ancestors, and through it we are connected to all other life on earth.”

Svante Pääbo, 2001

understanding major disease
Understanding major disease

Alzheimer’s Disease Third leading cause of death

Asthma Affects 150 million people worldwide

Breast cancer Accounts for 20% of female deaths

Heart disease The world’s biggest killer

Migraine 1.4 billion attacks worldwide each year

Depression Ranked 4th in W.H.O. global burden of

disease analysis

slide27

Isolation of “susceptibility genes”

Korstanje & Paigen 2002, Nature genetics 31, 236-7

major outcomes of hgp
Major outcomes of HGP
  • Discovery of:
    • causative genes in Mendelian disorders
    • susceptibility genes in complex disease
  • Improved:
    • drug design
    • drug treatment
    • disease management
  • Understanding of human history
completed microbial genomes
Completed microbial genomes
  • 165 Bacteria including:
    • Yersinia pestis
    • Helicobacter pylori
    • Haemophilus influenzae
  • 1790 Viruses including:
    • SARS
    • HIV
    • Several herpes viruses
    • Several papilloma viruses
    • Several influenza viruses
    • Polio
transgenic organism
Transgenic organism

A plant, animal or microbe that has incorporated, in its own genome, genetic material from another organism.

transgenic mice
Transgenic mice
  • Adding genes

“Conventional” transgenics (developed early 1980s)

  • Subtracting genes

“Knockouts” (developed late 1980’s)

why transgenic animals
Why? Transgenic animals
  • Understanding gene function
  • Modelling diseases
  • “Bioreactors” for vaccines, drugs, etc
nature genetics 2000
Nature Genetics, 2000
  • Approximately 280 research papers. Of these, 80 (28%) directly focused on GM mice:
  • Cancer: 11
  • Cardiovascular disease: 7
  • Development: 15
  • Neurological or behavioural: 11
  • Reproduction: 7
  • Obesity and diabetes: 7
  • Vision or hearing: 7
  • Technology development: 9
    • (including two large scale international programs that generated and screened 40,000 mice, producing 747 new mutants)
  • Others: 6
ge and drug development
GE and drug development
  • Identification of new drug targets
  • Production of drugs
  • Structure aided drug design
  • Pharmacogenetics
pharmacogenetics
Pharmacogenetics
  • The study of genetic variation underlying differential responses to drugs
why pharmacogenetics
Why pharmacogenetics?
  • Prediction of adverse drug reactions
    • 100,000 deaths annually and 2 million hospitalizations (USA alone)
  • More appropriate prescribing
  • Medicines targeted for specific genotypes
  • Rescue “failed” drugs
  • Making better use of existing drugs
where is gm in medicine taking us
Where is GM in medicine taking us?
  • Better understanding of mammalian biology
  • Better understanding of disease
  • Improved ability to predict disease
  • Improved ability to diagnose disease
  • Improved ability to control disease
    • safer, more specific drugs
    • gene guided management
    • gene therapy