GENOMICS AND HUMAN GENETICS IN MEDICINE - PowerPoint PPT Presentation

Loading...

PPT – GENOMICS AND HUMAN GENETICS IN MEDICINE PowerPoint presentation | free to view - id: bf1c-NWVhO



Loading


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation
Title:

GENOMICS AND HUMAN GENETICS IN MEDICINE

Description:

GENOMICS AND HUMAN GENETICS IN MEDICINE. Vivian G. Cheung, MD ... Sequences of 24 complete genomes and soon the human genome. GENETICS AND GENOMICS: ... – PowerPoint PPT presentation

Number of Views:300
Avg rating:3.0/5.0
Slides: 24
Provided by: vche
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: GENOMICS AND HUMAN GENETICS IN MEDICINE


1
GENOMICS AND HUMAN GENETICS IN MEDICINE
  • Vivian G. Cheung, MD
  • University of Pennsylvania
  • The Childrens Hospital of Philadelphia
  • Department of Pediatrics

2
MEDICINE IN THE 21st CENTURY
  • MARRIAGE OF GENETICS AND GENOMICS

3
GENETICS
  • The study of heredity (variation)
  • Progress
  • Mendels Law
  • Discovery of chromosome, DNA
  • Discovery of disease genes (CF,
    Huntington)

4
GENOMICS
  • The study of genomes - a global approach to
    cells, organs and organisms at the DNA, RNA and
    protein levels.
  • Progress
  • High-throughput technologies
  • Sequences of 24 complete genomes and soon
    the human genome

5
GENETICS AND GENOMICSTODAY
  • Genetic variants disease and drug metabolism
  • Human genome sequence gene content
  • Gene expression profiles catalogue of genes
    expressed in each tissue type and in different
    cellular functions.

6
GENETICS AND GENOMICSTOMORROW
  • Diagnosis
  • Treatment
  • Prevention

7
MODEL ATAXIA TELANGIECTASIA
  • Work in progress
  • Illustrates how combining genetics and genomics
    can improve diagnostic tools, therapies, and
    preventive measures.

8
ATAXIA TELANGIECTASIA
  • Autosomal recessive disorder mutations in ATM,
    chromosome 11q22-23.
  • Progressive neuromotor dysfunction, immune
    deficiency, telangiectasia, and predisposition to
    cancer.
  • Cellular level hypersensitivity to ionizing
    radiation and chromosomal instability.

9
ATM Gene
  • A large gene 150 kb, 66 exons, 13 kb
    transcript.
  • More than 200 mutations have been defined.
  • ATM protein C-terminus is highly similar to PI-3
    kinase - plays a role in cell cycle progression
    and DNA damage response.

IR
ATM
Stops cell cycle for DNA repair.
10
AT
  • Incidence 1 in 40,000
  • No treatment / cure
  • Carriers 1 in 100
  • No diagnosis for carrier status
  • Increased risk for cancers, breast cancers

11
CURRENT STATUS
  • Diagnosis very inadequate
  • Treatment none
  • Prevention none (of progression and
    development of malignancies)
  • We know the disease causing gene!!

12
TOOLS DNA MICROARRAYS
  • Survey thousands ( 30,000) of genes for their
    relative abundance.
  • Technology and reagents are readily available.

RNA AT pts RNA normal
..
..
..
13
METHODS
AT/-
NL
RNA RNA RNA
scan and analyze data
14
DX by Molecular Fingerprint
  • Find genes that allow us to identify AT carriers
    use microarrays to screen for genes
    differentially expressed between carriers and
    normal controls.
  • Results AT carrier compared to normal,
  • 10 genes increased 2 fold
  • 3 genes decreased 2 fold

15
Differentially expressed genes between AT
carriers and normal controls
16
TREATMENT
  • First, identify all the cellular pathways
    involved with the disease.
  • Then, select the ones that are potential targets
    for intervention.

17
Identification of the IR-response pathway
IR
Identify the genes that are differentially expres
sed explain why AT cells are so susceptible to
IR.
Expression profile at 2, 6, 12, 24 hours post
irradiation.
AT
IR
NL
18
Principal Components Analysis of the Gene
Expression Data
19
Normal
AT
12 Hr
2 Hr
2 Hr
6 Hr
20
Differentially expressed genes that are most
correlated with the first component.
21
PREVENTION
  • Disease, progression, and complications
  • Map susceptibility genes
  • Positional cloning
  • Direct IBD Mapping
  • others

22
CONCLUSION
  • Shape medical research by combining genetics and
    genomics to improve the care of patients through
    development of tools that will improve
  • diagnosis
  • treatment
  • prevention
  • of diseases.

23
Cheung lab Kuang-Yu Jen Jason Watts Josh
Burdick Statistical analysis Richard Spielman
About PowerShow.com