Molecular Diagnostics - PowerPoint PPT Presentation

1 / 60
About This Presentation
Title:

Molecular Diagnostics

Description:

Molecular Diagnostics : Hype or Hope ? Patrick Willems GENDIA, Antwerp, Belgium We now know how God wrote the book of life Bill Clinton But do we know how ... – PowerPoint PPT presentation

Number of Views:423
Avg rating:3.0/5.0
Slides: 61
Provided by: gendiaNet
Category:

less

Transcript and Presenter's Notes

Title: Molecular Diagnostics


1
Molecular Diagnostics Hype or Hope ? Patrick
Willems GENDIA, Antwerp, Belgium
2
(No Transcript)
3
We now know how God wrote the book of life
Bill Clinton
4
But do we know how to read the book ?
5
Genetic Diagnostics
  • Cytogenetic tests
  • FISH
  • Molecular tests

6
Molecular Diagnostics
  • Diagnosis of infectious diseases
  • Genetic identification
  • Diagnosis of genetic diseases

7
Diagnosis of infectious diseases
  • HPV
  • Chlamydia
  • Hepatitis
  • HIV
  • Toxoplasmosis

8
Genetic Identification
  • - Paternity Testing
  • - Forensics

9
Paternity Testing
10
Forensic testing

11
Diagnosis of genetic diseases
  • - Somatic rearrangements in cancer
  • - Genetic risk factors
  • Pharmacogenetics
  • - Mutations in monogenic diseases

12
Rearrangements in Cancer Cells
Chromosomal breaks produce fusion genes These
cause leukemias and lymphomas Diagnosis
determines treatment and prognosis
13
Rearrangements in Cancer Cells
  • Lymphocytic Leukemia
  • t(922) BCR - ABL
  • t(1221) TEL - AML1
  • t(119) E2A - PBX1
  • t(411) MLL - AF4
  • Myeloid Leukemia
  • Inv(16) CBF - MYH11
  • t(822) AML - ETO
  • t(922) BCR - ABL

14
Diagnosis of genetic diseases
  • - Somatic rearrangements in cancer
  • - Genetic risk factors
  • Pharmacogenetics
  • - Mutations in monogenic diseases

15
Genetic Risk Factors
  • Monogenic diseases are caused by a
  • deleterious mutation in a single gene
  • Disease-causing mutations
  • Multifactorial diseases are caused by a
  • combination of variations in multiple genes
  • Genetic Risk Factors

16
Genetic Risk Factors
  • Deep venous thrombosis
  • Cardiovascular disease
  • Alzheimer disease
  • Osteoporosis

17
Genetic Risk Factors
  • Most single risk factors
  • have NO clinical significance
  • in individual patients

18
Genetic Risk Factors
  • Deep venous thrombosis
  • Factor V
  • Factor II
  • MTHFR

19
Diagnosis of genetic diseases
  • - Somatic rearrangements in cancer
  • - Genetic risk factors
  • Pharmacogenetics
  • - Mutations in monogenic diseases

20
Pharmacogenetic tests
  • Drug specificity
  • Drug efficacity - toxicity

21
Drug specificity
  • Herceptin HER2
  • Tyrosine kinase inhibitors
  • BCR / ABL
  • KIT
  • PDGFR A/B
  • EGFR

22
Drug efficacity / toxicity
  • Cytochromes
  • CYP2D6
  • CYP2C9
  • CYP2C19

23
Diagnosis of genetic diseases
  • - Somatic rearrangements in cancer
  • - Genetic risk factors
  • Pharmacogenetics
  • - Mutations in monogenic diseases

24
Diagnostic bottle necks
  • Number of diseases
  • Nature of disease mutation
  • Technology
  • Cost
  • Number of samples
  • Organisation

25
Monogenic Diseases
  • gt 4.000 monogenic diseases
  • gt 2.000 disease genes isolated

26
Gene testing
  • Most countries limited number
  • (lt 50 genes)
  • Few countries large number
  • (300-500 genes)
  • Nowhere network complete
    availability
  • (gt 1000 genes)

27
Diagnostic bottle necks
  • Number of diseases
  • Nature of disease mutation
  • Technology
  • Cost
  • Number of samples
  • Organisation

28
Disease Mutations
  • Easy tests Single - common mutations
  • Difficult tests Private mutations

29
Disease Mutations
  • Single mutations Fragile X Sickle Cell
    Anemia
  • Common mutations Deafness Hemochromatosis
  • Panel of mutations Cystic Fibrosis
  • Private mutations Breast Cancer
  • Colorectal cancer

30
Easy tests
31
Difficult tests
32
BRCA testing
  • BRCA1 23 exonen, 1863 AA, 6.200 bp

BRCA2 28 exonen, 3418 AA, 10.300
bp Totaal gt 17.000 bp sequence
33
Diagnostic bottle necks
  • Number of diseases
  • Nature of disease mutation
  • Technology
  • Cost
  • Number of samples
  • Organisation

34
Mutation Detection
  • 1. Point mutations, frame shifts
  • A. Sequencing
  • B. WAVE
  • 2. Deletions MLPA

35
Diagnostic bottle necks
  • Number of diseases
  • Nature of disease mutation
  • Technology
  • Cost
  • Number of samples
  • Organisation

36
Cost
  • Single mutations cheap (200 E)
  • Prevalent mutations cheap (300 E)
  • Panel of mutations moderate (300 E)
  • Private mutations expensive (1000 E)

37
Cost
  • Socioeconomic situation
  • Social security
  • Reimbursement by insurance

38
Diagnostic bottle necks
  • Number of diseases
  • Nature of disease mutation
  • Technology
  • Cost
  • Number of samples
  • Organisation

39
Common Genetic Diseases
?
40
Common genetic diseases
41
Most frequent DNA tests
  • Thalassemia
  • Cystic fibrosis
  • Breast cancer
  • Colorectal cancer
  • FRAXE
  • SCA
  • F5 Leiden

42
Usual portfolio of DNA tests
  • Easy tests
  • Common tests
  • Research tests

43
Genetic testing in Europe
  • inhabitants per country 10 million
  • births per year 100.000
  • disease frequency 1 on 10.000
  • new patients per year 10
  • genetic labs 10
  • New patients per lab per year 1

44
Diagnostic bottle necks
  • Number of diseases
  • Nature of disease mutation
  • Technology
  • Cost
  • Number of samples
  • Organisation

45
Current Organisation
  • Small local labs small portfolios ( lt 50 tests
    )
  • Same spectrum of tests common easy tests
  • Majority academic labs research -diagnostic
    setting
  • Many academic labs give up diagnostic testing
  • No (inter)national network

46
Diagnostic bottle necks
  • Number of diseases
  • Nature of disease mutation
  • Technology
  • Cost
  • Number of samples
  • Organisation

47
Gene testing
  • Unreliable
  • Expensive
  • Slow

48
Unreliable

10 mistakes in easy tests such as CF
Nature Genetics 2000 25
259 - 260
49
Expensive
  • RESEARCH DIAGNOSTICS
  • 1 genome 1 gene
  • lt 1000 USD 200 5.000 USD
  • Ratio 25.000

50
Slow
  • RESEARCH DIAGNOSTICS
  • 100 genomes 1 gene
  • in 10 days in 100 days
  • Ratio 25 million

51
Message in a bottle
  • Many different tests
  • Many uncommon tests
  • Many esoteric tests
  • Many expensive tests
  • International network needed

52
Mission
  • A global network of diagnostic labs
  • Large portfolio
  • Reliable
  • Fast
  • Affordable

53
GENDIA GENetic
DIAgnostic Network
www.GENDIA.net
54
The GENDIA network
55
GENDIA Network
1000 Referral labs 1 Central lab
100 Test labs
56
Advantages GENDIA
  • 1 lab to send samples to
  • 1 lab to get results from
  • gt 2.000 genetic tests
  • Large portfolio
  • Best first selection of test
  • Best Reflex testing

57
Looking into the future

58
Next generation sequencing
Sequencing power billion bp / day Will
rapidly multiply Cost 100.000 Euros Will
rapidly decrease to 1000 Euro Whole genome
sequencing of Watson and Venter Sequencing all
patients
59
DNA Sequencing

1980-1990 1990-2005
gt 2005 Radio - gel Fluorescent -
capillary Next generation Thousand bp /
day Million bp / day
Billion bp / day
60

Write a Comment
User Comments (0)
About PowerShow.com