3. Birth Defects (M of D, 2006)
Frequency
7.9 million/yr. 3.3 million deaths
25% comprised of 5 diseases
Congenital heart disease (1 m);
Neural tube defect (324,000);
Haemoglobinopathy (308,000);
Down syndrome (217,000);
G6PD deficiency (177,000)
Relationship to GNI
Low income 60.2%
Middle income 33.5%
High income 6.3%
3
4. Common Genetic Disorders of
Haemoglobin
Thalassaemia
thalassaemia
thalassaemia
Structural variants
Haemoglobin S
Haemoglobin E
Haemoglobin C
4
5. Annual births of severe
disorders of haemoglobin
Sickle cell anaemia
Sub-Saharan Africa 240,932
Elsewhere 92,997
HbSC disease 54,736
Thalassaemia
thalassaemia major 23,329
HbE thalassaemia 20,588
HbH disease 14,504
HbS thalassaemia 12,321
Hb Bart’s hydrops 5,183
5
6.
7.
8. Population genetics and dynamics of
genetic disease in the developing
countries
1) Natural selection
2) Consanguinity
3) Parental age
4) Population migration
5) Epidemiological transition
8
9. Organisation required for control of
thalassaemia in the developing countries
North/South and South/South
partnerships
Support by WHO, funding agencies,
NGOs, Governments
Definition of economic issues. GBD
programme
9
10. Oxford-Sri Lanka
North/South Partnership
Joint research programme
Capacity building
National Thalassaemia Centre
Central reference laboratory
Molecular Medicine Centre
National Thalassaemia Programme
Education
Screening
Staff Training in Oxford
10
13. Genomics and Control of
Haemoglobin Disorders
Prevention Screening. PND
Fetal blood/globin synthesis 1974-1989 13,921
cases
DNA Analysis by CVS 1980
Improved Management
Transfusion. Chelation. Hydroxyurea etc. 1960
Heterogeneity
‘Candidate’ genes. Linkage. Unusual phenotypes 1970
GWAS and related studies. Confirmed/extended
No new modifiers
Gene Therapy
14. Molecular Medicine (1950 - 2010)
Monogenic (Mendelian) disease
Diagnosis, prenatal diagnosis (therapy)
Communicable disease
Diagnosis, (therapy)
Cancer
Mechanisms, diagnosis, therapy
Vascular disease, diabetes, dementia, rheumatic
disease etc.
Small (multigenic) components
Pharmacogenomics
Drug design, (personalised therapy)
14
15. The Future
Data collection
Genomics. GWS
Transcriptomics
Epigenomics
Proteomics
Metabolomics
Phenomics
Analysis
Systems biology
Cellmap
15
16. The Future
Expansion of North-South partnerships
Evolution of South-South partnerships
Modification of medical education in rich
countries
Education of governments of rich countries
and NGO’s regarding cost-effectiveness of
partnerships