Genomics and World Health

David WeatherallWeatherall Institute of Molecular

Medicine, University of Oxford

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Birth Defects (M of D, 2006)Frequency

7.9 million/yr. 3.3 million deaths25% 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 GNILow income 60.2%Middle income 33.5%High income 6.3%

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Common Genetic Disorders of Haemoglobin

Thalassaemia

a thalassaemia

b thalassaemia

Structural variants

Haemoglobin S

Haemoglobin E

Haemoglobin C

Annual births of severe disorders of haemoglobin

Sickle cell anaemiaSub-Saharan Africa 240,932Elsewhere 92,997

HbSC disease 54,736Thalassaemia thalassaemia major 23,329HbE thalassaemia 20,588HbH disease 14,504HbS thalassaemia 12,321Hb Bart’s hydrops 5,183

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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

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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

Oxford-Sri Lanka North/South Partnership

Joint research programmeCapacity building

National Thalassaemia CentreCentral reference laboratoryMolecular Medicine Centre

National Thalassaemia ProgrammeEducationScreening

Staff Training in Oxford

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Genomics and Control of Haemoglobin Disorders

Prevention Screening. PNDFetal blood/globin synthesis 1974-1989 13,921 casesDNA Analysis by CVS 1980

Improved ManagementTransfusion. Chelation. Hydroxyurea etc. 1960

Heterogeneity‘Candidate’ genes. Linkage. Unusual phenotypes 1970 GWAS and related studies. Confirmed/extended No new modifiers

Gene Therapy

Molecular Medicine (1950 - 2010)

Monogenic (Mendelian) diseaseDiagnosis, prenatal diagnosis (therapy)

Communicable diseaseDiagnosis, (therapy)

CancerMechanisms, diagnosis, therapy

Vascular disease, diabetes, dementia, rheumatic disease etc.

Small (multigenic) componentsPharmacogenomics

Drug design, (personalised therapy)

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The Future

Data collectionGenomics. GWSTranscriptomicsEpigenomicsProteomicsMetabolomicsPhenomics

AnalysisSystems biologyCellmap

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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