Short and long trainee periods

The medical problem: about 140,000 people in The Netherlands are carriers (heterozygotes) of autosomal recessive hemoglobin defects. If both parents are carriers, the combination of the defects may lead to severe forms of hemoglobinopathies (HbP's) in the children (e.g. b-thalassemia major and sickle cell disease). Only supportive treatment is for these diseases available and with the exception of the few patients that may have received a successful bone marrow transplant they usually die as young adults after a chronic history of severe pathology. The supportive therapy consists of blood transfusions and chelation therapy, prophylaxis of complications and pain treatment.

Students of Biomedical Sciences, Medicine and Laboratory technicians ("HLO") may apply for short and long trainee periods, to be concluded by a paper at the Biochemical Genetics / Hemoglobinopathies Laboratory on the following subjects.

Mutation detection
The occurrence of HbP traits is very dependant on the geographic origin of the individual. Selection mechanisms, which have favored carriers in the presence of malaria tropica in many parts of the world, have produced different spectra of mutations in the different regions. To date, more than 160 mutations inducing b-thalassemia have been characterized. In order to identify mutations it is very important to have the best possible knowledge about the mutation spectrum and frequencies in a particular population. We have characterized the mutation spectrum of the multiethnic Dutch population and the Iranian region of Hormozgan, an area with high HbP frequency. As for instance we are analyzing at this moment the occurrence of a-thalassemia in the same Iranian population using new detection methods.

Prevention-strategy
To improve HbP prevention in developing countries and in the at-risk populations of industrialized areas of Northern Europe, we are studying the possibilities of prevention strategies. We are engaged in the development, improvement, and application of fundamental and advanced biochemical, hematological, and molecular techniques for carrier detection and molecular diagnosis of HbP. Furthermore, we are studying implementation strategies and receptivity for primary prevention in different ethnic groups in The Netherlands. Surveys in which the genetic basis and clinical manifestations of HbP are explained have been applied randomly to population samples of different ethnic origin testing the degree of compliance for prenatal diagnosis.

Micro-Arrays
Beta thalassemia is mainly caused by point mutations in the relatively small b-globin gene. For this reason this gene and the related pathology present an ideal model for the development of Chip-technology and "mini-sequencing" as a mutation detection method for all kinds of genetic diseases.
We have recently started to develop this technology which is based on the detection of mutations on a microscope slide by specific recognition of the wild-type and the mutated sequences in HbP carriers.

Specific information: Dr. C.L. Harteveld
c.l.harteveld@lumc.nl