The overall objective of the laboratory core is to make diagnosis of the hemoglobin genotype available for investigators and service providers involved in research or clinical management of patients of the Comprehensive Center. Routine hemoglobin electrophoresis, quantitation of Hb A2 and F, complete blood counts, and smears for distribution of Hb F will be used to determine the genotype for most individuals who are carriers or have disease. Analysis of DNA will be made available to study individuals when the genotype is in question and to provide for prenatal diagnosis. The overall objective of this core proposal is to provide for prenatal and postnatal molecular genetic evaluations of individuals suspected to have variant hemoglobin. The specific hemoglobin variants to be evaluated include Hb S, Hb C, alpha thalassemia, and beta thalassemia. Prenatal diagnosis will be primarily developed for Hb S, Hb C, and appropriate beta thalassemia mutations. Postnatal genotyping of the specific form of alpha thalassemia will be performed to support the counseling demonstration project in a subset of patients to validate the algorithm in parents of children with Hb Bart's. Molecular genetic analysis for alpha thalassemia will enable discrimination between cis and trans forms of alpha thalassemia minor, as well as identification of the deletions or duplications of the alpha globin gene. Haplotype analysis of the beta-globin gene cluster will be provided if this proves to be valuable for identification of children who may benefit from bone marrow transplantation. Beta-globin gene cluster haplotypes in sickle cell patients are presently being evaluated in predicting severity of the clinical phenotype. This information may be effective in predicting patients who will have early and severe complications which have traditionally been treated by transfusion therapy.
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