Molecular genetics of phenotypic variability in paediatric patients with Haemoglobin E/ Thalassaemia
หัวหน้าโครงการ
:
วิปร วิประกษิต
ทีมวิจัย
:
วิปร วิประกษิต
หัวหน้าโครงการ
วันที่เริ่มโครงการ
:
1 มิ.ย. 2548
วัตถุประสงค์
:
1. To describe natural history, clinical variability, disease associated complications and survival in 300 paediatric patients with Hb E/ thalassaemia
2. To determine genotype-phenotype correlation based on "hypothetical-driven approach" or "candidate gene approach" in order to find significant disease modifying genetic factors associated with;
2.1 decreased globin gene expression due to non-deletional mutation of globin genes or genetic polymorphism(s) linked to low-expression of the globin genes.
2.2 increased globin gene expression at both genetic and epigenetic control. By haplotype analysis and association study of either quantitative trait locus in cis on the globin gene cluster and in trans on chromosome 6 in the first phase of this project and in other two loci (chromosome 8 and chromosome X) in the future.
2.3 other candidate genetic modifiers based on biological data, animal model information and previous studies in other groups of thalassaemia such as AHSP, HRI (heme regulatory inhibitor), UGT1A1 and genes related to iron metabolism such as HFE, TfR 2, Hepcidin, Ferroportin and Hemojuvelin etc. These genetic modifiers will be analysed collectively using multiple regression analysis in order to identify significant modifying genes and possibly utilise as predictors for proper genetic counselling and management plan in future cases.
3. To develop a knowledge-based clinical practice guideline based on genotype-phenotype correlation data for proper genetic counselling and management plan in future cases.
