Thalassaemia screening and confirmation of carriers in parents.

Haemoglobinopathies are among the most common inherited monogenic disorders worldwide. Thalassaemia screening for carrier status is recommended for adults of reproductive age if suspected of being at risk. Conventional laboratory methods for screening include the assessment of haematological indices, and high-performance liquid chromatography, capillary electrophoresis or isoelectric focusing to measure the levels of HbA2 and HbF, and to identify haemoglobin variants. Each screening method has its advantages and disadvantages, the main disadvantage being that none can fully resolve all variants. The complex nature of the genetics of haemoglobinopathies necessitates expertise in the interpretation of screening results to evaluate the most likely genotypes, which must then be confirmed using the DNA diagnosis. This review highlights the limits and pitfalls of each screening technique, and outlines a rational combination of different methods to overcome issues in thalassaemia carrier detection.

VKORC1 pharmacogenetics and pharmacoproteomics in patients on warfarin anticoagulant therapy: transthyretin precursor as a potential biomarker.

BACKGROUND: Recognizing specific protein changes in response to drug administration in humans has the potential for the development of personalized medicine. Such changes can be identified by pharmacoproteomics approach based on proteomic technologies. It can also be helpful in matching a particular target-based therapy to a particular marker in a subgroup of patients, in addition to the profile of genetic polymorphism. Warfarin is a commonly prescribed oral anticoagulant in patients with prosthetic valve disease, venous thromboembolism and stroke. METHODS AND FINDING: We used a combined pharmacogenetics and iTRAQ-coupled LC-MS/MS pharmacoproteomics approach to analyze plasma protein profiles of 53 patients, and identified significantly upregulated level of transthyretin precursor in patients receiving low dose of warfarin but not in those on high dose of warfarin. In addition, real-time RT-PCR, western blotting, human IL-6 ELISA assay were done for the results validation. CONCLUSION: This combined pharmacogenomics and pharmacoproteomics approach may be applied for other target-based therapies, in matching a particular marker in a subgroup of patients, in addition to the profile of genetic polymorphism.

Transcriptome profiling of neuronal model cell PC12 from rat pheochromocytoma.

GeneChip microarray is a cutting-edge technology being used to study the expression patterns of genes with in a particular cell type. In this study, the Affymetrix RAE230A platform was used to profile stably expressed mRNA transcripts from PC12 cells at passage 5 and 15. The whole-cell PC12 transcriptome revealed that a total of 7,531 stable transcripts (P < 0.05), corresponding to 6,785 genes, were found to be consistently expressed between passage 5 and 15. The data analysis revealed 3,080 functional proteins, belonging to 13 families, which indicate that about 65% of the proteins expressed in PC12 cells are uncharacterized. By using our custom-built rat neuronal reference genome database, we mapped endogenously expressed stable neuronal transcripts from PC12 cells comprising about 765 genes responsible for neuronal function and disease. These neuronal transcripts were further analyzed to provide a genetic blueprint that can be used by neurobiologist to unravel the complex cellular and molecular mechanisms underlying biological functions and their associated signalling networks for diseases affecting the nervous system.