Haematological and molecular characterisation of high haemoglobin F among anaemic patients in Hospital Universiti Sains Malaysia

Anaemia is a condition usually associated with variety of diseases. In normal adults, haemoglobin F (HbF) levels are usually less than 1.0%. There are several genetic loci that have significant influence on HbF levels. The aim of this study is to determine the association between elevated HbF level with haematological parameters and the presence of the BCL11A (rs1186868) and HMIP-2 (rs9376090) SNPs in anaemic patients due to acquired causes. This study involved 144 anaemic patients from Hospital Universiti Sains Malaysia (HUSM) with HbF level > 1.0%. High-performance liquid chromatography (HPLC) was used to determine the HbF and HbA2 levels. Multiplex ARMS-PCR and gap-PCR were performed for those samples with high HbA2 level (>3.2%) and normal HbA2 level (≤3.2%) respectively to detect mutation at β-globin gene cluster. Allelic discrimination for rs1186868 and rs9376090 were performed using real-time PCR technique for samples with no mutation detected. In this study, the mean age of patients is 19.99 ± 1.64 years with female 61.1% predominance. Majority were Malays (99.3%). There was a moderate negative correlation and statistically significant between HbF level with Hb level and RBC count, (r = -0.348, P < 0.05) (r = -0.377, P < 0.05) respectively. Meanwhile, the correlation between HbF level with MCV and MCH showed weak negative correlation but not statistically significant, (r = -0.079, P > 0.05) (r = -0.073, P > 0.05) respectively. Following multiplex ARMS-PCR, 65 (74.7%) mutations were detected which comprises of 49 heterozygous Cd 26 (75.4%), 10 heterozygous Cd 41/42 (15.4%), 3 compound heterozygous Cd 26 and Cd 41/42 (4.6%) and 3 heterozygous IVS 1–1 (4.6%), while 22 patients were not detected. Out of 57 samples, only one patient (1.8%) was found positive with Thai (δβ)°-thalassaemia type deletions when subjected to the multiplex gap-PCR consisted of four target deletions; Siriraj J Gγ(Aγδβ)o-thal, Thai (δβ)°-thalassaemia, HPFH-6, and Hb Lepore. There was a significant difference between the mean of HbF level of patients with and without β-globin gene cluster mutation and deletion (P < 0.05). The minor allele frequency (MAF) in both rs1186868 and rs9376090 shows similar to the East Asian (EAS) population. There is no significant difference of HbF level between genotypes containing HbF-promoting alleles of rs9376090 (TC and CC) when compared to genotype TT (P > 0.05). In conclusion, HbF level correlates with anaemic status of the subjects. Elevated HbF levels showed associations with both inherited and acquired causes. Additionally, there is no relationship between the increased HbF levels with the presence of SNPs rs9376090-C among acquired anaemic patients. Despite the need for further research in this area, this study provides data that can be used as a guideline for better anaemia treatment and management

Global Globin Network Consensus Paper: Classification and Stratified Roadmaps for Improved Thalassaemia Care and Prevention in 32 Countries

The Global Globin Network (GGN) is a project-wide initiative of the Human Variome/Global Variome Project (HVP) focusing on haemoglobinopathies to build the capacity for genomic diagnosis, clinical services, and research in low- and middle-income countries. At present, there is no framework to evaluate the improvement of care, treatment, and prevention of thalassaemia and other haemoglobinopathies globally, despite thalassaemia being one of the most common monogenic diseases worldwide. Here, we propose a universally applicable system for evaluating and grouping countries based on qualitative indicators according to the quality of care, treatment, and prevention of haemoglobinopathies. We also apply this system to GGN countries as proof of principle. To this end, qualitative indicators were extracted from the IthaMaps database of the ITHANET portal, which allowed four groups of countries (A, B, C, and D) to be defined based on major qualitative indicators, supported by minor qualitative indicators for countries with limited resource settings and by the overall haemoglobinopathy carrier frequency for the target countries of immigration. The proposed rubrics and accumulative scores will help analyse the performance and improvement of care, treatment, and prevention of haemoglobinopathies in the GGN and beyond. Our proposed criteria complement future data collection from GGN countries to help monitor the quality of services for haemoglobinopathies, provide ongoing estimates for services and epidemiology in GGN countries, and note the contribution of the GGN to a local and global reduction of disease burden

Population genetics and human health in the genomic era

Population genetic data collected from variable regions in human genome have been extensively used for studying human origins and migration patterns, estimating the probative value of DNA evidence and in disease association studies. Here, we illustrate the value of population genetic data in the genomic era with an emphasis on their role in health science and practice. This commentary is intended to show the value of an ethnicity-based approach to medicine and the role of genetics via accumulated population genetic data as its rational support basis. For this specific reason, we feel that new genome-based knowledge and resources need to be disseminated urgently to health professionals, researchers, policy makers and the public, so that it may be fully integrated into health-related policy and decision making. Ideally, all population genetic databases should be freely accessible, but this creates several technical issues which need to be properly considered. Those highlighted here include such as factors sample size, marker type, population descriptions and genotyping coverage

Global Globin Network Consensus Paper: Classification and Stratified Roadmaps for Improved Thalassaemia Care and Prevention in 32 Countries

The Global Globin Network (GGN) is a project-wide initiative of the Human Variome/Global Variome Project (HVP) focusing on haemoglobinopathies to build the capacity for genomic diagnosis, clinical services, and research in low- and middle-income countries. At present, there is no framework to evaluate the improvement of care, treatment, and prevention of thalassaemia and other haemoglobinopathies globally, despite thalassaemia being one of the most common monogenic diseases worldwide. Here, we propose a universally applicable system for evaluating and grouping countries based on qualitative indicators according to the quality of care, treatment, and prevention of haemoglobinopathies. We also apply this system to GGN countries as proof of principle. To this end, qualitative indicators were extracted from the IthaMaps database of the ITHANET portal, which allowed four groups of countries (A, B, C, and D) to be defined based on major qualitative indicators, supported by minor qualitative indicators for countries with limited resource settings and by the overall haemoglobinopathy carrier frequency for the target countries of immigration. The proposed rubrics and accumulative scores will help analyse the performance and improvement of care, treatment, and prevention of haemoglobinopathies in the GGN and beyond. Our proposed criteria complement future data collection from GGN countries to help monitor the quality of services for haemoglobinopathies, provide ongoing estimates for services and epidemiology in GGN countries, and note the contribution of the GGN to a local and global reduction of disease burden