Population Genetic Structure of Peninsular Malaysia Malay Sub-Ethnic Groups

Patterns of modern human population structure are helpful in understanding the history of human migration and admixture. We conducted a study on genetic structure of the Malay population in Malaysia, using 54,794 genome-wide single nucleotide polymorphism genotype data generated in four Malay sub-ethnic groups in peninsular Malaysia (Melayu Kelantan, Melayu Minang, Melayu Jawa and Melayu Bugis). To the best of our knowledge this is the first study conducted on these four Malay sub-ethnic groups and the analysis of genotype data of these four groups were compiled together with 11 other populations' genotype data from Indonesia, China, India, Africa and indigenous populations in Peninsular Malaysia obtained from the Pan-Asian SNP database. The phylogeny of populations showed that all of the four Malay sub-ethnic groups are separated into at least three different clusters. The Melayu Jawa, Melayu Bugis and Melayu Minang have a very close genetic relationship with Indonesian populations indicating a common ancestral history, while the Melayu Kelantan formed a distinct group on the tree indicating that they are genetically different from the other Malay sub-ethnic groups. We have detected genetic structuring among the Malay populations and this could possibly be accounted for by their different historical origins. Our results provide information of the genetic differentiation between these populations and a valuable insight into the origins of the Malay sub-ethnic groups in Peninsular Malaysia

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

The first Malay database toward the ethnic-specific target molecular variation

BACKGROUND:The Malaysian Node of the Human Variome Project (MyHVP) is one of the eighteen official Human Variome Project (HVP) country-specific nodes. Since its inception in 9(th) October 2010, MyHVP has attracted the significant number of Malaysian clinicians and researchers to participate and contribute their data to this project. MyHVP also act as the center of coordination for genotypic and phenotypic variation studies of the Malaysian population. A specialized database was developed to store and manage the data based on genetic variations which also associated with health and disease of Malaysian ethnic groups. This ethnic-specific database is called the Malaysian Node of the Human Variome Project database (MyHVPDb). FINDINGS:Currently, MyHVPDb provides only information about the genetic variations and mutations found in the Malays. In the near future, it will expand for the other Malaysian ethnics as well. The data sets are specified based on diseases or genetic mutation types which have three main subcategories: Single Nucleotide Polymorphism (SNP), Copy Number Variation (CNV) followed by the mutations which code for the common diseases among Malaysians. MyHVPDb has been open to the local researchers, academicians and students through the registration at the portal of MyHVP ( http://hvpmalaysia.kk.usm.my/mhgvc/index.php?id=register ). CONCLUSIONS:This database would be useful for clinicians and researchers who are interested in doing a study on genomics population and genetic diseases in order to obtain up-to-date and accurate information regarding the population-specific variations and also useful for those in countries with similar ethnic background

Identification of Close Relatives in the HUGO Pan-Asian SNP Database

The HUGO Pan-Asian SNP Consortium has recently released a genome-wide dataset, which consists of 1,719 DNA samples collected from 71 Asian populations. For studies of human population genetics such as genetic structure and migration history, this provided the most comprehensive large-scale survey of genetic variation to date in East and Southeast Asia. However, although considered in the analysis, close relatives were not clearly reported in the original paper. Here we performed a systematic analysis of genetic relationships among individuals from the Pan-Asian SNP (PASNP) database and identified 3 pairs of monozygotic twins or duplicate samples, 100 pairs of first-degree and 161 second-degree of relationships. Three standardized subsets with different levels of unrelated individuals were suggested here for future applications of the samples in most types of population-genetics studies (denoted by PASNP1716, PASNP1640 and PASNP1583 respectively) based on the relationships inferred in this study. In addition, we provided gender information for PASNP samples, which were not included in the original dataset, based on analysis of X chromosome data

THE USE OF SNPS IN PHARMACOGENOMICS STUDIES

Pharmacogenomics is the study of how genetic makeup determines the response to a therapeutic intervention. It has the potential to revolutionize the practice of medicine by individualisation of treatment through the use of novel diagnostic tools . This new science should reduce the trial-and-error approach to the choice of treatment and thereby limit the exposure of patients to drugs that are not effective or are toxic for them. Single Nucleotide Polymorphisms (SNPs) holds the key in defining the risk of an individual'or Linkage disequilibrium (LD) mapping approaches. Concerns about the required patient sample sizes, the extent of LD, the number of SNPs needed in a map, the cost of genotyping SNPs, and the interpretation of results are some of the challenges that surround this field. While LD mapping is appealing in that it is an unbiased approach and allows a comprehensive genome-wide survey, the challenges and limitations are significant. An alternative such as the candidate gene approach does offer several advantages over LD mapping. Ultimately, as all human genes are discovered, the need for random SNP markers diminishes and gene-based SNP approaches will predominate. The challenges will then be to demonstrate convincing links between genetic variation and drug responses and to translate that information into useful pharmacogenomic test

Cytogenetics: Past, present and future

Fifty years have elapsed since the discovery of the number of human chromosomes in 1956. Newer techniques have been developed since then, ranging from the initial conventional banding techniques to the currently used molecular array comparative genomic hybridisation. With a combination of these conventional and molecular techniques, cytogenetics has become an indispensable tool for the diagnosis of various genetic disorders, paving the way for possible treatment and management. This paper traces the history and evolution of cytogenetics leading up to the current state of technology

Peninsular Malaysia’s Negrito orang Asli and its theory of African origin

Negritos of Peninsular Malaysia have physical features which strongly resemble the African pygmies rather than any of the other main South East Asian ethnic groups. In addition, their features are also completely different from the two other large sub-groups of the Peninsular Malaysia Orang Asli, i.e. Senoi and Proto-Malay. In this study, we genetically screened three African-specific markers, Glucose-6 Phosphate Dehydrogenase (G6PD) gene PvuII Type 2 polymorphism and A- mutation; and Sickle Cell trait in 103 unrelated individuals with G6PD deficiency. None of the Negritos’ samples carried A- and Sickle cell mutations but all males and females have the PvuII Type 2 polymorphism. The same results were seen in all DNA samples of the Malaysian’s Malay, Chinese and Indians. Additionally, all females in this study were homozygous for PvuII Type 2 polymorphism. Thus, we concluded that this polymorphism is widespread in all Malaysian population and is not unique to just Africans. However, these findings indicated that the polymorphism was widely conserved and can be used to study the African descendant in any world population hitherto supporting the ‘Out of Africa’ theory

Yusof Z. Lipid profile parameters in Malaysian dyslipidemic patients. The Kobe journal of the medical sciences

ABSTRACT Introduction The importance of serum lipids as cardiovascular risk factors is well recognized. However, most published studies have focused on western countries. The present study aimed to describe and analyze the lipid profile parameters in Malaysian dyslipidemic patients, and to identify concomitant clinical problems and risk factors associated with cardiovascular disease (CVD) among such patients. Methods: A retrospective record review was carried out at Hospital Universiti Sains Malaysia.The records were reviewed for 890 dyslipidemic patients who attended the hospital in 2007. Data were collected for age at time of presentation, sex, ethnicity, smoking status, pre-treatment lipid levels, and presence of associated illnesses. The study sample was classified according to the National Cholesterol Education Program Adult Treatment Panel III risk groups. Results: The mean (SD) values for total cholesterol, low-density lipoprotein cholesterol, high density lipoprotein cholesterol, and triglycerides were 6.4 (1.3), 4.1 (1.3), 1.4 (0.5) and 1.9 (1.2) mmol/l, respectively. Less than half of study sample (43.1%) had coronary heart disease and coronary heart diseases equivalents, 24.3% were at moderate risk, and 32.6% were at low risk. Hypertension was present in 79.9% of the study sample, while 27.5% were diabetics. Cardiovascular disease was reported among 17.9%. Logistic regression revealed that family history of premature cardiovascular disease, higher age risk group; ethnicity and total cholesterol were predictors for the development of cardiovascular disease. Conclusion: The present review showed that dyslipidemic patients had high total cholesterol levels, according to National Cholesterol Education Program Adult Treatment Panel III guidelines. They were clinically diagnosed at middle age. Hypertension and diabetes Phone: +6019-9875767 Fax: +609-7676922 E-mail: [email protected] E38 LIPID PROFILES IN MALAYSIAN DYSLIPIDEMIC PATIENTS were the commonest associated clinical problems. A large proportion of the patients were within the coronary heart disease or coronary heart disease risk equivalent group. Family history of premature cardiovascular disease, age, ethnicity, and total cholesterol are important risk factors for the development of cardiovascular disease in Malaysian dyslipidemic patients