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Fulltext Sri Petaling COVID-19 cluster in Malaysia: challenges and the mitigation strategies

Safuan S, Edinur HA

Acta Biomed, 2020 11 10;91(4):e2020154.
PMID: 33525245 DOI: 10.23750/abm.v91i4.10345

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Reconstruction of the Austronesian Diaspora in the Era of Genomics

Chambers GK, Edinur HA

Hum Biol, 2021 10;92(4):247-263.
PMID: 34665569 DOI: 10.13110/humanbiology.92.4.04

The Austronesian Diaspora is a 5,000-year account of how a small group of Taiwanese farmers expanded to occupy territories reaching halfway around the world. Reconstructing their detailed history has spawned many academic contests across many disciplines. An outline orthodox version has eventually emerged but still leaves many unanswered questions. The remarkable power of whole-genome technology has now been applied to people across the entire region. This review gives an account of this era of genetic investigation and discusses its many achievements, including revelation in detail of many unexpected patterns of population movement and the significance of this information for medical genetics.
Fulltext Compendium of hand, foot and mouth disease data in Malaysia from years 2010-2017

Nelson BR, Edinur HA, Abdullah MT

Data Brief, 2019 Jun;24:103868.
PMID: 30976640 DOI: 10.1016/j.dib.2019.103868

This data article is constructed using information from hand, foot and mouth disease outbreaks in every Malaysian state. Important information like total number of cases from every state and age group, humidity, air temperature and wind as well as types of viruses isolated from patients infected with hand, foot and mouth disease were gathered and sorted into four tables. The information sources include Malaysian Administrative Modernisation and Management Planning Unit (MAMPU), National Centre for Biotechnology Information (NCBI) and National Oceanic and Atmospheric Administration (NOAA). Since the Ministry of Health Malaysia only begun archiving hand, foot and mouth disease cases between years 2010-2017 in MAMPU, weather data extractions are following the similar timeline. Conversely, published data on viruses and their serotypes associated to hand, foot and mouth disease were extracted from NCBI but, data availability were limited between the years 2010 and 2014.
The genetic history of Peninsular Malaysia

Norhalifah HK, Syaza FH, Chambers GK, Edinur HA

Gene, 2016 Jul 15;586(1):129-35.
PMID: 27060406 DOI: 10.1016/j.gene.2016.04.008

This article explores the genetic history of the various sub-populations currently living in Peninsular Malaysia. This region has received multiple waves of migrants like the Orang Asli in prehistoric times and the Chinese, Indians, Europeans and Arabs during historic times. There are three highly distinct lineages that make up the Orang Asli; Semang, Senoi and Proto-Malays. The Semang, who have 'Negrito' characteristics, represent the first human settlers in Peninsular Malaysia arriving from about 50,000ya. The Senoi later migrated from Indochina and are a mix between an Asian Neolithic population and the Semang. These Asian genomes probably came in before Austroasiatic languages arrived between 5000 and 4000years ago. Semang and Senoi both now speak Austro-Asiatic languages indicative of cultural diffusion from Senoi to Semang. In contrast, the Proto-Malays who came last to the southern part of this region speak Austronesian language and are Austronesians with some Negrito admixture. It is from this group that the contemporary Malays emerged. Here we provide an overview of the best available genetic evidences (single nucleotide polymorphisms, mitochondrial DNA, Y-chromosome, blood groups, human platelet antigen, human leukocyte antigen, human neutrophil antigen and killer-cell immunoglobulin-like receptor) supporting the complex genetic history of Peninsular Malaysia. Large scale sampling and high throughput genetic screening programmes such as those using genome-wide single nucleotide polymorphism analyses have provided insights into various ancestral and admixture genetic fractions in this region. Given the now extensive admixture present in the contemporary descendants of ancient sub-populations in Peninsular Malaysia, improved reconstruction of human migration history in this region will require new evidence from ancient DNA in well-preserved skeletons. All other aspects of the highly diverse and complex genetic makeup in Peninsular Malaysia should be considered carefully for genetic mapping of disease loci and policy formation by health authorities.
HNA diversity in six subgroups of Orang Asli in Peninsular Malaysia

Manaf SM, Panneerchelvam S, Norazmi MN, Zafarina Z, Edinur HA

Transfus Med, 2016 May 16.
PMID: 27197082 DOI: 10.1111/tme.12315
Fulltext Recent Developments in Transplantation and Transfusion Medicine

Edinur HA, Chambers GK, Dunn PP

Ann. Transplant., 2015;20:424-9.
PMID: 26218888 DOI: 10.12659/AOT.894003

Transplantation and transfusion are related and clinically important areas of multidisciplinary expertise, including pre-operative treatment, donor recruitment, tissue matching, and post-operative care. We have seen significant developments in these areas, especially in the late 20th and early 21st century. This paper reviews the latest advances in modern transplantation and transfusion medicine, including several new genetic markers (e.g., major histocompatibility complex class I chain-related gene A, killer cell immunoglobulin-like receptor, and human platelet antigens) for donor and recipient matching, genotyping platforms (e.g., next-generation sequencer and Luminex technology), donor recruitment strategies, and several clinical applications in which genotyping has advantages over agglutination tests (e.g., genotyping of weakly expressed antigens and determination of blood groups and human leukocyte antigen types in multi-transfused patients). We also highlight the roles of population studies and international collaborations in moving towards more efficient donor recruitment strategies.
Distribution of cytokine gene polymorphisms in five Malay subethnic groups in Peninsular Malaysia

Norhalifah HK, Zafarina Z, Sundararajulu P, Norazmi MN, Edinur HA

Int. J. Immunogenet., 2015 Jun;42(3):200-3.
PMID: 25809422 DOI: 10.1111/iji.12189

In this survey, we have successfully genotyped 22 single nucleotide polymorphisms in the 13 cytokine genes for five Malay subethnic groups (Kelantan, Acheh, Mandailing, Minangkabau and Patani Malays) using polymerase chain reaction-sequence-specific primer cytokine genotyping kit (Invitrogen, Carlsbad, CA, USA). Most of the cytokine genes showed similar pattern of allelic spectra with wild-type alleles (e.g. ILIa-889/C, ILIB+3962/C and IL6 nt565/G) that represent more than 80% in the studied Malay subethnic groups. These newly observed cytokine alleles and subsequent analyses clearly indicate genetic contribution from Asia in the studied Malay subethnic groups with evidence of admixture from neighbouring populations in Patani Malays. The cytokine data sets for the five Malay subethnic groups deposited in this report can also be used as reference standard for searching suitable donor for allograft transplant and diseases association study. This is particularly relevance as our analyses showed differences between the Malay subethnic groups and other populations screened for cytokine genes.
Fulltext Genetic barriers in transplantation medicine

Edinur HA, Manaf SM, Che Mat NF

World J Transplant, 2016 Sep 24;6(3):532-41.
PMID: 27683631 DOI: 10.5500/wjt.v6.i3.532

The successful of transplantation is determined by the shared human leukocyte antigens (HLAs) and ABO blood group antigens between donor and recipient. In recent years, killer cell receptor [i.e., killer cell immunoglobulin-like receptor (KIR)] and major histocompatibility complex (MHC) class I chain-related gene molecule (i.e., MICA) were also reported as important determinants of transplant compatibility. At present, several different genotyping techniques (e.g., sequence specific primer and sequence based typing) can be used to characterize blood group, HLA, MICA and KIR and loci. These molecular techniques have several advantages because they do not depend on the availability of anti-sera, cellular expression and have greater specificity and accuracy compared with the antibody-antigen based typing. Nonetheless, these molecular techniques have limited capability to capture increasing number of markers which have been demonstrated to determine donor and recipient compatibility. It is now possible to genotype multiple markers and to the extent of a complete sequencing of the human genome using next generation sequencer (NGS). This high throughput genotyping platform has been tested for HLA, and it is expected that NGS will be used to simultaneously genotype a large number of clinically relevant transplantation genes in near future. This is not far from reality due to the bioinformatics support given by the immunogenetics community and the rigorous improvement in NGS methodology. In addition, new developments in immune tolerance based therapy, donor recruitment strategies and bioengineering are expected to provide significant advances in the field of transplantation medicine.
Editorial: Biofilms: multi-species community interactions

Joshi SJ, Ray RR, Erlich GD, Edinur HA

Front Microbiol, 2023;14:1191406.
PMID: 37303794 DOI: 10.3389/fmicb.2023.1191406
Fulltext Ethnicity-based classifications and medical genetics: One Health approaches from a Western Pacific perspective

Edinur HA, Mat-Ghani SNA, Chambers GK

Front Genet, 2022;13:970549.
PMID: 36147511 DOI: 10.3389/fgene.2022.970549

A new era presently dawns for medical genetics featuring individualised whole genome sequencing and promising personalised medical genetics. Accordingly, we direct readers attention to the continuing value of allele frequency data from Genome-Wide Association Surveys (GWAS) and single gene surveys in well-defined ethnic populations as a guide for best practice in diagnosis, therapy, and prescription. Supporting evidence is drawn from our experiences working with Austronesian volunteer subjects across the Western Pacific. In general, these studies show that their gene pool has been shaped by natural selection and become highly diverged from those of Europeans and Asians. These uniquely evolved patterns of genetic variation underlie contrasting schedules of disease incidence and drug response. Thus, recognition of historical bonds of kinship among Austronesian population groups across the Asia Pacific has distinct public health advantages from a One Health perspective. Other than diseases that are common among them like gout and diabetes, Austronesian populations face a wide range of climate-dependent infectious diseases including vector-borne pathogens as they are now scattered across the Pacific and Indian Oceans. However, we caution that the value of genetic survey data in Austronesians (and other groups too) is critically dependent on the accuracy of attached descriptive information in associated metadata, including ethnicity and admixture.
Killer immunoglobulin-like receptor diversity in Malay subethnic groups of Peninsular Malaysia

NurWaliyuddin HZ, Edinur HA, Norazmi MN, Sundararajulu P, Chambers GK, Zafarina Z

Int. J. Immunogenet., 2014 Dec;41(6):472-9.
PMID: 25367623 DOI: 10.1111/iji.12161

The KIR system shows variation at both gene content and allelic level across individual genome and populations. This variation reflects its role in immunity and has become a significant tool for population comparisons. In this study, we investigate KIR gene content in 120 unrelated individuals from the four Malay subethnic groups (Kelantan, Jawa, Banjar and Pattani Malays). Genotyping using commercial polymerase chain reaction-sequence-specific primer (PCR-SSP) kits revealed a total of 34 different KIR genotypes; 17 for Kelantan, 15 for Banjar, 14 for Jawa and 13 for Pattani Malays. Two new variants observed in Banjar Malays have not previously been reported. Genotype AA and haplotype A were the most common in Jawa (0.47 and 0.65, respectively), Banjar (0.37 and 0.52, respectively) and Pattani (0.40 and 0.60, respectively) Malays. In contrast, Kelantan Malays were observed to have slightly higher frequency (0.43) of genotype BB as compared with the others. Based on the KIR genes distribution, Jawa, Pattani and Banjar subethnic groups showed greater similarity and are discrete from Kelantan Malays. A principal component plot carried out using KIR gene carrier frequency shows that the four Malay subethnic groups are clustered together with other South-East Asian populations. Overall, our observation on prevalence of KIR gene content demonstrates genetic affinities between the four Malay subethnic groups and supports the common origins of the Austronesian-speaking people.
HLA polymorphism in six Malay subethnic groups in Malaysia

Edinur HA, Zafarina Z, Spínola H, Nurhaslindawaty AR, Panneerchelvam S, Norazmi MN

Hum Immunol, 2009 Jul;70(7):518-26.
PMID: 19364514 DOI: 10.1016/j.humimm.2009.04.003

In this study, human leukocyte antigen (HLA) class I and II were examined through sequence-specific primer typing in 176 unrelated individuals from six Malay subethnic groups of Peninsular Malaysia: Kelantan (n = 25), Minangkabau (34), Jawa (30), Bugis (31), Banjar (33), and Rawa (23). The most common HLA alleles in all groups were A*24 (26-41%), Cw*07 (24-32%), B*15 (22-30%), DRB1*12 (15-36%), and DQB1*03 (25-51%). The Malay subethnic groups studied demonstrated a close relationship to each other and to other Asian populations, despite specific differences between them. Banjar, Bugis, and Jawa Malays demonstrated no significant difference from each other, which could be a result of their related origin from the islands around the Java Sea. These three Malay subethnic groups were then collapsed into one group, which also helped to increase the sample number and sharpen statistical results. Minangkabau and Rawa Malays exhibited high similarities in allele group and haplotype frequencies, which could be a consequence of their common origin from Sumatera. Kelantan Malays, in addition to their statistically significant differences compared with the other groups, also exhibited differences on the most frequent haplotypes, which are almost absent in the other subethnic groups studied.
Fulltext Ancient Genetic Signatures of Orang Asli Revealed by Killer Immunoglobulin-Like Receptor Gene Polymorphisms

NurWaliyuddin HZ, Norazmi MN, Edinur HA, Chambers GK, Panneerchelvam S, Zafarina Z

PLoS One, 2015;10(11):e0141536.
PMID: 26565719 DOI: 10.1371/journal.pone.0141536

The aboriginal populations of Peninsular Malaysia, also known as Orang Asli (OA), comprise three major groups; Semang, Senoi and Proto-Malays. Here, we analyzed for the first time KIR gene polymorphisms for 167 OA individuals, including those from four smallest OA subgroups (Che Wong, Orang Kanaq, Lanoh and Kensiu) using polymerase chain reaction-sequence specific primer (PCR-SSP) analyses. The observed distribution of KIR profiles of OA is heterogenous; Haplotype B is the most frequent in the Semang subgroups (especially Batek) while Haplotype A is the most common type in the Senoi. The Semang subgroups were clustered together with the Africans, Indians, Papuans and Australian Aborigines in a principal component analysis (PCA) plot and shared many common genotypes (AB6, BB71, BB73 and BB159) observed in these other populations. Given that these populations also display high frequencies of Haplotype B, it is interesting to speculate that Haplotype B may be generally more frequent in ancient populations. In contrast, the two Senoi subgroups, Che Wong and Semai are displaced toward Southeast Asian and African populations in the PCA scatter plot, respectively. Orang Kanaq, the smallest and the most endangered of all OA subgroups, has lost some degree of genetic variation, as shown by their relatively high frequency of the AB2 genotype (0.73) and a total absence of KIR2DL2 and KIR2DS2 genes. Orang Kanaq tradition that strictly prohibits intermarriage with outsiders seems to have posed a serious threat to their survival. This present survey is a demonstration of the value of KIR polymorphisms in elucidating genetic relationships among human populations.
Distribution of HLA-A, -B and -DRB1 alleles in the Kensiu and Semai Orang Asli sub-groups in Peninsular Malaysia

Tasnim AR, Allia S, Edinur HA, Panneerchelvam S, Zafarina Z, Norazmi MN

Hum Immunol, 2016 Aug;77(8):618-619.
PMID: 27296326 DOI: 10.1016/j.humimm.2016.06.009

The earliest settlers in Peninsular Malaysia are the Orang Asli population, namely Semang, Senoi and Proto Malays. In the present study, we typed the HLA-A, -B and -DRB1 loci of the Kensiu and Semai Orang Asli sub-groups. Sequence-based HLA typing was performed on 59 individuals from two Orang Asli sub-groups. A total of 11, 18 and 14 HLA-A, -B and -DRB1 alleles were identified, respectively. These data are available in the Allele Frequencies Net Database under the population name "Malaysia Kedah Kensiu" and "Malaysia Pahang Semai".
Distribution of cytokine gene polymorphisms in six Orang Asli subgroups in Peninsular Malaysia

Norhalifah HK, Syafawati WU, Che Mat NF, Chambers GK, Edinur HA

Hum Immunol, 2016 Apr;77(4):338-9.
PMID: 26820937 DOI: 10.1016/j.humimm.2016.01.015

Cytokines are involved in immune responses and the pathogenesis of various diseases. Allelic variations within the genes coding for various ∼30kDa cytokine protein/glycoproteins have been reported for many populations and have been the subjects of many ancestry and health analyses. In this study, we typed 22 single nucleotide polymorphisms (SNPs) in 13 cytokine genes of 165 Orang Asli individuals by using sequence specific primer-polymerase chain reaction (SSP-PCR) assay. The volunteers came from all across the Peninsular of Malaysia and belong to six Orang Asli subgroups; Batek, Kensiu, Lanoh, Che Wong, Semai and Orang Kanaq. Here we report our general findings and original genotype data and their associated analyses (Hardy-Weinberg proportions, estimation of allele and haplotype frequencies) can be found in the supplementary files and will be held at Allele Frequency Net Database (AFND).
Allele frequencies of human platelet antigens in Banjar, Bugis, Champa, Jawa and Kelantan Malays in Peninsular Malaysia

Wan Syafawati WU, Norhalifah HK, Zefarina Z, Zafarina Z, Panneerchelvam S, Norazmi MN, et al.

Transfus Med, 2015 Oct;25(5):326-32.
PMID: 26132409 DOI: 10.1111/tme.12220

The major aims of this study are to characterise and compile allelic data of human platelet antigen (HPA)-1 to -6 and -15 systems in five Malay sub-ethnic groups in Peninsular Malaysia.
Molecular blood group typing in Banjar, Jawa, Mandailing and Kelantan Malays in Peninsular Malaysia

Abd Gani R, Manaf SM, Zafarina Z, Panneerchelvam S, Chambers GK, Norazmi MN, et al.

Transfus Apher Sci, 2015 Aug;53(1):69-73.
PMID: 25819336 DOI: 10.1016/j.transci.2015.03.009

In this study we genotyped ABO, Rhesus, Kell, Kidd and Duffy blood group loci in DNA samples from 120 unrelated individuals representing four Malay subethnic groups living in Peninsular Malaysia (Banjar: n = 30, Jawa: n = 30, Mandailing: n = 30 and Kelantan: n = 30). Analyses were performed using commercial polymerase chain reaction-sequence specific primer (PCR-SSP) typing kits (BAG Health Care GmbH, Lich, Germany). Overall, the present study has successfully compiled blood group datasets for the four Malay subethnic groups and used the datasets for studying ancestry and health.
Fulltext The Prevalence of Transfusion-transmitted Infections among Blood Donors in Hospital Universiti Sains Malaysia

Ramli M, Zulkafli Z, Chambers GK, Zilan RSAR, Edinur HA

Oman Med J, 2020 Nov;35(6):e189.
PMID: 33110633 DOI: 10.5001/omj.2020.86

Objectives: Blood bank centers routinely screen for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) to ensure the safety of blood supply and thus prevent the dissemination of these viruses via blood transfusion. We sought to evaluate the detection of transfusion-transmitted infection (TTI) markers using standard serological methods and nucleic acid testing (NAT) among blood donors in Hospital Universiti Sains Malaysia.
Methods: Donated blood units were assessed for the presence or absence of HBV, HCV, and HIV using two screening method: serology and NAT. Reactive blood samples were then subjected to serological confirmatory and NAT discriminatory assays.
Results: A total of 9669 donors were recruited from September 2017 to June 2018. Among these, 36 donors were reactive either for HBV, HCV, or HIV by serological testing and eight by NAT screening. However, only 10 (three for HBV and seven for HCV) donors tested positive using serological testing and five (two for HBV and three for HCV) by NAT discriminatory assays. Note that all five NAT positive donors detected in the NAT discriminatory assays were confirmed to be serologically reactive. Therefore, the prevalence of HBV, HCV, and HIV was 0.03%, 0.1%, and 0.0%, respectively, in our donor pool.
Conclusions: Both serological and NAT screening and confirmatory assays should be used routinely to reduce the risk of infection transmission via the transfusion of blood and blood components.
Sequence polymorphisms of mtDNA HV1, HV2, and HV3 regions in the Malay population of Peninsular Malaysia

Nur Haslindawaty AR, Panneerchelvam S, Edinur HA, Norazmi MN, Zafarina Z

Int J Legal Med, 2010 Sep;124(5):415-26.
PMID: 20502908 DOI: 10.1007/s00414-010-0469-x

The uniparentally inherited mitochondrial DNA (mtDNA) is in the limelight for the past two decades, in studies relating to demographic history of mankind and in forensic kinship testing. In this study, human mtDNA hypervariable segments 1, 2, and 3 (HV1, HV2, and HV3) were analyzed in 248 unrelated Malay individuals in Peninsular Malaysia. Combined analyses of HV1, HV2, and HV3 revealed a total of 180 mtDNA haplotypes with 149 unique haplotypes and 31 haplotypes occurring in more than one individual. The genetic diversity was estimated to be 99.47%, and the probability of any two individuals sharing the same mtDNA haplotype was 0.93%. The most frequent mtDNA haplotype (73, 146, 150, 195, 263, 315.1C, 16140, 16182C, 16183C, 16189, 16217, 16274, and 16335) was shared by 11 (4.44%) individuals. The nucleotide diversity and mean of pair-wise differences were found to be 0.036063 ± 0.020101 and 12.544022 ± 6.230486, respectively.
Fulltext Human Leukocyte Antigen (HLA) class I and II datasets for sudanese

Dafalla AM, Edinur HA, Abdelwahed M, Elemam AA, Ibrahim AA, Mohamadani A, et al.

Data Brief, 2019 Jun;24:104027.
PMID: 31193964 DOI: 10.1016/j.dib.2019.104027

Sudan is located in the heart of Africa and surrounded by eight countries with people of different ethnic origins. Historical records show that the population of the Sudan is a mixture of Arabic, West Asian Arabic and sub-Saharan African elements. The present survey provides data on allele lineages, and haplotype frequencies of Human Leukocyte Antigen (HLA) class I (HLA-A and HLA-B) and class II (HLA-DR and -HLA-DQ) loci in 11 Sudanese populations. The sampled individuals are all local transplant donors who provided informed consent for HLA analyses on their blood samples and were registered at National Cancer Institute, University of Gezira, Wad Medani. The HLA class I and II data reported here can be subjected for future analyses of genetic structure and health in Sudan. These include as reference datasets for identifying the association between HLA and diseases and for designing donor recruitment strategies.

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