Displaying publications 1 - 20 of 38 in total

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  1. Fulltext Gastric precancerous lesions are associated with gene variants in Helicobacter pylori-susceptible ethnic Malays
    Maran S, Lee YY, Xu S, Rajab NS, Hasan N, Syed Abdul Aziz SH, et al.
    World J Gastroenterol, 2013 Jun 21;19(23):3615-22.
    PMID: 23801863 DOI: 10.3748/wjg.v19.i23.3615
    To identify genes associated with gastric precancerous lesions in Helicobacter pylori (H. pylori)-susceptible ethnic Malays.
  2. Fulltext A genome wide pattern of population structure and admixture in peninsular Malaysia Malays
    Hatin WI, Nur-Shafawati AR, Etemad A, Jin W, Qin P, Xu S, et al.
    Hugo J, 2014 Dec;8(1):5.
    PMID: 27090253 DOI: 10.1186/s11568-014-0005-z
    BACKGROUND: The Malays consist of various sub-ethnic groups which are believed to have different ancestral origins based on their migrations centuries ago. The sub-ethnic groups can be divided based on the region they inhabit; the northern (Melayu Kedah and Melayu Kelantan), western (Melayu Minang) and southern parts (Melayu Bugis and Melayu Jawa) of Peninsular Malaysia. We analyzed 54,794 autosomal single nucleotide polymorphisms (SNPs) which were shared by 472 unrelated individuals from 17 populations to determine the genetic structure and distributions of the ancestral genetic components in five Malay sub-ethnic groups namely Melayu Bugis, Melayu Jawa, Melayu Minang, Melayu Kedah, and Melayu Kelantan. We also have included in the analysis 12 other study populations from Thailand, Indonesia, China, India, Africa and Orang Asli sub-groups in Malay Peninsula, obtained from the Pan Asian SNP Initiative (PASNPI) Consortium and International HapMap project database.

    RESULTS: We found evidence of genetic influx from Indians to Malays, more in Melayu Kedah and Melayu Kelantan which are genetically different from the other Malay sub-ethnic groups, but similar to Thai Pattani. More than 98% of these northern Malays haplotypes could be found in either Indians or Chinese populations, indicating a highly admixture pattern among populations. Nevertheless, the ancestry lines of Malays, Indonesians and Thais were traced back to have shared a common ancestor with the Proto-Malays and Chinese.

    CONCLUSIONS: These results support genetic admixtures in the Peninsular Malaysia Malay populations and provided valuable information on the enigmatic demographical history as well as shed some insights into the origins of the Malays in the Malay Peninsula.

  3. Fulltext Dissecting the genetic structure and admixture of four geographical Malay populations
    Deng L, Hoh BP, Lu D, Saw WY, Twee-Hee Ong R, Kasturiratne A, et al.
    Sci Rep, 2015 Sep 23;5:14375.
    PMID: 26395220 DOI: 10.1038/srep14375
    The Malay people are an important ethnic composition in Southeast Asia, but their genetic make-up and population structure remain poorly studied. Here we conducted a genome-wide study of four geographical Malay populations: Peninsular Malaysian Malay (PMM), Singaporean Malay (SGM), Indonesian Malay (IDM) and Sri Lankan Malay (SLM). All the four Malay populations showed substantial admixture with multiple ancestries. We identified four major ancestral components in Malay populations: Austronesian (17%-62%), Proto-Malay (15%-31%), East Asian (4%-16%) and South Asian (3%-34%). Approximately 34% of the genetic makeup of SLM is of South Asian ancestry, resulting in its distinct genetic pattern compared with the other three Malay populations. Besides, substantial differentiation was observed between the Malay populations from the north and the south, and between those from the west and the east. In summary, this study revealed that the genetic identity of the Malays comprises a mixed entity of multiple ancestries represented by Austronesian, Proto-Malay, East Asian and South Asian, with most of the admixture events estimated to have occurred 175 to 1,500 years ago, which in turn suggests that geographical isolation and independent admixture have significantly shaped the genetic architectures and the diversity of the Malay populations.
  4. Fulltext Modification of the contact surfaces for improving the puncture resistance of laminar structures
    Wang P, Yang J, Li X, Liu M, Zhang X, Sun D, et al.
    Sci Rep, 2017 07 26;7(1):6615.
    PMID: 28747656 DOI: 10.1038/s41598-017-06007-3
    Uncovering energy absorption and surface effects of various penetrating velocities on laminar structures is essential for designing protective structures. In this study, both quasi-static and dynamic penetration tests were systematical conducted on the front surfaces of metal sheets coated with a graphene oxide (GO) solution and other media. The addition of a GO fluid film to the front impact surface aided in increasing the penetration strength, improving the failure extension and dissipating additional energy under a wide-range of indentation velocity, from 3.33 × 10-5 m/s to 4.42 m/s. The coated -surfaces improved the specific energy dissipation by approximately 15~40% relative to the dry-contact configuration for both single-layer and double-layer configurations, and specific energy dissipations of double-layer configurations were 20~30% higher than those of the single-layer configurations. This treatment provides a facile strategy in changing the contact state for improving the failure load and dissipate additional energy.
  5. Fulltext Effect of Academic Self-Efficacy on Test Anxiety of Higher Vocational College Students: The Chain Mediating Effect
    Jia J, Ma Y, Xu S, Zheng J, Ma X, Zhang Y, et al.
    Psychol Res Behav Manag, 2023;16:2417-2424.
    PMID: 37426390 DOI: 10.2147/PRBM.S413382
    OBJECTIVE: This study aimed to investigate the impact of academic self-efficacy on test anxiety among higher vocational students, as well as the role of sense of life meaning, fear of failure, and gender difference in mediating this relationship.

    METHODS: A total of 2231 higher vocational students from Shandong Province were surveyed by means of Academic Self-efficacy Questionnaire, Meaning in Life Questionnaire, and Test Anxiety Scale.

    RESULTS: There were significant negative correlations among academic self-efficacy, sense of life meaning, and test anxiety. Fear of failure was positively correlated with test anxiety. Sense of life meaning and fear of failure played a mediating role in the relationship between academic self-efficacy and test anxiety. The chain mediating effect was significant only in the female group, not in the male group. In contrast, academic self-efficacy indirectly predicted test anxiety by the independent mediating effect of sense of life meaning or fear of failure in the male group.

    CONCLUSION: Academic self-efficacy may influence test anxiety through the independent mediating effect of sense of life meaning, fear of failure, and the chain mediating effect, and there is a gender difference in these effects.

  6. Fulltext PanSNPdb: the Pan-Asian SNP genotyping database
    Ngamphiw C, Assawamakin A, Xu S, Shaw PJ, Yang JO, Ghang H, et al.
    PLoS One, 2011;6(6):e21451.
    PMID: 21731755 DOI: 10.1371/journal.pone.0021451
    The HUGO Pan-Asian SNP consortium conducted the largest survey to date of human genetic diversity among Asians by sampling 1,719 unrelated individuals among 71 populations from China, India, Indonesia, Japan, Malaysia, the Philippines, Singapore, South Korea, Taiwan, and Thailand. We have constructed a database (PanSNPdb), which contains these data and various new analyses of them. PanSNPdb is a research resource in the analysis of the population structure of Asian peoples, including linkage disequilibrium patterns, haplotype distributions, and copy number variations. Furthermore, PanSNPdb provides an interactive comparison with other SNP and CNV databases, including HapMap3, JSNP, dbSNP and DGV and thus provides a comprehensive resource of human genetic diversity. The information is accessible via a widely accepted graphical interface used in many genetic variation databases. Unrestricted access to PanSNPdb and any associated files is available at: http://www4a.biotec.or.th/PASNP.
  7. Fulltext Population genetic structure of peninsular Malaysia Malay sub-ethnic groups
    Hatin WI, Nur-Shafawati AR, Zahri MK, Xu S, Jin L, Tan SG, et al.
    PLoS One, 2011;6(4):e18312.
    PMID: 21483678 DOI: 10.1371/journal.pone.0018312
    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.
  8. Signalling pathways regulating galactosaminoglycan synthesis and structure in vascular smooth muscle: Implications for lipoprotein binding and atherosclerosis
    Afroz R, Cao Y, Rostam MA, Ta H, Xu S, Zheng W, et al.
    Pharmacol Ther, 2018 07;187:88-97.
    PMID: 29454855 DOI: 10.1016/j.pharmthera.2018.02.005
    Atherosclerosis commences with the trapping of low density lipoproteins (LDLs) in blood vessels by modified proteoglycans (PGs) with hyperelongated glycosaminoglycan (GAG) chains. GAG chain synthesis and growth factor mediated hyperelongation regulates the composition and size of PGs in a manner that would cause low density lipoprotein (LDLs) retention in vessel wall. Galactosaminoglycans are a class of GAGs, commonly observed on PGs. Multiple enzymes are involved in galactosaminoglycan biosynthesis. Galactosaminoglycan synthesis is regulated by various signalling pathways which are amenable to pharmacological manipulation to treat atherosclerosis. Receptor mediated signalling pathways including protein tyrosine kinase receptors (PTKRs), serine/threonine kinase receptors (S/TKRs) and G-protein coupled receptors (GPCRs) pathways regulate galactosaminoglycan synthesizing enzyme expression. Increased expression of these enzymes modify galactosaminoglycan chain structure by making them hyperelongated. This review focuses on the signalling pathways regulating the expression of genes involved in galactosaminoglycan synthesis and modification. Furthermore, there are multiple other processes for inhibiting the interactions between LDL and galactosaminoglycans such as peptide mimetics of ApoB100 and anti-galactosaminoglycan antibodies and the therapeutic potential of these strategies is also addressed.
  9. Fulltext Was Wuhan the early epicenter of the COVID-19 pandemic?-A critique
    Cao Y, Chen L, Chen H, Cun Y, Dai X, Du H, et al.
    Natl Sci Rev, 2023 Apr;10(4):nwac287.
    PMID: 37089192 DOI: 10.1093/nsr/nwac287
  10. Fulltext The Effect of Precursor Concentration on the Particle Size, Crystal Size, and Optical Energy Gap of CexSn1-xO2 Nanofabrication
    Al-Hada NM, Md Kasmani R, Kasim H, Al-Ghaili AM, Saleh MA, Banoqitah EM, et al.
    Nanomaterials (Basel), 2021 Aug 22;11(8).
    PMID: 34443973 DOI: 10.3390/nano11082143
    In the present work, a thermal treatment technique is applied for the synthesis of CexSn1-xO2 nanoparticles. Using this method has developed understanding of how lower and higher precursor values affect the morphology, structure, and optical properties of CexSn1-xO2 nanoparticles. CexSn1-xO2 nanoparticle synthesis involves a reaction between cerium and tin sources, namely, cerium nitrate hexahydrate and tin (II) chloride dihydrate, respectively, and the capping agent, polyvinylpyrrolidone (PVP). The findings indicate that lower x values yield smaller particle size with a higher energy band gap, while higher x values yield a larger particle size with a smaller energy band gap. Thus, products with lower x values may be suitable for antibacterial activity applications as smaller particles can diffuse through the cell wall faster, while products with higher x values may be suitable for solar cell energy applications as more electrons can be generated at larger particle sizes. The synthesized samples were profiled via a number of methods, such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). As revealed by the XRD pattern analysis, the CexSn1-xO2 nanoparticles formed after calcination reflect the cubic fluorite structure and cassiterite-type tetragonal structure of CexSn1-xO2 nanoparticles. Meanwhile, using FT-IR analysis, Ce-O and Sn-O were confirmed as the primary bonds of ready CexSn1-xO2 nanoparticle samples, whilst TEM analysis highlighted that the average particle size was in the range 6-21 nm as the precursor concentration (Ce(NO3)3·6H2O) increased from 0.00 to 1.00. Moreover, the diffuse UV-visible reflectance spectra used to determine the optical band gap based on the Kubelka-Munk equation showed that an increase in x value has caused a decrease in the energy band gap and vice versa.
  11. Fulltext Genetic Connections and Convergent Evolution of Tropical Indigenous Peoples in Asia
    Deng L, Pan Y, Wang Y, Chen H, Yuan K, Chen S, et al.
    Mol Biol Evol, 2022 Feb 03;39(2).
    PMID: 34940850 DOI: 10.1093/molbev/msab361
    Tropical indigenous peoples in Asia (TIA) attract much attention for their unique appearance, whereas their genetic history and adaptive evolution remain mysteries. We conducted a comprehensive study to characterize the genetic distinction and connection of broad geographical TIAs. Despite the diverse genetic makeup and large interarea genetic differentiation between the TIA groups, we identified a basal Asian ancestry (bASN) specifically shared by these populations. The bASN ancestry was relatively enriched in ancient Asian human genomes dated as early as ∼50,000 years before the present and diminished in more recent history. Notably, the bASN ancestry is unlikely to be derived from archaic hominins. Instead, we suggest it may be better modeled as a survived lineage of the initial peopling of Asia. Shared adaptations inherited from the ancient Asian ancestry were detected among the TIA groups (e.g., LIMS1 for hair morphology, and COL24A1 for bone formation), and they are enriched in neurological functions either at an identical locus (e.g., NKAIN3), or different loci in an identical gene (e.g., TENM4). The bASN ancestry could also have formed the substrate of the genetic architecture of the dark pigmentation observed in the TIA peoples. We hypothesize that phenotypic convergence of the dark pigmentation in TIAs could have resulted from parallel (e.g., DDB1/DAK) or genetic convergence driven by admixture (e.g., MTHFD1 and RAD18), new mutations (e.g., STK11), or notably purifying selection (e.g., MC1R). Our results provide new insights into the initial peopling of Asia and an advanced understanding of the phenotypic convergence of the TIA peoples.
  12. Fulltext Acute Marjolin's Ulcer in Chronic Foot Wounds with Previous Negative Biopsy: Report of Two Cases
    Xu S, Kang Y, Soeharno H, Yeo N
    Malays Orthop J, 2020 Nov;14(3):194-197.
    PMID: 33403086 DOI: 10.5704/MOJ.2011.033
    Marjolin's ulcer is a rare and often overlooked diagnosis which can be encountered by a variety of specialities. Majority of the literatures describe long latency period of 11 to 75 years. The authors present two unusual cases of rapid progression to Marjolin's ulcer in patients with previously negative biopsy 8- and 10-month prior. This highlights the importance for clinicians to have a high degree of suspicion when encountered with any non-healing wound, especially one who's symptomatology and morphological features have undergone an acute change. Even with previous negative biopsy, patients should still be followed-up closely and clinicians should not hesitate to perform re-biopsy if the suspicion arises.
  13. Characterisation of the mitochondrial genome and phylogenetic analysis of Toxocara apodemi (Nematoda: Ascarididae)
    Gao Y, Hu Y, Xu S, Liang H, Lin H, Yin TH, et al.
    J Helminthol, 2024 Apr 15;98:e33.
    PMID: 38618902 DOI: 10.1017/S0022149X24000221
    We first sequenced and characterised the complete mitochondrial genome of Toxocara apodeme, then studied the evolutionary relationship of the species within Toxocaridae. The complete mitochondrial genome was amplified using PCR with 14 specific primers. The mitogenome length was 14303 bp in size, including 12 PCGs (encoding 3,423 amino acids), 22 tRNAs, 2 rRNAs, and 2 NCRs, with 68.38% A+T contents. The mt genomes of T. apodemi had relatively compact structures with 11 intergenic spacers and 5 overlaps. Comparative analyses of the nucleotide sequences of complete mt genomes showed that T. apodemi had higher identities with T. canis than other congeners. A sliding window analysis of 12 PCGs among 5 Toxocara species indicated that nad4 had the highest sequence divergence, and cox1 was the least variable gene. Relative synonymous codon usage showed that UUG, ACU, CCU, CGU, and UCU most frequently occurred in the complete genomes of T. apodemi. The Ka/Ks ratio showed that all Toxocara mt genes were subject to purification selection. The largest genetic distance between T. apodemi and the other 4 congeneric species was found in nad2, and the smallest was found in cox2. Phylogenetic analyses based on the concatenated amino acid sequences of 12 PCGs demonstrated that T. apodemi formed a distinct branch and was always a sister taxon to other congeneric species. The present study determined the complete mt genome sequences of T. apodemi, which provide novel genetic markers for further studies of the taxonomy, population genetics, and systematics of the Toxocaridae nematodes.
  14. The Effects of Bacillus subtilis QST713 and β-mannanase on growth performance, intestinal barrier function, and the gut microbiota in weaned piglets
    Liu J, Ma X, Zhuo Y, Xu S, Hua L, Li J, et al.
    J Anim Sci, 2023 Jan 03;101.
    PMID: 37583344 DOI: 10.1093/jas/skad257
    We investigated the effects of different Bacillus subtilis QST713 doses and a B. subtilis QST713 and β-mannanase mix on growth performance, intestinal barrier function, and gut microbiota in weaned piglets. In total, 320 healthy piglets were randomly assigned to four groups: 1) control group (basal diet), 2) BS100 group (basal diet plus 100 mg/kg B. subtilis QST713), 3) BS200 group (basal diet plus 200 mg/kg B. subtilis QST713), and 4) a BS100XT group (basal diet plus 100 mg/kg B. subtilis QST713 and 150 mg/kg β-mannanase). The study duration was 42 d. We showed that feed intake in weaned piglets on days 1 to 21 was increased in group BS100 (P < 0.05), and that the feed conversion ratio in group BS100XT animals decreased throughout the study (P < 0.05). In terms of microbial counts, the BS100XT group showed reduced Escherichia coli and Clostridium perfringens numbers on day 21 (P < 0.05). Moreover, no significant α-diversity differences were observed across all groups during the study (P > 0.05). However, principal coordinates analysis indicated clear separations in bacterial community structures across groups (analysis of similarities: P < 0.05) on days 21 and 42. Additionally, E-cadherin, occludin, and zonula occludens-1 (ZO-1) expression in piglet feces increased (P < 0.05) by adding B. subtilis QST713 and β-mannanase to diets. Notably, this addition decreased short-chain fatty acid concentrations. In conclusion, B. subtilis QST713 addition or combined B. subtilis QST713 plus β-mannanase effectively improved growth performance, intestinal barrier function, and microbial balance in weaned piglets.
  15. Fulltext View of Pakistani Residents toward Coronavirus Disease (COVID-19) during a Rapid Outbreak: A Rapid Online Survey
    Hayat K, Rosenthal M, Xu S, Arshed M, Li P, Zhai P, et al.
    Int J Environ Res Public Health, 2020 05 12;17(10).
    PMID: 32408528 DOI: 10.3390/ijerph17103347
    BACKGROUND: Coronavirus disease (COVID-19) is a deadly disease that is affecting most of the countries worldwide. Public understanding, including knowledge about signs and symptoms, mode of transmission, and hygiene of COVID-19, is vital for designing effective control strategies during a public health crisis. The current study is aimed at investigating the public's perspective about COVID-19, including their knowledge, attitude, and practices.

    METHODS: A rapid online survey comprising 22 items was administered during the rapid outbreak of COVID-19 in Pakistan. Questions were focused on the prevention, transmission, clinical features, and control of COVID-19. In addition, the attitudes and practices of the participants were explored. Descriptive statistics, Mann-Whitney tests, Kruskal-Wallis tests, and regression analysis were carried out during data analysis.

    RESULTS: A total of 1257 respondents participated in this study. Most of the respondents had good knowledge (good = 64.8%, average = 30.5%, poor = 4.7%) of COVID-19. Gender, marital status, education, and residence were observed to have a significant association with the knowledge score. A vast majority of the survey respondents (77.0%) believed that COVID-19 would be controlled successfully in Pakistan. The practices of wearing a mask (85.8%) and handwashing (88.1%) were common among the participants.

    CONCLUSION: The participants demonstrated good knowledge and reasonable attitudes and practices toward most aspects of the COVID-19 outbreak. Improvements in certain areas could be made by mass-level education.

  16. An immune-enhanced multivalent DNA nanovaccine to prevent H7 and H9 avian influenza virus in mice
    Xu S, Lan H, Teng Q, Li X, Jin Z, Qu Y, et al.
    Int J Biol Macromol, 2023 Aug 12;251:126286.
    PMID: 37579904 DOI: 10.1016/j.ijbiomac.2023.126286
    H7 avian influenza virus has caused multiple human infections and poses a severe public health threat. In response to the highly variable nature of AIVs, a novel, easily regenerated DNA vaccine has great potential in treating or preventing avian influenza pandemics. Nevertheless, DNA vaccines have many disadvantages, such as weak immunogenicity and poor in vivo delivery. To further characterize and solve these issues and develop a novel H7 AIV DNA vaccine with enhanced stability and immunogenicity, we constructed nine AIV DNA plasmids, and the immunogenicity screened showed that mice immunized with pβH7N2SH9 elicited stronger hemagglutination-inhibiting (HI) antibodies than other eight plasmid DNAs. Then, to address the susceptibility to degradation and low transfection rate of DNA vaccine in vivo, we developed pβH7N2SH9/DGL NPs by encapsulating the pβH7N2SH9 within the dendrigraft poly-l-lysines nanoparticles. As expected, these NPs exhibited excellent physical and chemical properties, were capable of promote lymphocyte proliferation, and induce stronger humoral and cellular responses than the naked pβH7N2SH9, including higher levels of HI antibodies than naked pβH7N2SH9, as well as the production of cytokines, namely, IL-2, IFN-α. Taken together, our results suggest that the construction of an immune-enhanced H7-AIV DNA nanovaccine may be a promising strategy against most influenza viruses.
  17. Influence of starch silylation on the structures and properties of starch/epoxidized soybean oil-based bioplastics
    Yang J, Xu S, Chee CY, Ching KY, Wei Y, Wang R, et al.
    Int J Biol Macromol, 2024 Feb;258(Pt 2):129037.
    PMID: 38158061 DOI: 10.1016/j.ijbiomac.2023.129037
    The present work systematically investigated the influence of starch silylation on the structures and properties of starch/epoxidized soybean oil-based bioplastics. Silylated starch was synthesized using starch particles (SP-ST) or gelatinized starch (SG-ST) under different silane hydrolysis pHs. Due to the appearance of -NH2 groups and lower OH wavenumbers, SP-ST obtained at pH 5 showed higher silylation degree and stronger hydrogen bond interaction with epoxidized soybean oils (ESO) than that at pH 11. The morphology analysis revealed better interfacial compatibility of ESO and SP-ST. The tensile strength of the samples containing SP-ST increased by 51.91 % than the control, emphasizing the enhanced interaction within the bioplastics. However, tensile strength of the bioplastics with SG-ST decreased by 59.56 % due to their high moisture contents from unreacted silanes. Additionally, the bioplastics with SG-ST exhibited an obvious reduction of thermal stability and an increase in water solubility because of the presence of unreacted APMS. The bioplastic degradation was not prevented by starch silylation except high pH. The bioplastics showed the most desirable tensile properties, thermal stability, and water solubility when starch was surface-modified with silanes hydrolyzed at pH 5. These outcomes made the fabricated bioplastics strong candidates for petroleum-based plastics for packaging applications.
  18. Fulltext Fine-scale population structure of Malays in Peninsular Malaysia and Singapore and implications for association studies
    Hoh BP, Deng L, Julia-Ashazila MJ, Zuraihan Z, Nur-Hasnah M, Nur-Shafawati AR, et al.
    Hum Genomics, 2015 Jul 22;9:16.
    PMID: 26194999 DOI: 10.1186/s40246-015-0039-x
    Fine scale population structure of Malays - the major population in Malaysia, has not been well studied. This may have important implications for both evolutionary and medical studies. Here, we investigated the population sub-structure of Malay involving 431 samples collected from all states from peninsular Malaysia and Singapore. We identified two major clusters of individuals corresponding to the north and south peninsular Malaysia. On an even finer scale, the genetic coordinates of the geographical Malay populations are in correlation with the latitudes (R(2) = 0.3925; P = 0.029). This finding is further supported by the pairwise FST of Malay sub-populations, of which the north and south regions showed the highest differentiation (FST [North-south] = 0.0011). The collective findings therefore suggest that population sub-structure of Malays are more heterogenous than previously expected even within a small geographical region, possibly due to factors like different genetic origins, geographical isolation, could result in spurious association as demonstrated in our analysis. We suggest that cautions should be taken during the stage of study design or interpreting the association signals in disease mapping studies which are expected to be conducted in Malay population in the near future.
  19. Genomic structure of the native inhabitants of Peninsular Malaysia and North Borneo suggests complex human population history in Southeast Asia
    Yew CW, Lu D, Deng L, Wong LP, Ong RT, Lu Y, et al.
    Hum Genet, 2018 Feb;137(2):161-173.
    PMID: 29383489 DOI: 10.1007/s00439-018-1869-0
    Southeast Asia (SEA) is enriched with a complex history of peopling. Malaysia, which is located at the crossroads of SEA, has been recognized as one of the hubs for early human migration. To unravel the genomic complexity of the native inhabitants of Malaysia, we sequenced 12 samples from 3 indigenous populations from Peninsular Malaysia and 4 native populations from North Borneo to a high coverage of 28-37×. We showed that the Negritos from Peninsular Malaysia shared a common ancestor with the East Asians, but exhibited some level of gene flow from South Asia, while the North Borneo populations exhibited closer genetic affinity towards East Asians than the Malays. The analysis of time of divergence suggested that ancestors of Negrito were the earliest settlers in the Malay Peninsula, whom first separated from the Papuans ~ 50-33 thousand years ago (kya), followed by East Asian (~ 40-15 kya), while the divergence time frame between North Borneo and East Asia populations predates the Austronesian expansion period implies a possible pre-Neolithic colonization. Substantial Neanderthal ancestry was confirmed in our genomes, as was observed in other East Asians. However, no significant difference was observed, in terms of the proportion of Denisovan gene flow into these native inhabitants from Malaysia. Judging from the similar amount of introgression in the Southeast Asians and East Asians, our findings suggest that the Denisovan gene flow may have occurred before the divergence of these populations and that the shared similarities are likely an ancestral component.
  20. The population genomic landscape of human genetic structure, admixture history and local adaptation in Peninsular Malaysia
    Deng L, Hoh BP, Lu D, Fu R, Phipps ME, Li S, et al.
    Hum Genet, 2014 Sep;133(9):1169-85.
    PMID: 24916469 DOI: 10.1007/s00439-014-1459-8
    Peninsular Malaysia is a strategic region which might have played an important role in the initial peopling and subsequent human migrations in Asia. However, the genetic diversity and history of human populations--especially indigenous populations--inhabiting this area remain poorly understood. Here, we conducted a genome-wide study using over 900,000 single nucleotide polymorphisms (SNPs) in four major Malaysian ethnic groups (MEGs; Malay, Proto-Malay, Senoi and Negrito), and made comparisons of 17 world-wide populations. Our data revealed that Peninsular Malaysia has greater genetic diversity corresponding to its role as a contact zone of both early and recent human migrations in Asia. However, each single Orang Asli (indigenous) group was less diverse with a smaller effective population size (N(e)) than a European or an East Asian population, indicating a substantial isolation of some duration for these groups. All four MEGs were genetically more similar to Asian populations than to other continental groups, and the divergence time between MEGs and East Asian populations (12,000--6,000 years ago) was also much shorter than that between East Asians and Europeans. Thus, Malaysian Orang Asli groups, despite their significantly different features, may share a common origin with the other Asian groups. Nevertheless, we identified traces of recent gene flow from non-Asians to MEGs. Finally, natural selection signatures were detected in a batch of genes associated with immune response, human height, skin pigmentation, hair and facial morphology and blood pressure in MEGs. Notable examples include SYN3 which is associated with human height in all Orang Asli groups, a height-related gene (PNPT1) and two blood pressure-related genes (CDH13 and PAX5) in Negritos. We conclude that a long isolation period, subsequent gene flow and local adaptations have jointly shaped the genetic architectures of MEGs, and this study provides insight into the peopling and human migration history in Southeast Asia.
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