Displaying publications 1 - 20 of 27 in total

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  1. Zain SM, Mohamed R, Mahadeva S, Cheah PL, Rampal S, Basu RC, et al.
    Hum Genet, 2012 Jul;131(7):1145-52.
    PMID: 22258181 DOI: 10.1007/s00439-012-1141-y
    The adiponutrin (PNPLA3) rs738409 polymorphism has been found to be associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in various cohorts. We further investigated the association of this polymorphism with non-alcoholic steatohepatitis (NASH) severity and with histological features of NAFLD. A total of 144 biopsy-proven NAFLD patients and 198 controls were genotyped for PNPLA3 gene polymorphism (rs738409 C>G). The biopsy specimens were histologically graded by a qualified pathologist. We observed an association of G allele with susceptibility to NAFLD in the pooled subjects (OR 2.34, 95% CI 1.69-3.24, p < 0.0001), and following stratification, in each of the three ethnic subgroups, namely Chinese, Indian and Malay (OR 1.94, 95% CI 1.12-3.37, p = 0.018; OR 3.51, 95% CI 1.69-7.26, p = 0.001 and OR 2.05, 95% CI 1.25-3.35, p = 0.005, respectively). The G allele is associated with susceptibility to NASH (OR 2.64, 95% CI 1.85-3.75, p < 0.0001), with NASH severity (OR 1.85, 95% CI 1.05-3.26, p = 0.035) and with presence of fibrosis (OR 1.95, 95% CI 1.17-3.26, p = 0.013) but not with simple steatosis nor with other histological parameters. Although the serum triglyceride level is significantly higher in NAFLD patients compared to controls, the G allele is associated with decreased level of triglycerides (p = 0.029) in the NAFLD patients. Overall, the rs738409 G allele is associated with severity of NASH and occurrence of fibrosis in patients with NAFLD.
  2. Yong RY, Gan LS, Chang YM, Yap EP
    Hum Genet, 2007 Nov;122(3-4):237-49.
    PMID: 17588179
    Amelogenin paralogs on Chromosome X (AMELX) and Y (AMELY) are commonly used sexing markers. Interstitial deletion of Yp involving the AMELY locus has previously been reported. The combined frequency of the AMELY null allele in Singapore and Malaysia populations is 2.7%, 0.6% in Indian and Malay ethnic groups respectively. It is absent among 541 Chinese screened. The null allele in this study belongs to 3 Y haplogroups; J2e1 (85.7%), F* (9.5%) and D* (4.8%). Low and high-resolution STS mapping, followed by sequence analysis of breakpoint junction confirmed a large deletion of 3 to 3.7-Mb located at the Yp11.2 region. Both breakpoints were located in TSPY repeat arrays, suggesting a non-allelic homologous recombination (NAHR) mechanism of deletion. All regional null samples shared identical breakpoint sequences according to their haplogroup affiliation, providing molecular evidence of a common ancestry origin for each haplogroup, and at least 3 independent deletion events recurred in history. The estimated ages based on Y-SNP and STR analysis were approximately 13.5 +/- 3.1 kyears and approximately 0.9 +/- 0.9 kyears for the J2e1 and F* mutations, respectively. A novel polymorphism G > A at Y-GATA-H4 locus in complete linkage disequilibrium with J2e1 null mutations is a more recent event. This work re-emphasizes the need to include other sexing markers for gender determination in certain regional populations. The frequency difference among global populations suggests it constitutes another structural variation locus of human chromosome Y. The breakpoint sequences provide further information to a better understanding of the NAHR mechanism and DNA rearrangements due to higher order genomic architecture.
  3. 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.
  4. Teng YS, Jehan S, Lie-Injo LE
    Hum Genet, 1979;53(1):87-90.
    PMID: 395099
    Human alcohol dehydrogenase ADH2 and ADH3 were investigated in liver and stomach specimens of Chinese and Indians from West Malaysia. Eight-nine percent of the Chinese carry the atypical ADH2 type, a proportion very similar to that reported in Japanese. However, among 43 Indian specimens there was not a single case of atypical ADH2. In Indians, the gene frequency of ADH13 is 0.64 and of ADH23 0.36, similar to the frequencies in Caucasians, whereas in Chinese, the gene frequency for ADH13 and ADH23 is 0.91 and 0.09, respectively. We also report some unusual enzymatic characteristics in the course of our study.
  5. Teng YS, Tan SG, Lopez CG, Ng T, Lie-Injo LE
    Hum Genet, 1978 Apr 24;41(3):347-54.
    PMID: 649160
    Malaysians of Malay, Chinese, and Indian ancestries were electrophoretically phenotyped for Amy1 and saliva esterase region 1 (Set-1) from saliva, Amy2 from plasma, soluble and mitochondrial GOT and PGM3 from leukocyte and placenta. Kadazans and Bajaus, the indigenous people of Sabah, East Malaysia were surveyed for Amy2. Three types of variants were observed for Amy1, one type for Amy2. Only Indians were found to be polymorphic for Amy1. Two GOTs 2-1 and three GOTm 2-1 variants were found among 281 Chinese while three GOTm 2-1 variants were found among 311 Malays. Malaysian Malays, Chinese, and Indians were found to be polymorphic for Set-1 and PGM3. The gene frequencies in Malays are Set-1F=0.601 +/- 0.021, Set-1S = 0.399 +/- 0.021; PGM13 = 0.788 +/- 0.020, PGM23 = 0.212 +/- 0.020; in Chinese Set-1F = 0.497 +/- 0.028, Set-1S = 0.503 +/- 0.028; PGM13 = 0.745 +/- 0.24, PGM23 = 0.255 +/- 0.024; in Indians, Set-1F = 0.449 +/- 0.031, Set-1S = 0.551 +/- 0.031; PGM13 = 0.755 +/- 0.029, PGM23 = 0.245 +/- 0.029.
  6. Teng YS, Lie-Ingo LE
    Hum Genet, 1977 Apr 15;36(2):231-4.
    PMID: 870415
    A rare electrophoretic variant of superoxide dismutase (SOD) was found in one Filipino of 146 Filipinos, 1382 Malaysians and 816 Indonesians examined. The variant consists of two usual bands and two slower migrating bands similar to those reported earlier. Superoxide dismutase variants are common among people of certain localized regions in Europe, however, this is the first report of such a variant occurring in people of non-European origin.
  7. Teh BT, Hii SI, David R, Parameswaran V, Grimmond S, Walters MK, et al.
    Hum Genet, 1994 Nov;94(5):468-72.
    PMID: 7959678 DOI: 10.1007/bf00211009
    Multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disease characterized by neoplasia of the parathyroid glands, anterior pituitary and endocrine pancreas, is rarely reported in Asian populations. The MEN1 gene, mapped to chromosome 11q13 but yet to be cloned, has been found to be homogeneous in Caucasian populations through linkage analysis. Here, two previously unreported Asian kindreds with MEN1 are described; linkage analysis using microsatellite polymorphic markers in the MEN1 region was carried out. The first kindred, of Mongolian-Chinese origin, is a multigeneration family with over 150 living members, eight of whom are affected to date. The second kindred is of Chinese origin consisting of four affected members. Linkage to chromosome 11q13 was confirmed in both kindreds, supporting evidence for genetic homogeneity. A recombination in the larger kindred localizes the gene distal to marker D11S956, consistent with its placement from previous studies. We also show that it is feasible to use these markers for predictive testing, as four gene carriers were detected in 13 family members with unknown disease status in the first kindred.
  8. Tan SG, Teng YS, Ganesan J, Lau KY, Lie-Injo LE
    Hum Genet, 1979 Jul 18;49(3):349-53.
    PMID: 289626
    Kadazans, the largest indigenous group in Sabah, northern Borneo, were surveyed for glyoxalase I, phosphoglucomutase I, red cell acid phosphatase, esterase D, adenosine deaminase, soluble glutamate pyruvate transaminase, soluble glutamate oxaloacetate transaminase, 6-phosphogluconate dehydrogenase, uridine monophosphate kinase, adenylate kinase, peptidase B and D, superoxide dismutase, C5, group specific component, haptoglobin and transferrin. Kadazans were found to be polymorphic for GLO I, PGM I, RCAP, esterase D, ADA, s-Gpt, 6PGD, UMPK, Gc, C5, haptoglobin and peptidase B. Rare variants were found for transferrin and peptidase D. No variant was found for s-Got, SOD and AK.
  9. Tan SG, Gan YY, Asuan K
    Hum Genet, 1982;60(4):369-70.
    PMID: 7106773
    Malays, Chinese, and Indians from Peninsular Malaysia; Ibans and Bidayuh from Sarawak State; Kadazans from Sabah State, Northern Borneo; and Bataks, Minangkabau, and Javanese from North Sumatra, Indonesia, were subtyped for transferrin C by polyacrylamide gel isoelectric focusing. All nine populations studied are polymorphic for two alleles, TfCl and TfC2, TfC3 was polymorphic in six populations and present as a rare variant in the other three. The frequency of TfC1 ranged from 0.855 in Bidayuh to 0.711 in Javanese, that of TfC2 from 0.231 in Indians to 0.113 in Bidayuh, and that of TfC3 from 0.030 in Javanese and Chinese to 0.008 in Bidayuh. TfDchi is polymorphic in all the populations that we studied except in Minangkabau, in whom it is present as a rare variant, and in Indians, in whom it is absent.
  10. Tan SG, Gan YY, Asuan K, Abdullah F
    Hum Genet, 1981;59(1):75-6.
    PMID: 10819027
    Malays, Chinese and Indians from peninsular Malaysia; Ibans and Bidayuh from Sarawak state, Northern Borneo; and Bataks, Minangkabau and Javanese from North Sumatra, Indonesia, were subtyped for Gc (group-specific component) by polyacrylamide gel isoelectric focusing. All eight populations investigated were found to be polymorphic for three common alleles, Gc1F, Gc1S and Gc2.
  11. Tan LP, Ng BK, Balraj P, Poh BH, Lim PK, Peh SC
    Hum Genet, 2005 Dec;118(3-4):539-40.
    PMID: 16521263
  12. Tan JH, Low PS, Tan YS, Tong MC, Saha N, Yang H, et al.
    Hum Genet, 2003 Jul;113(2):106-17.
    PMID: 12709788
    Mutations in the ATP-binding cassette transporter ABCA1 underlie Tangier disease and familial hypoalphaliproteinemia (FHA), disorders that are characterised by reduced high-density lipoprotein-cholesterol (HDL-C) concentration and cholesterol efflux, and increased coronary artery disease (CAD). We explored if polymorphisms in the ABCA1 gene are associated with CAD and variations in plasma lipid levels, especially HDL-C, and whether the associations may depend on ethnicity. Male cases and controls from the Singapore Chinese, Malay and Indian populations were genotyped for five ABCA1 single nucleotide polymorphisms. Various single-locus frequency distribution differences between cases and controls were detected in different ethnic groups: the promoter -14C>T in Indians, exon 18 M883I in Malays, and 3'-untranslated (UTR) region 8994A>G in Chinese. For the Malay population, certain haplotypes carrying the I825- A (exon 17) and M883- G alleles were more frequent among cases than controls, whereas the converse was true for the alternative configuration of V825- G and I883- A, and this association was reinforced in multi-locus disequilibrium analysis that utilized genotypic data. In the healthy controls, associations were found for -14C>T genotypes with HDL-C in Chinese; 237indelG (5'UTR) with apolipoprotein A1 (apoA1) in Malays and total cholesterol (TC) in Indians; M883I with lipoprotein(a) [Lp(a)] in Malays and apolipoprotein B (apoB) in Chinese; and 8994A>G with Lp(a) in Malays, and TC, low-density lipoprotein-cholesterol (LDL-C) as well as apoB in Indians. While genotype-phenotype associations were not reproduced across populations and loci, V825I and M883I were clearly associated with CAD status in Malays with no effects on HDL-C or apoA1.
  13. Soares PA, Trejaut JA, Rito T, Cavadas B, Hill C, Eng KK, et al.
    Hum Genet, 2016 Mar;135(3):309-26.
    PMID: 26781090 DOI: 10.1007/s00439-015-1620-z
    There are two very different interpretations of the prehistory of Island Southeast Asia (ISEA), with genetic evidence invoked in support of both. The "out-of-Taiwan" model proposes a major Late Holocene expansion of Neolithic Austronesian speakers from Taiwan. An alternative, proposing that Late Glacial/postglacial sea-level rises triggered largely autochthonous dispersals, accounts for some otherwise enigmatic genetic patterns, but fails to explain the Austronesian language dispersal. Combining mitochondrial DNA (mtDNA), Y-chromosome and genome-wide data, we performed the most comprehensive analysis of the region to date, obtaining highly consistent results across all three systems and allowing us to reconcile the models. We infer a primarily common ancestry for Taiwan/ISEA populations established before the Neolithic, but also detected clear signals of two minor Late Holocene migrations, probably representing Neolithic input from both Mainland Southeast Asia and South China, via Taiwan. This latter may therefore have mediated the Austronesian language dispersal, implying small-scale migration and language shift rather than large-scale expansion.
  14. Shi W, Massaia A, Louzada S, Banerjee R, Hallast P, Chen Y, et al.
    Hum Genet, 2018 Jan;137(1):73-83.
    PMID: 29209947 DOI: 10.1007/s00439-017-1857-9
    We describe the variation in copy number of a ~ 10 kb region overlapping the long intergenic noncoding RNA (lincRNA) gene, TTTY22, within the IR3 inverted repeat on the short arm of the human Y chromosome, leading to individuals with 0-3 copies of this region in the general population. Variation of this CNV is common, with 266 individuals having 0 copies, 943 (including the reference sequence) having 1, 23 having 2 copies, and two having 3 copies, and was validated by breakpoint PCR, fibre-FISH, and 10× Genomics Chromium linked-read sequencing in subsets of 1234 individuals from the 1000 Genomes Project. Mapping the changes in copy number to the phylogeny of these Y chromosomes previously established by the Project identified at least 20 mutational events, and investigation of flanking paralogous sequence variants showed that the mutations involved flanking sequences in 18 of these, and could extend over > 30 kb of DNA. While either gene conversion or double crossover between misaligned sister chromatids could formally explain the 0-2 copy events, gene conversion is the more likely mechanism, and these events include the longest non-allelic gene conversion reported thus far. Chromosomes with three copies of this CNV have arisen just once in our data set via another mechanism: duplication of 420 kb that places the third copy 230 kb proximal to the existing proximal copy. Our results establish gene conversion as a previously under-appreciated mechanism of generating copy number changes in humans and reveal the exceptionally large size of the conversion events that can occur.
  15. Sandholzer C, Hallman DM, Saha N, Sigurdsson G, Lackner C, Császár A, et al.
    Hum Genet, 1991 Apr;86(6):607-14.
    PMID: 2026424
    Apolipoprotein(a) [apo(a)] exhibits a genetic size polymorphism explaining about 40% of the variability in lipoprotein(a) [Lp(a)] concentration in Tyroleans. Lp(a) concentrations and apo(a) phenotypes were determined in 7 ethnic groups (Tyrolean, Icelandic, Hungarian, Malay, Chinese, Indian, Black Sudanese) and the effects of the apo(a) size polymorphism on Lp(a) levels were estimated in each group. Average Lp(a) concentrations were highly significantly different among these populations, with the Chinese (7.0 mg/dl) having the lowest and the Sudanese (46 mg/dl) the highest levels. Apo(a) phenotype and derived apo(a) allele frequencies were also significantly different among the populations. Apo(a) isoform effects on Lp(a) levels were not significantly different among populations. Lp(a) levels were however roughly twice as high in the same phenotypes in the Indians, and several times as high in the Sudanese, compared with Caucasians. The size variation of apo(a) explains from 0.77 (Malays) to only 0.19 (Sudanese) of the total variability in Lp(a) levels. Together these data show (I) that there is considerable heterogeneity of the Lp(a) polymorphism among populations, (II) that differences in apo(a) allele frequencies alone do not explain the differences in Lp(a) levels among populations and (III) that in some populations, e.g. Sudanese Blacks, Lp(a) levels are mainly determined by factors that are different from the apo(a) size polymorphism.
  16. Noraini I, Tan SG, Gan YY, Teng YS
    Hum Genet, 1980;56(2):205-7.
    PMID: 7450777
    Three human saliva genetic markers, namely, salivary peroxidase (SAPX), Pm, and Ph proteins, were investigated in the three major ethnic groups of Malaysia: Malays, Chinese, and Indians. For Pm, the allelic frequencies of Pm+ for Malays, Chinese, and Indians are 0.385 +/- 0.030, 0.282 +/- 0.026, and 0.289 +/- 0.026 respectively. For Ph, the allelic frequencies of Ph+ are 0.082 +/- 0.016 for Malays, 0.109 +/- 0.017 for Chinese, and 0.062 +/- 0.013 for Indians. For SAPX, the allelic frequencies of SAPX1 in Malays, Chinese, and Indians are 0.762 +/- 0.027, 0.755 +/- 0.027, and 0.723 +/- 0.026 respectively.
  17. Liu X, Yunus Y, Lu D, Aghakhanian F, Saw WY, Deng L, et al.
    Hum Genet, 2015 Apr;134(4):375-92.
    PMID: 25634076 DOI: 10.1007/s00439-014-1525-2
    The indigenous populations from Peninsular Malaysia, locally known as Orang Asli, continue to adopt an agro-subsistence nomadic lifestyle, residing primarily within natural jungle habitats. Leading a hunter-gatherer lifestyle in a tropical jungle environment, the Orang Asli are routinely exposed to malaria. Here we surveyed the genetic architecture of individuals from four Orang Asli tribes with high-density genotyping across more than 2.5 million polymorphisms. These tribes reside in different geographical locations in Peninsular Malaysia and belong to three main ethno-linguistic groups, where there is minimal interaction between the tribes. We first dissect the genetic diversity and admixture between the tribes and with neighboring urban populations. Later, by implementing five metrics, we investigated the genome-wide signatures for positive natural selection of these Orang Asli, respectively. Finally, we searched for evidence of genomic adaptation to the pressure of malaria infection. We observed that different evolutionary responses might have emerged in the different Orang Asli communities to mitigate malaria infection.
  18. Lie-Injo LE, Pawson IG, Solai A
    Hum Genet, 1985;70(2):116-8.
    PMID: 2989152
    Most of the population in certain areas of Melanesia have one alpha-globin gene deletion (alpha thal2). It is thought that the high frequencies of alpha thal2 in this population is due to a selective advantage given by malaria infection to carriers of alpha thal2. We are interested in neighboring Polynesia which, although adjacent to Melanesia, has always been free of malaria due to the absence of the vector anopheles. We studied 60 Polynesian Samoans and 150 Malaysians by restriction endonuclease gene mapping using Eco RI, Bam HI, and Bgl II and hybridization to 32P-labeled alpha-globin gene probe. Seven among the 60 (11.7%) Samoans had triplicated alpha-globin loci type 1, while none had alpha thal2. On digestion with Bgl II the third alpha-globin gene was found in an additional 3.7 kb fragment in all seven Samoans with triplicated alpha-globin loci, while digestion with Bam HI produced an abnormal elongated 18.2 kb fragment carrying alpha-globin genes in addition to the normal 14.5 kb fragment. None of the Polynesian Samoans had alpha thal2 or alpha thal1. Only two of the Malaysians had triplicated alpha-globin loci.
  19. Iwai K, Hirono A, Matsuoka H, Kawamoto F, Horie T, Lin K, et al.
    Hum Genet, 2001 Jun;108(6):445-9.
    PMID: 11499668
    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a heterogeneous enzyme abnormality with high frequency in tropical areas. We performed population screening and molecular studies of G6PD variants to clarify their distribution and features in Southeast Asia. A total of 4317 participants (2019 males, 2298 females) from 16 ethnic groups in Myanmar, Lao in Laos, and Amboinese in Indonesia were screened with a single-step screening method. The prevalence of G6PD-deficient males ranged from 0% (the Akha) to 10.8% (the Shan). These G6PD-deficient individuals and 12 G6PD-deficient patients who had been diagnosed at hospitals in Indonesia and Malaysia were subjected to molecular analysis by a combination of polymerase-chain-reaction-based single-strand conformation polymorphism analysis and direct sequencing. Ten different missense mutations were identified in 63 G6PD-deficient individuals (50 hemizygotes, 11 heterozygotes, and 2 homozygotes) from 14 ethnic groups. One missense mutation (1291 G-->A) found in an Indonesian Chinese, viz., G6PD Surabaya, was previously unknown. The 487 G-->A (G6PD Mahidol) mutation was widely seen in Myanmar, 383 T-->C (G6PD Vanua Lava) was specifically found among Amboinese, 871 G-->A (G6PD Viangchan) was observed mainly in Lao, and 592 C-->T (G6PD Coimbra) was found in Malaysian aborigines (Orang Asli). The other five mutations, 95 A-->G (G6PD Gaohe), 1003 G-->A (G6PD Chatham), 1360 C-->T (G6PD Union), 1376 G-->T (G6PD Canton), and 1388 G-->A (G6PD Kaiping) were identified mostly in accordance with distributions reported previously.
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