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  1. Cytogenetic and Molecular Evidence of Additional Cryptic Diversity in High Elevation Black fly Simulium feuerborni (Diptera: Simuliidae) Populations in Southeast Asia
    Pramual P, Thaijarern J, Sofian-Azirun M, Ya'cob Z, Hadi UK, Takaoka H
    J Med Entomol, 2015 Sep;52(5):829-36.
    PMID: 26336220 DOI: 10.1093/jme/tjv080
    Simulium feuerborni Edwards is geographically widespread in Southeast Asia. Previous cytogenetic study in Thailand revealed that this species is a species complex composed of two cytoforms (A and B). In this study, we cytologically examined specimens obtained from the Cameron Highlands, Malaysia, and Puncak, Java, Indonesia. The results revealed two additional cytoforms (C and D) of S. feuerborni. Specimens from Malaysia represent cytoform C, differentiated from other cytoforms by a fixed chromosome inversion on the long arm of chromosome III (IIIL-5). High frequencies of the B chromosome (33-83%) were also observed in this cytoform. Specimens from Indonesia represent the cytoform D. This cytoform is differentiated from others by a fixed chromosome inversion difference on the long arm of chromosome II (IIL-4). Mitochondrial DNA sequences support genetic differentiation among cytoforms A, B, and C. The pairwise F(ST) values among these cytoforms were highly significantly consistent with the divergent lineages of the cytoforms in a median-joining haplotype network. However, a lack of the sympatric populations prevented us from testing the species status of the cytoforms.
    Matched MeSH terms: DNA, Mitochondrial/genetics*; Simuliidae/genetics*; Insect Proteins/genetics*
  2. Fulltext Molecular cloning, sequence analysis and developmental stage expression of a putative septin gene fragment from Aedes albopictus (Diptera: Culicidae)
    Avicor SW, Wajidi MF, Jaal Z, Yahaya ZS
    Acta Biochim. Pol., 2016;63(2):243-6.
    PMID: 27059016 DOI: 10.18388/abp.2014_909
    Septins belong to GTPases that are involved in vital cellular activities, including cytokinesis. Although present in many organisms, they are yet to be isolated from Aedes albopictus. This study reports for the first time on a serendipitous isolation of a partial septin sequence from Ae. albopictus and its developmental expression profile. The Ae. albopictus partial septin sequence contains 591 nucleotides encoding 197 amino acids. It shares homology with several insect septin genes and has a close phylogenetic relationship with Aedes aegypti and Culex quinquefasciatus septins. The Ae. albopictus septin fragment was differentially expressed in the mosquito's developmental stages, with an increased expression in the adults.
    Matched MeSH terms: Aedes/genetics*; Insect Proteins/genetics*; Septins/genetics*
  3. Fulltext Sequence comparison of six human microRNAs genes between tuberculosis patients and healthy individuals
    Amila A, Acosta A, Sarmiento ME, Suraiya S, Zafarina Z, Panneerchelvam S, et al.
    Int J Mycobacteriol, 2015 Dec;4(4):341-6.
    PMID: 26964819 DOI: 10.1016/j.ijmyco.2015.06.009
    MicroRNAs (miRNAs) play an important role in diseases development. Therefore, human miRNAs may be able to inhibit the survival of Mycobacterium tuberculosis (Mtb) in the human host by targeting critical genes of the pathogen. Mutations within miRNAs can alter their target selection, thereby preventing them from inhibiting Mtb genes, thus increasing host susceptibility to the disease.
    Matched MeSH terms: Mycobacterium tuberculosis/genetics; Tuberculosis, Pulmonary/genetics*; MicroRNAs/genetics*
  4. Fulltext Diversity and Evolutionary Histories of Human Coronaviruses NL63 and 229E Associated with Acute Upper Respiratory Tract Symptoms in Kuala Lumpur, Malaysia
    Al-Khannaq MN, Ng KT, Oong XY, Pang YK, Takebe Y, Chook JB, et al.
    Am J Trop Med Hyg, 2016 05 04;94(5):1058-64.
    PMID: 26928836 DOI: 10.4269/ajtmh.15-0810
    The human alphacoronaviruses HCoV-NL63 and HCoV-229E are commonly associated with upper respiratory tract infections (URTI). Information on their molecular epidemiology and evolutionary dynamics in the tropical region of southeast Asia however is limited. Here, we analyzed the phylogenetic, temporal distribution, population history, and clinical manifestations among patients infected with HCoV-NL63 and HCoV-229E. Nasopharyngeal swabs were collected from 2,060 consenting adults presented with acute URTI symptoms in Kuala Lumpur, Malaysia, between 2012 and 2013. The presence of HCoV-NL63 and HCoV-229E was detected using multiplex polymerase chain reaction (PCR). The spike glycoprotein, nucleocapsid, and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. A total of 68/2,060 (3.3%) subjects were positive for human alphacoronavirus; HCoV-NL63 and HCoV-229E were detected in 45 (2.2%) and 23 (1.1%) patients, respectively. A peak in the number of HCoV-NL63 infections was recorded between June and October 2012. Phylogenetic inference revealed that 62.8% of HCoV-NL63 infections belonged to genotype B, 37.2% was genotype C, while all HCoV-229E sequences were clustered within group 4. Molecular dating analysis indicated that the origin of HCoV-NL63 was dated to 1921, before it diverged into genotype A (1975), genotype B (1996), and genotype C (2003). The root of the HCoV-229E tree was dated to 1955, before it diverged into groups 1-4 between the 1970s and 1990s. The study described the seasonality, molecular diversity, and evolutionary dynamics of human alphacoronavirus infections in a tropical region.
    Matched MeSH terms: Viral Proteins/genetics; Coronavirus 229E, Human/genetics*; Coronavirus NL63, Human/genetics*
  5. 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".
    Matched MeSH terms: HLA-A Antigens/genetics*; HLA-B Antigens/genetics*; HLA-DRB1 Chains/genetics*
  6. Fulltext Laboratory-Based Surveillance and Molecular Characterization of Dengue Viruses in Taiwan, 2014
    Chang SF, Yang CF, Hsu TC, Su CL, Lin CC, Shu PY
    Am J Trop Med Hyg, 2016 Apr;94(4):804-11.
    PMID: 26880779 DOI: 10.4269/ajtmh.15-0534
    We present the results of a laboratory-based surveillance of dengue in Taiwan in 2014. A total of 240 imported dengue cases were identified. The patients had arrived from 16 countries, and Malaysia, Indonesia, the Philippines, and China were the most frequent importing countries. Phylogenetic analyses showed that genotype I of dengue virus type 1 (DENV-1) and the cosmopolitan genotype of DENV-2 were the predominant DENV strains circulating in southeast Asia. The 2014 dengue epidemic was the largest ever to occur in Taiwan since World War II, and there were 15,492 laboratory-confirmed indigenous dengue cases. Phylogenetic analysis showed that the explosive dengue epidemic in southern Taiwan was caused by a DENV-1 strain of genotype I imported from Indonesia. There were several possible causes of this outbreak, including delayed notification of the outbreak, limited staff and resources for control measures, abnormal weather conditions, and a serious gas pipeline explosion in the dengue hot spot areas in Kaohsiung City. However, the results of this surveillance indicated that both active and passive surveillance systems should be strengthened so appropriate public health measures can be taken promptly to prevent large-scale dengue outbreaks.
    Matched MeSH terms: Dengue Virus/genetics*; Viral Envelope Proteins/genetics; Genome, Viral/genetics
  7. Molecular evidence of Sarcocystis species in captive snakes in Japan
    Abe N, Matsubara K, Tamukai K, Miwa Y, Takami K
    Parasitol Res, 2015 Aug;114(8):3175-9.
    PMID: 26044884 DOI: 10.1007/s00436-015-4564-2
    Sarcocystis nesbitti, using snakes as the definitive host, is a causative agent of acute human muscular sarcocystosis in Malaysia. Therefore, it is important to explore the distribution and prevalence of S. nesbitti in snakes. Nevertheless, epizootiological information of S. nesbitti in snakes remains insufficient because few surveys have assessed Sarcocystis infection in snakes in endemic countries. In Japan, snakes are popular exotic pet animals that are imported from overseas, but the degree of Sarcocystis infection in them remains unclear. The possibility exists that muscular sarcocystosis by S. nesbitti occurs in contact with captive snakes in non-endemic countries. For a total of 125 snake faecal samples from 67 snake species collected at animal hospitals, pet shops and a zoo, this study investigated the presence of Sarcocystis using polymerase chain reaction (PCR) for the 18S ribosomal RNA gene (18S rDNA). Four (3.2%) faecal samples were positive by PCR. Phylogenetic analysis of the 18S rDNA sequences obtained from four amplification products revealed one isolate from a beauty snake (Elaphe taeniura), Sarcocystis zuoi, which uses rat snakes as the definitive host. The isolate from a Macklot's python (Liasis mackloti) was closely related with unidentified Sarcocystis sp. from reticulated pythons in Malaysia. The remaining two isolates from tree boas (Corallus spp.) were closely related with Sarcocystis lacertae, Sarcocystis gallotiae and unidentified Sarcocystis sp. from smooth snakes, Tenerife lizards and European shrews, respectively. This report is the first of a study examining the distribution of Sarcocystis species in captive snakes in Japan.
    Matched MeSH terms: DNA, Ribosomal/genetics; RNA, Ribosomal, 18S/genetics; Sarcocystis/genetics*
  8. Fulltext Non-invasive prenatal diagnosis using fetal DNA in maternal plasma: a preliminary study for identification of paternally-inherited alleles using single nucleotide polymorphisms
    Chen JJ, Tan JA, Chua KH, Tan PC, George E
    BMJ Open, 2015 Jul 22;5(7):e007648.
    PMID: 26201722 DOI: 10.1136/bmjopen-2015-007648
    OBJECTIVES: Single nucleotide polymorphism (SNP) with a mutation can be used to identify the presence of the paternally-inherited wild-type or mutant allele as result of the inheritance of either allele in the fetus and allows the prediction of the fetal genotype. This study aims to identify paternal SNPs located at the flanking regions upstream or downstream from the β-globin gene mutations at CD41/42 (HBB:c.127_130delCTTT), IVS1-5 (HBB:c.92+5G>C) and IVS2-654 (HBB:c.316-197C>T) using free-circulating fetal DNA.

    SETTING: Haematology Lab, Department of Biomedical Science, University of Malaya.

    PARTICIPANTS: Eight couples characterised as β-thalassaemia carriers where both partners posed the same β-globin gene mutations at CD41/42, IVS1-5 and IVS2-654, were recruited in this study.

    OUTCOME MEASURES: Genotyping was performed by allele specific-PCR and the locations of SNPs were identified after sequencing alignment.

    RESULTS: Genotype analysis revealed that at least one paternal SNP was present for each of the couples. Amplification on free-circulating DNA revealed that the paternal mutant allele of SNP was present in three fcDNA. Thus, the fetuses may be β-thalassaemia carriers or β-thalassaemia major. Paternal wild-type alleles of SNP were present in the remaining five fcDNA samples, thus indicating that the fetal genotypes would not be homozygous mutants.

    CONCLUSIONS: This preliminary research demonstrates that paternal allele of SNP can be used as a non-invasive prenatal diagnosis approach for at-risk couples to determine the β-thalassaemia status of the fetus.

    Matched MeSH terms: beta-Thalassemia/genetics; DNA, Intergenic/genetics*; beta-Globins/genetics*
  9. The evolutionary origins of Southeast Asian Ovalocytosis
    Paquette AM, Harahap A, Laosombat V, Patnode JM, Satyagraha A, Sudoyo H, et al.
    Infect Genet Evol, 2015 Aug;34:153-9.
    PMID: 26047685 DOI: 10.1016/j.meegid.2015.06.002
    Southeast Asian Ovalocytosis (SAO) is a common red blood cell disorder that is maintained as a balanced polymorphism in human populations. In individuals heterozygous for the SAO-causing mutation there are minimal detrimental effects and well-documented protection from severe malaria caused by Plasmodium vivax and Plasmodium falciparum; however, the SAO-causing mutation is fully lethal in utero when homozygous. The present-day high frequency of SAO in Island Southeast Asia indicates the trait is maintained by strong heterozygote advantage. Our study elucidates the evolutionary origin of SAO by characterizing DNA sequence variation in a 9.5 kilobase region surrounding the causal mutation in the SLC4A1 gene. We find substantial haplotype diversity among SAO chromosomes and estimate the age of the trait to be approximately 10,005 years (95% CI: 4930-23,200 years). This date is far older than any other human malaria-resistance trait examined previously in Southeast Asia, and considerably pre-dates the widespread adoption of agriculture associated with the spread of speakers of Austronesian languages some 4000 years ago. Using a genealogy-based method we find no evidence of historical positive selection acting on SAO (s=0.0, 95% CI: 0.0-0.03), in sharp contrast to the strong present-day selection coefficient (e.g., 0.09) estimated from the frequency of this recessively lethal trait. This discrepancy may be due to a recent increase in malaria-driven selection pressure following the spread of agriculture, with SAO targeted as a standing variant by positive selection in malarial populations.
    Matched MeSH terms: Anion Exchange Protein 1, Erythrocyte/genetics*; Elliptocytosis, Hereditary/genetics*; Malaria/genetics*
  10. Fulltext Differential Gene Expression Reflects Morphological Characteristics and Physiological Processes in Rice Immunity against Blast Pathogen Magnaporthe oryzae
    Azizi P, Rafii MY, Mahmood M, Abdullah SN, Hanafi MM, Nejat N, et al.
    PLoS One, 2015;10(5):e0126188.
    PMID: 26001124 DOI: 10.1371/journal.pone.0126188
    The rice blast fungus Magnaporthe oryzae is a serious pathogen that jeopardises the world's most important food-security crop. Ten common Malaysian rice varieties were examined for their morphological, physiological and genomic responses to this rice blast pathogen. qPCR quantification was used to assess the growth of the pathogen population in resistant and susceptible rice varieties. The chlorophyll content and photosynthesis were also measured to further understand the disruptive effects that M. oryzae has on infected plants of these varieties. Real-time PCR was used to explore the differential expression of eight blast resistance genes among the ten local varieties. Blast disease has destructive effects on the growth of rice, and the findings of our study provide evidence that the Pikh, Pi9, Pi21, and Osw45 genes are involved in defence responses in the leaves of Malaysian rice at 31 h after inoculation with M. oryzae pathotype P7.2. Both the chlorophyll content and photosynthesis were reduced, but the levels of Pikh gene expression remained constant in susceptible varieties, with a developed pathogen population and mild or severe symptoms. The Pi9, Pi21, and Osw45 genes, however, were simultaneously upregulated in infected rice plants. Therefore, the presence of the Pikh, Pi9, Pi21, and Osw45 genes in the germplasm is useful for improving the resistance of rice varieties.
    Matched MeSH terms: Oryza/genetics*; Host-Pathogen Interactions/genetics*; Disease Resistance/genetics*
  11. Fulltext Molecular characterization of two Malaysian patients with Wiskott-Aldrich syndrome
    Baharin MF, Kader Ibrahim SB, Yap SH, Abdul Manaf AM, Mat Ripen A, Dhaliwal JS
    Malays J Pathol, 2015 Aug;37(2):153-8.
    PMID: 26277674 MyJurnal
    The Wiskott-Aldrich Syndrome (WAS) is an X-linked immunodeficiency condition characterized by microthrombocytopenia, eczema and recurrent infections. It is caused by mutations in the Wiskott-Aldrich Syndrome protein (WASP) gene. We investigated two Malay boys who presented with congenital thrombocytopenia, eczema and recurrent infections. Here we report two cases of WASP mutation in Malaysia from two unrelated families. One had a novel missense mutation in exon 1 while the other had a nonsense mutation in exon 2. Both patients succumbed to diseaserelated complications. A differential diagnosis of WAS should be considered in any male child who present with early onset thrombocytopenia, especially when this is associated with eczema and recurrent infections.
    Matched MeSH terms: Wiskott-Aldrich Syndrome/genetics*; Asian Continental Ancestry Group/genetics*; Wiskott-Aldrich Syndrome Protein/genetics*
  12. Fulltext Biochemical Modulation of Lipid Pathway in Microalgae Dunaliella sp. for Biodiesel Production
    Talebi AF, Tohidfar M, Mousavi Derazmahalleh SM, Sulaiman A, Baharuddin AS, Tabatabaei M
    Biomed Res Int, 2015;2015:597198.
    PMID: 26146623 DOI: 10.1155/2015/597198
    Exploitation of renewable sources of energy such as algal biodiesel could turn energy supplies problem around. Studies on a locally isolated strain of Dunaliella sp. showed that the mean lipid content in cultures enriched by 200 mg L(-1) myoinositol was raised by around 33% (1.5 times higher than the control). Similarly, higher lipid productivity values were achieved in cultures treated by 100 and 200 mg L(-1) myoinositol. Fluorometry analyses (microplate fluorescence and flow cytometry) revealed increased oil accumulation in the Nile red-stained algal samples. Moreover, it was predicted that biodiesel produced from myoinositol-treated cells possessed improved oxidative stability, cetane number, and cloud point values. From the genomic point of view, real-time analyses revealed that myoinositol negatively influenced transcript abundance of AccD gene (one of the key genes involved in lipid production pathway) due to feedback inhibition and that its positive effect must have been exerted through other genes. The findings of the current research are not to interprete that myoinositol supplementation could answer all the challenges faced in microalgal biodiesel production but instead to show that "there is a there there" for biochemical modulation strategies, which we achieved, increased algal oil quantity and enhanced resultant biodiesel quality.
    Matched MeSH terms: Signal Transduction/genetics; Lipid Metabolism/genetics*; Microalgae/genetics
  13. Ingestion of food pellets containing Escherichia coli overexpressing the heat-shock protein DnaK protects Penaeus vannamei (Boone) against Vibrio harveyi (Baumann) infection
    Sinnasamy S, Noordin NM, MacRae TH, Bin Abdullah MI, Bossier P, Wahid ME, et al.
    J Fish Dis, 2016 May;39(5):577-84.
    PMID: 26132358 DOI: 10.1111/jfd.12390
    Feeding aquatic animals with bacterial encapsulated heat-shock proteins (Hsps) is potentially a new method to combat vibriosis, an important disease affecting aquatic animals used in aquaculture. Food pellets comprised of shrimp and containing Escherichia coli overexpressing either DnaK-DnaJ-GrpE, the prokaryotic equivalents of Hsp70-Hsp40-Hsp20, or only DnaK were fed to juveniles of the white leg shrimp Penaeus vannamei, and protection against pathogenic Vibrio harveyi was determined. Maintaining pellets at different temperatures for varying lengths of time reduced the number of live adhering E. coli, as did contact with sea water, demonstrating that storage and immersion adversely affected bacterial survival and attachment to pellets. Feeding P. vannamei with E. coli did not compromise their survival, indicating that the bacteria were not pathogenic to shrimp. Feeding P. vannamei with pellets containing bacteria overproducing DnaK (approximately 60 cells g(-1) pellets) boosted P. vannamei survival twofold against V. harveyi, suggesting that DnaK plays a role in Vibrio tolerance. Pellets containing DnaK were effective in providing protection to P. vannamei for up to 2 weeks before loss of viability and that DnaK encapsulated by these bacteria enhanced shrimp resistance against Vibrio infection.
    Matched MeSH terms: Bacterial Proteins/genetics*; Escherichia coli/genetics*; HSP70 Heat-Shock Proteins/genetics*
  14. The complex phylogeography of the Indo-Malayan Alophoixus bulbuls with the description of a putative new ring species complex
    Fuchs J, Ericson PG, Bonillo C, Couloux A, Pasquet E
    Mol Ecol, 2015 Nov;24(21):5460-74.
    PMID: 26224534 DOI: 10.1111/mec.13337
    The Indo-Malayan bioregion has provided some of the most spectacular discoveries of new vertebrate species (e.g. saola, khanyou, bare-faced bulbul) over the last 25 years. Yet, very little is known about the processes that led to the current biodiversity in this region. We reconstructed the phylogeographic history of a group of closely related passerines, the Alophoixus bulbuls. These birds are continuously distributed in Indo-Malaya around the Thailand lowlands such that their distribution resembles a ring. Our analyses revealed a single colonization event of the mainland from Sundaland with sequential divergence of taxa from southwest to northeast characterized by significant gene flow between parapatric taxa, and reduced or ancient gene flow involving the two taxa at the extremities of the ring. We detected evidence of population expansion in two subspecies, including one that was involved in the closing of the ring. Hence, our analyses indicate that the diversification pattern of Alophoixus bulbuls fits a ring species model driven by geographic isolation. To our knowledge, the Alophoixus bulbuls represent the first case of a putative broken ring species complex in Indo-Malaya. We also discuss the implications of our results on our understanding of the biogeography in Indo-Malaya.
    Matched MeSH terms: Cell Nucleus/genetics; DNA, Mitochondrial/genetics; Genetics, Population
  15. Fulltext Genetic variation of pfhrp2 in Plasmodium falciparum isolates from Yemen and the performance of HRP2-based malaria rapid diagnostic test
    Atroosh WM, Al-Mekhlafi HM, Al-Jasari A, Sady H, Al-Delaimy AK, Nasr NA, et al.
    Parasit Vectors, 2015;8:388.
    PMID: 26198252 DOI: 10.1186/s13071-015-1008-x
    The genetic variation in the Plasmodium falciparum histidine-rich protein 2 (pfhrp2) gene that may compromise the use of pfhrp2-based rapid diagnostic tests (RDTs) for the diagnosis of malaria was assessed in P. falciparum isolates from Yemen.
    Matched MeSH terms: Antigens, Protozoan/genetics*; Plasmodium falciparum/genetics; Protozoan Proteins/genetics*
  16. Fulltext Molecular characterisation of new organisation of plnEF and plw loci of bacteriocin genes harbour concomitantly in Lactobacillus plantarum I-UL4
    Tai HF, Foo HL, Abdul Rahim R, Loh TC, Abdullah MP, Yoshinobu K
    Microb Cell Fact, 2015;14:89.
    PMID: 26077560 DOI: 10.1186/s12934-015-0280-y
    Bacteriocin-producing Lactic acid bacteria (LAB) have vast applications in human and animal health, as well as in food industry. The structural, immunity, regulatory, export and modification genes are required for effective bacteriocin biosynthesis. Variations in gene sequence, composition and organisation will affect the antimicrobial spectrum of bacteriocin greatly. Lactobacillus plantarum I-UL4 is a novel multiple bacteriocin producer that harbours both plw and plnEF structural genes simultaneous which has not been reported elsewhere. Therefore, molecular characterisation of bacteriocin genes that harboured in L. plantarum I-UL4 was conducted in this study.
    Matched MeSH terms: Bacterial Proteins/genetics*; Bacteriocins/genetics; Lactobacillus plantarum/genetics*
  17. Fulltext TERT gene harbors multiple variants associated with pancreatic cancer susceptibility
    Campa D, Rizzato C, Stolzenberg-Solomon R, Pacetti P, Vodicka P, Cleary SP, et al.
    Int J Cancer, 2015 Nov 01;137(9):2175-83.
    PMID: 25940397 DOI: 10.1002/ijc.29590
    A small number of common susceptibility loci have been identified for pancreatic cancer, one of which is marked by rs401681 in the TERT-CLPTM1L gene region on chromosome 5p15.33. Because this region is characterized by low linkage disequilibrium, we sought to identify whether additional single nucleotide polymorphisms (SNPs) could be related to pancreatic cancer risk, independently of rs401681. We performed an in-depth analysis of genetic variability of the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC) genes, in 5,550 subjects with pancreatic cancer and 7,585 controls from the PANcreatic Disease ReseArch (PANDoRA) and the PanScan consortia. We identified a significant association between a variant in TERT and pancreatic cancer risk (rs2853677, odds ratio = 0.85; 95% confidence interval = 0.80-0.90, p = 8.3 × 10(-8)). Additional analysis adjusting rs2853677 for rs401681 indicated that the two SNPs are independently associated with pancreatic cancer risk, as suggested by the low linkage disequilibrium between them (r(2) = 0.07, D' = 0.28). Three additional SNPs in TERT reached statistical significance after correction for multiple testing: rs2736100 (p = 3.0 × 10(-5) ), rs4583925 (p = 4.0 × 10(-5) ) and rs2735948 (p = 5.0 × 10(-5) ). In conclusion, we confirmed that the TERT locus is associated with pancreatic cancer risk, possibly through several independent variants.
    Matched MeSH terms: Pancreatic Neoplasms/genetics*; Telomerase/genetics*; Carcinoma, Pancreatic Ductal/genetics*
  18. Molecular phylogeography of Angiostrongylus cantonensis (Nematoda: Angiostrongylidae) and genetic relationships with congeners using cytochrome b gene marker
    Yong HS, Eamsobhana P, Song SL, Prasartvit A, Lim PE
    Acta Trop, 2015 Aug;148:66-71.
    PMID: 25930187 DOI: 10.1016/j.actatropica.2015.04.020
    Angiostrongylus cantonensis is an important emerging zoonotic parasite causing human eosinophilic meningitis (or meningoencephalitis) in many parts of the world. To-date there is only a single study using mitochondrial cytochrome b (CYTB) gene to determine its genetic structure in eight geographical localities in Thailand. The present study examined the molecular phylogeography of this rat lungworm and its phylogenetic relationship with congeners using CYTB gene marker. A total of 15 CYTB haplotypes was found in 37 sequences from 14 geographical localities (covering north, west, east, central and south regions) in Thailand. These CYTB haplotypes were distinct from those of A. cantonensis for China and Hawaii. In Thailand, some CYTB haplotypes appeared to be confined to specific geographical localities. The partial CYTB DNA nucleotide sequences separated unequivocally the A. cantonensis isolates of Thailand, China and Hawaii as well as the congeners Angiostrongylus malaysiensis, A. costaricensis and Angiostrongylus vasorum, with A. malaysiensis grouped with A. cantonensis and A. costaricensis grouped with A. vasorum. Likewise the congeners of Metastrongylus and Onchocerca genera could also be clearly differentiated. The present study added two new definitive hosts (Bandicota savilei and Rattus losea) and three new localities (Mae Hong Son in the north, Tak in the west, and Phang Nga in the south) for A. malaysiensis in Thailand, indicating its wide occurrence in the country. Three CYTB haplotypes were found in the Thailand samples of A. malaysiensis. In addition to differentiation of congeners, CYTB gene marker could be used for determining the genetic diversity of a given population/taxon.
    Matched MeSH terms: Genetic Markers/genetics*; Angiostrongylus cantonensis/genetics*; Cytochromes b/genetics*
  19. Fulltext A common variant near TGFBR3 is associated with primary open angle glaucoma
    Li Z, Allingham RR, Nakano M, Jia L, Chen Y, Ikeda Y, et al.
    Hum Mol Genet, 2015 Jul 01;24(13):3880-92.
    PMID: 25861811 DOI: 10.1093/hmg/ddv128
    Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10(-33)), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.
    Matched MeSH terms: Glaucoma, Open-Angle/genetics*; Proteoglycans/genetics*; Receptors, Transforming Growth Factor beta/genetics*
  20. Evaluation of association studies and meta-analyses of MTHFR gene polymorphisms in colorectal cancer
    Haerian BS, Haerian MS
    Pharmacogenomics, 2015;16(4):413-25.
    PMID: 25823789 DOI: 10.2217/pgs.14.177
    There is a discrepancy between the results of 89 original studies and 15 meta-analyses investigating the association of MTHFR rs1801133 and rs1801131 polymorphisms with colorectal cancer (CRC) risk. We examined this hypothesis through meta-analyses of both loci and their diplotypes as well as evaluation of previous meta-analyses. The present meta-analysis showed that rs1801133 and rs1801131 might be CRC susceptibility variants in Americans and Australians and rs1801133 in Brazilians and Japanese. A strong linkage disequilibrium was observed between both loci and their diplotypes were associated with CRC risk. Evaluation of 15 meta-analyses showed a high discrepancy among their findings, mainly caused by population stratification of original studies and data analysis strategies in meta-analysis. Population stratification was more dominant in the studies from Australia, America and Brazil leading to false positive or negative results. In conclusion, these loci alone might modify the development of CRC in some ethnicities.
    Matched MeSH terms: Ethnic Groups/genetics; Colorectal Neoplasms/genetics*; Methylenetetrahydrofolate Reductase (NADPH2)/genetics*
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