Allogeneic stem cell transplantation is a treatment option for malignant and non-malignant disorders in children. For children with no HLA-matched sibling or related stem cell donors, there is the option of unrelated cord blood donors. At the University of Malaya Medical Centre (UMMC) in Kuala Lumpur, the first unrelated cord blood transplantation (CBT) was performed in October 1997. All unrelated CBT performed in UMMC relied on cord blood units imported from overseas. DNA typing with variable number of tandem repeat (VNTR) loci was done to qualitatively evaluate engraftment in 15 unrelated CBT. In all the fifteen cases that were evaluated, molecular evidence of engraftment or non-engraftment correlated with the clinical findings.
Seventeen single nucleotide polymorphisms (SNPs) have been identified so far, within the beta-2 receptor (beta(2) AR) gene. The presence of so many SNPs within the beta(2) AR gene causes a problem, for those studying beta(2) AR pharmacogenetics, in relation to which SNPs to choose. Most of the work has focused on the three common SNPs within the coding block (alleles 16, 27 and 164) and the techniques developed have been for these three functionally important alleles.
Pristine tropical rainforests in Southeast Asia have rich species diversity and are important habitats for many plant species. However, the extent of these forests has declined in recent decades and they have become fragmented due to human activities. These developments may reduce the genetic diversity of species within them and, consequently, the species' ability to adapt to environmental changes. Our objective in the study presented here was to clarify the effect of tree density on the genetic diversity and gene flow patterns of Shorea leprosula Miq. populations in Peninsular Malaysia. For this purpose, we related genetic diversity and pollen flow parameters of seedling populations in study plots to the density of mature trees in their vicinity. The results show that gene diversity and allelic richness were not significantly correlated to the mature tree density. However, the number of rare alleles among the seedlings and the selfing rates of the mother trees were negatively correlated with the density of the adult trees. Furthermore, in a population with high mature tree density pollination distances were frequently <200 m, but in populations with low adult tree density the distances were longer. These findings suggest that the density of flowering trees affects selfing rates, gene flow and, thus, the genetic diversity of S. leprosula populations. We also found an individual S. leprosula tree with a unique reproductive system, probably apomictic, mating system.
Behavioural observations suggest that orang-utans are semi-solitary animals with females being philopatric and males roaming more widely in search of receptive partners, leading to the prediction that females are more closely related than males at any given site. In contrast, our study presents evidence for male and female philopatry in the orang-utan. We examined patterns of relatedness and parentage in a wild orang-utan population in Borneo using noninvasively collected DNA samples from animals observed to defecate, and microsatellite markers to assess dispersal and mating strategies. Surprisingly, resident females were equally as related to other resident females (mean r(xy) = 0.303) as resident males were to other resident males (mean r(xy) = 0.305). Moreover, resident females were more related to each other and to the resident males than they were to nonresident females, and resident males were more related to each other (and resident females) than they were to nonresident males. We assigned genetic mothers to 12 individuals in the population, while sires could be identified for eight. Both flanged males and unflanged males achieved paternity, similar to findings reported for Sumatran orang-utans.
Genetic divergence in geographically isolated populations is a prerequisite for allopatric speciation, one of the most common modes of speciation. In ecologically equivalent populations existing within a small, environmentally homogeneous area, an important role for environmentally neutral divergence is often found or inferred. We studied a species complex of conspicuously shaped Opisthostoma land snails on scattered limestone outcrops within a small area of lowland rainforest in Borneo. We used shell morphometrics, mitochondrial and nuclear DNA sequences, and marks of predation to study the factors involved in allopatric divergence. We found that a striking geographic divergence exists in shell morphology, which is partly associated with neutral genetic divergence. We also found geographic differentiation in the behavior of the snails' invertebrate predator and evidence of an evolutionary interaction between aspects of shell shape and predator behavior. Our study shows that adaptation to biotic aspects of the environment may play a more important role in allopatric speciation than previously suspected, even on a geographically very small scale.
A revision of the genus Leopoldamys is presented, and both the species composition and distribution in Indochina and Sundaic regions is reinvestigated. The phylogeny of the genus is recovered based on Cyt b, COI, and IRBP gene analyses. Five basal and 16 secondary monophyletic phylogenetic lineages were identified. A taxonomic reassessment of the continental and Sundaic populations is performed based on morphological verification of the genetically defined clades. Six clades were recovered in the phylogenetic analyses and correspond to morphologically defined species: L. revertens (distributed in lowlands of eastern and central Indochina), L. herberti (western and central Indochina, northward to northern Vietnam), L. edwardsi (China and northern Vietnam, northward of 21 degrees N), L. milleti (endemic of Dalat Plateau, southern Vietnam), L. sabanus (Borneo), and L. vociferans (lowlands of the Malacca Peninsula, northward to southwestern Thailand). The absence of proper L. sabanus in continental Indochina is revealed. The substitute name for the species known from the majority of Indochina under the name of L. sabanus should be L. revertens. The name L. neilli, which has been ascribed to populations from Thailand and Vietnam, is a junior synonym of L. herberti. Two related but rather divergent clades are found in Sumatra and the Malacca Peninsula. Based on their considerable genetic distances, these forms should be regarded as separate species from the L. sabanus type-bearing populations of Borneo, or as the members of L. sabanus polytypic superspecies. The substitute name for the lineage-bearing taxon from Malacca should be L. vociferans. The continental populations of Leopoldamys can be distinguished from each other by external and cranial characters and may be subdivided into four species. Two of these species (L. revertens and L. milleti) are well distinguished by external and cranial morphology, whereas the other two species (L. herberti and L. edwardsi) may be treated as sibling species that are difficult to distinguish based on morphological characters.
This revision completes a taxonomic survey of fireflies (Coleoptera: Lampyridae) in the area encompassed by Australia, the Republic of Palau, Federated States of Micronesia, Papua New Guinea, Indonesia (West Irian/Papua), Solomon Islands, New Caledonia, Vanuatu and Fiji. It finalises the taxonomic issues arising from the 1969–70 voyage of the scientific vessel Alpha Helix to New Guinea. The firefly fauna of this area is exclusively Luciolinae. The scope of the revision was extended to include all known Luciolinae genera and certain species from SE Asia, and a phylogenetic analysis of 436 morphological characters of males, females, and associated larvae includes 142 Luciolinae species (Ballantyne & Lambkin 2009, and Fu et al. 2012a). The phylogenetic analyses infer four major groups within the Luciolinae. The monotypic Missimia Ballantyne is sister to all remaining Luciolinae and forms a grade to Aquatica Fu etBallantyne. The large clade of Curtos Motschulsky, Photuroluciola Pic, Colophotia Motschulsky, Poluninius gen. nov., Pyrophanes Olivier, Pteroptyx s. str. Olivier, Medeopteryx gen. nov., Trisinuata gen. nov., and Australoluciola gen. nov.forms a grade to the clade of Luciola s. str. Laporte (including Bourgeoisia Olivier). The monotypic Emeia Fu et al.forms a grade with a clade of Luciola and Pygoluciola Wittmer, sister to a large clade of Convexa Ballantyne, Pacifica gen. nov., Magnalata Ballantyne, Lloydiella Ballantyne, Asymmetricata Ballantyne, Pygatyphella s. str. Ballantyne, Atyphella Olliff, Aquilonia Ballantyne, and Gilvainsula Ballantyne. Luciola is paraphyletic, found in up to six clades across the tree. Together with Luciola, Magnalata, Aquilonia, and Gilvainsula render Atyphella paraphyletic. The new genera described here are all monophyletic and supported in the phylogenetic analyses that also provide evidence for the inclusion of taxa within them. Twenty-three genera including five new ones, and ten new species, are recognised and keys are presented for the males and females. Certain females are characterised by the nature of their bursa plates. Australoluciola gen. nov. is proposed for ten species from Australia and New Guinea, seven transferred from Luciola and three new, with species keyed from males, all of which have an entire light organ in ventrite 7. Aus. anthracina (Olivier), Aus. aspera (Olivier), Aus. australis (F.), Aus. flavicollis (MacLeay), Aus. foveicollis (Olivier), Aus. nigra (Olivier) and Aus. orapallida (Ballantyne) are transferred from Luciola with males assigned to Aus. aspera(Olivier), and a lectotype designated for Luciola foveicollis Olivier; Aus. baduria sp. nov., Aus. fuscamagna sp. nov.,Aus. fuscaparva sp. nov., Aus. japenensis sp. nov. and Aus. pharusaurea sp. nov. are described. Females of Aus. australis and Aus. flavicollis have two pairs of wide bursa plates. The bent-winged fireflies of New Guinea and Australia are removed from Pteroptyx Olivier and assigned to Medeopteryx gen. nov. and Trisinuata gen. nov. Medeopteryx gen. nov. is erected for 17 species including two new; all have ventrite 7 with an entire light organ, trisinuate posterior margin and short posterolateral projections; the following 14 species in which males have deflexed elytral apices are transferred from Pteroptyx Olivier: M. amilae (Satô), M. antennata (Olivier), M. corusca (Ballantyne), M. cribellata (Olivier), M. effulgens (Ballantyne), M. elucens (Ballantyne), M. flagrans (Ballantyne), M. fulminea (Ballantyne), M. hanedai (Ballantyne), M. platygaster (Lea), M. similisantennata(Ballantyne), M. sublustris (Ballantyne), M. tarsalis (Olivier), and M. torricelliensis (Ballantyne). M. clipeata sp. nov. is described. Two species without deflexed elytral apices include M. pupilla (Olivier) which is transferred from Luciola, and M. similispupillae sp. nov. A Lectotype is designated for Luciola pupilla (Olivier). Females of M. corusca(Ballantyne), M. cribellata (Olivier), M. effulgens (Ballantyne), and M. similispupillae sp. nov. have two pairs of wide bursa plates. The second genus including species in which the males have deflexed elytral apices is Trisinuata gen. nov., where all males have light organ in ventrite 7 bipartite and posterolateral projections expanded; it is proposed for eight New Guinean species: T. microthorax (Olivier), T. minor (Ballantyne), T. papuae (McDermott) and T. similispapuae(Ballantyne) are transferred from Pteroptyx Olivier, T. papuana (Olivier) previously known only from a female, has males associated and is transferred from Luciola, and T. caudabifurca sp. nov., T. dimidiata sp. nov. and T. apicula sp. nov. are described. Females of T. similispapuae (Ballantyne) have two pairs of wide bursa plates. Luciola s. str. is defined by scoring the type species L. italica (L), Bourgeoisia Olivier and Lampyroidea (based on its type species syriaca Costa) both of which are submerged into Luciola; Luciola s. str is addressed here from four Pacific Island species: L. hypocrita Olivier, L. antipodum Bourgeois both transferred from Bourgeoisia; L. aquilaclarasp. nov. and L. oculofissa sp. nov. are described. L. oculofissa sp. nov. is the only Luciolinae male known to lack light organs. Females of L. italica and L. hypocrita lack bursa plates.Pacifica gen. nov. is proposed for five species from the Solomon Islands transferred from Pygatyphella(Ballantyne), and which the phylogenetic analysis shows to be distinctive viz. P. limbatifusca (Ballantyne), P. limbatipennis (Pic), P. plagiata (Blanchard), P. russellia (Ballantyne), and P. salomonis (Olivier). A monotypic genus Poluninius gen. nov. is proposed for Pol. selangoriensis sp. nov. from Selangor, Malaysia. The genera Colophotia, Pteroptyx, Pyrophanes, and Pygoluciola are treated in an abbreviated fashion with generic diagnoses, lists of, and keys to, species. Pteroptyx bearni Olivier and P. tener Olivier are characterised from type specimens and female bursae and P. similis Ballantyne is synonymised with P. bearni. Luciola semilimbata Olivier is transferred to Pyrophanes, and Luciola cowleyi Blackburn to Pygoluciola. The following species are treated as species incertae sedis: L. melancholica Olivier, L. ruficollis Guérin-Ménéville. The New Guinean records of Luciola tenuicornis Olivier, L. timida Olivier and Photinus cinctellus Motschulsky are suspect. Fifteen of the species treated here are recognised by flashing patterns. The functions of the terminal abdominal modifications, origins of the Australopacific firefly fauna, and use of female and larval characters in interpretations of relationships are considered.
Molecular and morphological analyses indicate that a new upland species of the Cyrtodactylus sworderi complex, C. tebuensis sp. nov. from Gunung Tebu, Terengganu, Malaysia is most closely related to C. sworderi and together they form the sister lineage to C. quadrivirgatus. Cyrtodactylus tebuensis sp. nov. is differentiated from all other species of Sundaland Cyrtodactylus on the basis of having the unique combination of large, conical, keeled body tubercles; tubercles present on top of head, occiput, nape, and limbs, and extending posteriorly beyond base of tail; 43-51 ventral scales; no transversely enlarged, median subcaudal scales; proximal, subdigital lamellae transversely expanded; 17-21 subdigital lamellae on fourth toe; an abrupt transition between posterior and ventral femoral scales; enlarged femoral scales; no femoral or precloacal pores; no precloacal groove; body bearing four wide, bold, dark brown stripes (lateral stripe on each flank and a pair of paravertebral stripes); and a pairwise sequence divergence of 13.0% from its closest relative C. sworderi based on the mitochondrial gene ND2. Cyrtodactylus tebuensis sp. nov. is the first endemic upland species of gekkonid from northeastern Peninsular Malaysia and underscores the necessity for additional field work in all upland systems.
Complete deletions in the AZF (a, b, and c) sub-regions of the Y-chromosome have been shown to contribute to unexplained male infertility. However, the role of partial AZFc deletions in male infertility remains to be verified. Three types of partial AZFc deletions have been identified. They are gr/gr, b1/b3, and b2/b3 deletions. A recent meta-analysis showed that ethnic and geographical factors might contribute to the association of partial AZFc deletions with male infertility. This study analyzed the association of partial AZFc deletions in Malaysian infertile males. Fifty two oligozoospermic infertile males and 63 fertile controls were recruited to this study. Screening for partial AZFc deletions was done using the two sequence-tagged sites approach (SY1291 and SY1191) which were analyzed using both the conventional PCR gel-electrophoresis and the high resolution melt, HRM method. Gr/gr deletions were found in 11.53% of the cases and 9.52% of the controls (p = 0.725). A B2/b3 deletion was found in one of the cases (p = 0.269). No B1/b3 deletions were identified in this study. The results of HRM analysis were consistent with those obtained using the conventional PCR gel-electrophoresis method. The HRM analysis was highly repeatable (95% limit of agreement was -0.0879 to 0.0871 for SY1191 melting temperature readings). In conclusion, our study showed that partial AZFc deletions were not associated with male infertility in Malaysian subjects. HRM analysis was a reliable, repeatable, fast, cost-effective, and semi-automated method which can be used for screening of partial AZFc deletions.
Interindividual variability in drug response and the emergence of adverse drug effects are the main causes of treatment failure in cancer therapy. Functional membrane drug transporters play important roles in altering pharmacokinetic profile, resistance to treatment, toxicity and patient survival. Pharmacogenetic studies of these transporters are expected to provide new approaches for optimizing therapy. Taxanes are approved for the treatment of various cancers. Circulating taxanes are taken up by SLCO1B3 into hepatocytes. The CYP450 enzymes CYP3A4, CYP3A5 and CYP2C8 are responsible for the conversion of taxanes into their metabolites. Ultimately, ABCB1 and ABCC2 will dispose the metabolites into bile canaliculi. Polymorphisms of genes encoding for proteins involved in the transport and clearance of taxanes reduce excretion of the drugs, leading to development of toxicity in patients. This review addresses current knowledge on genetic variations of transporters affecting taxanes pharmacokinetics and toxicity, and provides insights into future direction for personalized medicine.
Mosquito-borne Chikungunya virus (CHIKV) has recently re-emerged globally. The epidemic East/Central/South African (ECSA) strains have spread for the first time to Asia, which previously only had endemic Asian strains. In Malaysia, the ECSA strain caused an extensive nationwide outbreak in 2008, while the Asian strains only caused limited outbreaks prior to this. To gain insight into these observed epidemiological differences, we compared genotypic and phenotypic characteristics of CHIKV of Asian and ECSA genotypes isolated in Malaysia.
The direction that a snail (Mollusca: Gastropoda) coils, whether dextral (right-handed) or sinistral (left-handed), originates in early development but is most easily observed in the shell form of the adult. Here, we review recent progress in understanding snail chirality from genetic, developmental and ecological perspectives. In the few species that have been characterized, chirality is determined by a single genetic locus with delayed inheritance, which means that the genotype is expressed in the mother's offspring. Although research lags behind the studies of asymmetry in the mouse and nematode, attempts to isolate the loci involved in snail chirality have begun, with the final aim of understanding how the axis of left-right asymmetry is established. In nature, most snail taxa (>90%) are dextral, but sinistrality is known from mutant individuals, populations within dextral species, entirely sinistral species, genera and even families. Ordinarily, it is expected that strong frequency-dependent selection should act against the establishment of new chiral types because the chiral minority have difficulty finding a suitable mating partner (their genitalia are on the 'wrong' side). Mixed populations should therefore not persist. Intriguingly, however, a very few land snail species, notably the subgenus Amphidromus sensu stricto, not only appear to mate randomly between different chiral types, but also have a stable, within-population chiral dimorphism, which suggests the involvement of a balancing factor. At the other end of the spectrum, in many species, different chiral types are unable to mate and so could be reproductively isolated from one another. However, while empirical data, models and simulations have indicated that chiral reversal must sometimes occur, it is rarely likely to lead to so-called 'single-gene' speciation. Nevertheless, chiral reversal could still be a contributing factor to speciation (or to divergence after speciation) when reproductive character displacement is involved. Understanding the establishment of chirality, the preponderance of dextral species and the rare instances of stable dimorphism is an important target for future research. Since the genetics of chirality have been studied in only a few pulmonate species, we also urge that more taxa, especially those from the sea, should be investigated.
Tree snails of the subgenus Amphidromus s. str. are unusual because of the chiral dimorphism that exists in many species, with clockwise (dextrally) and counter-clockwise (sinistrally) coiled individuals co-occurring in the same population. Given that mating in snails is normally impeded when the two partners have opposite coil, positive frequency-dependent selection should prevent such dimorphism from persisting. We test the hypothesis that a strong population structure with little movement between tree-based demes may result in the fixation of coiling morphs at a very small spatial scale, but apparent dimorphism at all larger scales. To do so, we describe the spatial structure in a Malaysian population of A. inversus (Müller, 1774) with 36% dextrals. We marked almost 700 juvenile and adult snails in a piece of forest consisting of 92 separate trees, and recorded dispersal and the proportions of dextrals and sinistrals in all trees over a 7-day period. We observed frequent movement between trees (155 events), and found that no trees had snail populations with proportions of dextrals and sinistrals that were significantly different from random. Upon recapture 1 year later, almost two-thirds of the snails had moved away from their original tree. We conclude that population structure alone cannot stabilise the coil dimorphism in Amphidromus.
Giant grouper (Epinephelus lanceolatus) is a commercially important species, but its wild population has recently been classified as vulnerable. This species has significant potential for use in aquaculture, though a greater understanding of population genetics is necessary for selective breeding programs to minimize kinship for genetically healthy individuals. High-throughput pyrosequencing of genomic DNA was used to identify and characterize novel tetra- and trinucleotide microsatellite markers in giant grouper from Sabah, Malaysia. In total, of 62,763 sequences containing simple sequence repeats (SSRs) were obtained, and 78 SSR loci were selected to possibly contain tetra- and trinucleotide repeats. Of these loci, 16 had tetra- and 8 had trinucleotide repeats, all of which exhibited polymorphisms within easily genotyped regions. A total of 143 alleles were identified with an average of 5.94 alleles per locus, with mean observed and expected heterozygosities of 0.648 and 0.620, respectively. Among of them, 15 microsatellite markers were identified without null alleles and with Hardy-Weinberg equilibrium. These alleles showed a combined non-exclusion probability of 0.01138. The probability of individual identification (PID) value combined with in descending order 12 microsatellite markers was 0.00008, which strongly suggests that the use of the microsatellite markers developed in this study in various combinations would result in a high resolution method for parentage analysis and individual identification. These markers could be used to establish a broodstock management program for giant grouper and to provide a foundation for genetic studies such as population structure, parentage analysis, and kinship selection.
Genetic variability and differences in wild striped snakehead Channa striata from Malaysia were analysed by genotyping nine novel nuclear microsatellite loci. Analysis revealed moderate-to-high genetic diversity in most of the populations, indicative of large effective population sizes. The highly diversified populations are admixed populations and, therefore, can be recommended as potential candidates for selective breeding and conservation since they each contain most of the alleles found in their particular region. Three homogenous groups of the wild populations were identified, apparently separated by effective barriers, in accordance with contemporary drainage patterns. The highest population pairwise FST found between members of the same group reflects the ancient population connectivity; yet prolonged geographical isolation resulted in adaptation of alleles to local contemporary environmental change. A significant relationship between genetic distance and geographical isolation was observed (r = 0·644, P < 0·01). Anthropogenic perturbations indicated apparent genetic proximity between distant populations.
In this study, we isolated two indigenous hydrocarbon-degrading bacteria from tarball found in Rhu Sepuluh beach, Terengganu, Malaysia. These bacteria were identified based on their physiological characteristic and 16S rRNA gene sequence analysis, and they showed 99% similarity with Cellulosimicrobium cellulans DSM 43879 and Acinetobacter baumannii ATCC 19606 respectively. Their hydrocarbon-degrading capabilities were tested using diesel-oil as sole carbon source. Results analysed using GC-MS, showed diesel-oil alkanes were degraded an average 64.4% by C. cellulans and 58.1% by A. baumannii with medium optical density reaching 0.967 (C. cellulans) and 1.515 (A. baumannii) in minimal salt media at 32°C for 10days. Individual diesel-oil alkanes were degraded between 10%-95.4% by C. cellulans and 0.2%-95.9% by A. baumannii. Both strains utilized diesel-oil for growth. The study suggests both strains are part of indigenous hydrocarbon-degrading bacteria in tarball with potential for bioremediation of oil-polluted marine environment.
DNA methylation, a major regulator of epigenetic modifications has been shown to alter the expression of genes that are involved in aspects of glucose metabolism such as glucose intolerance, insulin resistance, β-cell dysfunction and other conditions, and it ultimately leads to the pathogenesis of type 2 diabetes mellitus (T2DM). Current evidences indicate an association of DNA methylation with T2DM. This review provides an overview of how various factors play crucial roles in T2DM pathogenesis and how DNA methylation interacts with these factors. Additionally, an update on current techniques of DNA methylation analysis with their pros and cons is provided as a basis for the adoption of suitable techniques in future DNA methylation research towards better management of T2DM. To elucidate the mechanistic relationship between vital environmental factors and the development of T2DM, a better understanding of the changes in gene expression associated with DNA methylation at the molecular level is still needed.
Matched MeSH terms: Diabetes Mellitus, Type 2/genetics*