The human cytochrome P450 (CYP) is a superfamily of enzymes that have been a focus in research for decades due to their prominent role in drug metabolism. CYP2C is one of the major subfamilies which ...metabolize more than 10% of all clinically used drugs. In the context of CYP2C19, several key genetic variations that alter the enzyme's activity have been identified and catalogued in the CYP allele nomenclature database. In this study, we investigated the presence of well-established variants as well as novel polymorphisms in the CYP2C19 gene of 62 Orang Asli from the Peninsular Malaysia. A total of 449 genetic variants were detected including 70 novel polymorphisms; 417 SNPs were located in introns, 23 in upstream, 7 in exons, and 2 in downstream regions. Five alleles and seven genotypes were inferred based on the polymorphisms that were found. Null alleles that were observed include CYP2C19*3 (6.5%), *2 (5.7%) and *35 (2.4%) whereas allele with increased function *17 was detected at a frequency of 4.8%. The normal metabolizer genotype was the most predominant (66.1%), followed by intermediate metabolizer (19.4%), rapid metabolizer (9.7%) and poor metabolizer (4.8%) genotypes. Findings from this study provide further insights into the CYP2C19 genetic profile of the Orang Asli as previously unreported variant alleles were detected through the use of massively parallel sequencing technology platform. The systematic and comprehensive analysis of CYP2C19 will allow uncharacterized variants that are present in the Orang Asli to be included in the genotyping panel in the future.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pigmentation is a readily scorable and quantitative human phenotype, making it an excellent model for studying multifactorial traits and diseases. Convergent human evolution from the ancestral state, ...darker skin, towards lighter skin colors involved divergent genetic mechanisms in people of European vs. East Asian ancestry. It is striking that the European mechanisms result in a 10-20-fold increase in skin cancer susceptibility while the East Asian mechanisms do not. Towards the mapping of genes that contribute to East Asian pigmentation there is need for one or more populations that are admixed for ancestral and East Asian ancestry, but with minimal European contribution. This requirement is fulfilled by the Senoi, one of three indigenous tribes of Peninsular Malaysia collectively known as the Orang Asli. The Senoi are thought to be an admixture of the Negrito, an ancestral dark-skinned population representing the second of three Orang Asli tribes, and regional Mongoloid populations of Indo-China such as the Proto-Malay, the third Orang Asli tribe. We have calculated skin reflectance-based melanin indices in 492 Orang Asli, which ranged from 28 (lightest) to 75 (darkest); both extremes were represented in the Senoi. Population averages were 56 for Negrito, 42 for Proto-Malay, and 46 for Senoi. The derived allele frequencies for SLC24A5 and SLC45A2 in the Senoi were 0.04 and 0.02, respectively, consistent with greater South Asian than European admixture. Females and individuals with the A111T mutation had significantly lighter skin (p = 0.001 and 0.0039, respectively). Individuals with these derived alleles were found across the spectrum of skin color, indicating an overriding effect of strong skin lightening alleles of East Asian origin. These results suggest that the Senoi are suitable for mapping East Asian skin color genes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We conducted a systematic characterization of CYP2C9 variants in 61 Orang Asli and 96 Singaporean Malays using the whole genome sequences data and compared the variants with the other 11 HapMap ...populations. The frequency of rs1057910 (CYP2C9*3) is the highest in the Orang Asli compared to other populations. Three alleles with clinical implication were detected in the Orang Asli while 2 were found in the Singaporean Malays. Large numbers of the Orang Asli are predicted to have reduced metabolic capacity and therefore they would require a lower dose of drugs which are metabolized by CYP2C9. They are also at increased risks of adverse effects and therapeutic failures. A large number of CYP2C9 variants in the Orang Asli were not in the Hardy Weinberg Equilibrium which could be due to small sample size or mutations that disrupt the equilibrium of allele frequencies. In conclusion, different polymorphism patterns, allele frequencies, genotype frequencies and LD blocks are observed between the Orang Asli, the Singaporean Malays and the other populations. The study provided new information on the genetic polymorphism of CYP2C9 which is important for the implementation of precision medicine for the Orang Asli.
Community development emphasizes the utilization of community resources, also known as community capitals. However, it is often difficult for the community to access these resources; this difficulty ...retards development. Such is the predicament faced by the Orang Kuala, for whom coastal changes have resulted in greater difficulty in accessing their community resources. Nor is that the only threat that they face. For affirmation of these threats, this article lists two objectives, that is, to identify the accessibility of marine resources and to explain the types of threats faced by the Orang Kuala. To achieve these objectives, a study was conducted involving 51 household heads and 5 Orang Kuala informants, all of whom are residents of Sungai Layau village in Johor, Malaysia. This study uses a mixed-method approach, the concurrent embedded design, and also interview-based questionnaires and in-depth interviews simultaneously. For the first objective, the results show that the Orang Kuala can still attain community resources in the form of marine products. However, the Orang Kuala faced three types of threats: trends, shocks, and seasonal changes. The most significant threat to the Orang Kuala is the trend, that is, cost of living and social problems. These threats can reduce their chances of acquiring benefits from these community resources. This condition is called “vulnerability of community capitals.” The objective of this article is to put forth proposals on how to increase the capacity of community resources for the Orang Kuala so that their community can attain sustainable development. This proposal is based on the reality that the threats facing the Orang Kuala are at a critical level and that they are ready to accept changes.
It is difficult to understand the changes in the community development process among Negritos in Malaysia without comprehensive data in a longitudinal framework. Thus, this study attempts to explain ...those changes through just such a study. The format adopts a quantitative approach to a survey designed for Negrito heads of households (HoH). The finding show a change happening in the community capitals, especially the human, social and cultural capitals. But other community capitals have not changed. Two main implications are highlighted: (1) the patterns of change among Negrito are revealed, community capitals under their control are changing, and (2) comprehensive data about the changes can only be obtained through a longitudinal panel study. Thus, longitudinal panel studies should be practiced by researchers in future, which is driving the need for massive and accurate data to develop a community.
Previously, any failure of Orang Asli development activity in Malaysia, was characterised by using a single term in all situations − "marginalisation". This generalisation was unfair to everyone ...involved in the Orang Asli development process, made it difficult to resolve problems, and resulted in tendencies to blame certain people. Based on ethnographic research in Kuala Gandah, Pahang, Malaysia, this article allocates three terms in the Orang Asli development marginalisation discourse: "secluded", "isolated", and "marginalised". "Secluded" refers to development activity that accidentally marginalises. "Isolated" refers to development activity that directly and deliberately marginalises. "Marginalised" refers to the Che Wong that were eliminating or avoiding development. These terms were exposed by weaknesses in the implementation of development, namely the role of a single dominant approach in development activities - the top-down approach - and a tendency to generalise the marginalisation of the Orang Asli. This article recommends that more care be taken to apply a development approach that deals with situations on a case-by-case basis and that utilises the partnership approach to development, involving all parties in all phases.
Traditional knowledge related to medicinal plants of the indigenous people is a valuable asset to the community and could potentially bring economic returns to them if it is utilized appropriately. ...While much of the existing researches have been focused on documenting the knowledge, not much however, has been made known on the ‘holistic’ practice of the knowledge at the community level particularly in the Malaysian context. This is an important aspect as documenting the knowledge alone would not bring any meaning if the knowledge itself is not sustainably practiced by the communities who hold the knowledge. However, it is not an easy task to understand the management aspect of the knowledge especially if the researcher comes from a ‘different world view’ that the indigenous people themselves. This study is an attempt to combine two methodologies namely ethnographic approach as data gathering method and the principles of grounded theory approach as data analysis in understanding how the traditional knowledge related to medicinal plants is being protected by the indigenous people. Using the Orang Asli Batek in Kuala Koh, Gua Musang, Kelantan as a case study, this research involved multiple prolonged stays with the community (2013-2016) and employed ethnographic techniques of individual and group interviews, observation and participant observation as well as document analysis to gather the data. The collected data was analysed using the principles of grounded theory where all responses that were recorded in verbatim was organised and analysed in stages of coding such as ‘initial coding’, ‘selective coding’ and ‘theme’ which upon further analysis, had enabled the description of the characteristics of the traditional knowledge related to medicinal plants of the Bateks. The result of this study found that the combination of the two methodologies are indeed useful and in fact are complementary with each other in understanding the characteristics of the traditional knowledge related to medicinal plants of the Bateks of Kuala Koh as part of the indigenous community in the country. In particular, employing the two methods has enabled the study to identify the characteristics (forms) of the TK that can be found in an indigenous community such as the Bateks of Kuala Koh. This research has provided a greater understanding on the existing state of protecting the TK being practiced by the Bateks. The study also provides useful contribution to the body of knowledge as the methodological approach used could be employed by future researches in understanding similar approach in understanding similar phenomena.
Traditional knowledge related to medicinal plants of the indigenous people are indeed a useful asset for the community. The knowledge that had been traditionally inherited from their ancestors is an ...integral part of their survival as they live symbiotically with the forests. While many researches and literatures are focusing on documenting and recording these knowledge, not much has been researched in understanding the holistic process of the knowledge management particularly at the indigenous community level. This paper provides an attempt to reveal empirical findings about the management and use of medicinal plants in ailment healing rituals. In order to enable a holistic view of the management of knowledge at the study site, the main question asked was what happened during the four processes of knowledge management namely knowledge generation, knowledge codification, knowledge utilization and knowledge transfer. Using the Batek community of Kuala Koh, Gua Musang, in the state of Kelantan as a case study, ethnographic methods of individual and group interviews, observations and participants observations as well as document analysis, were employed to gather the data from the study site and the grounded theory approach was used for data analysis to enable the emergence of the themes to understand the phenomena at the study site. The study, conducted from 2014-2016, involved prolonged stays with the community. The findings revealed that there was an ‘undocumented means of knowledge generation with potential loss of traditional knowledge’, while there was a non-codified knowledge being practiced in the community and widespread inability of basic reading and writing skills among younger generation. In addition, there was a high level of traditional knowledge utilisation in the community but some procedures such as ritual practices have been simplified while there was a complete absence of documentation of traditional knowledge by members of the community that might weaken knowledge transfer.
The role and importance of education and learning as an effective way to ensure a participatory approach in natural resource management and conservation has received considerable attention in recent ...years. On Langkawi Island, the formation of cooperative community resource management, Komuniti Pengurusan Sumber Perikanan (KPSP), or, formerly, fishermen economic groups, Kumpulan Ekonomi Nelayan (KEN), in 2001 is a significant attempt to emphasise the value of local involvement in natural resource management. This article aims to examine the importance of local community engagement in resource management through participation in selected fishing communities on the island. To this purpose, concepts from transformative learning theory are applied to understand how interactions among adults, through their participation in resource management, can promote learning and social change. The findings indicate a number of motivators and challenges to education, such as opportunities for dialogues, leadership and changes in behaviour, that occur at the community level. In conclusion, this study concurs that active local participation in resource management would allow members of the community to learn about natural resources and that such learning can lead to concrete actions on the ground towards sustainable solutions. Therefore, further research must focus on improving the forms of local participation in resource management to provide space for more and more effective education.