Displaying publications 1 - 20 of 53 in total

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  1. Fulltext Whole genome sequencing of amplified Plasmodium knowlesi DNA from unprocessed blood reveals genetic exchange events between Malaysian Peninsular and Borneo subpopulations
    Benavente ED, Gomes AR, De Silva JR, Grigg M, Walker H, Barber BE, et al.
    Sci Rep, 2019 07 08;9(1):9873.
    PMID: 31285495 DOI: 10.1038/s41598-019-46398-z
    The zoonotic Plasmodium knowlesi parasite is the most common cause of human malaria in Malaysia. Genetic analysis has shown that the parasites are divided into three subpopulations according to their geographic origin (Peninsular or Borneo) and, in Borneo, their macaque host (Macaca fascicularis or M. nemestrina). Whilst evidence suggests that genetic exchange events have occurred between the two Borneo subpopulations, the picture is unclear in less studied Peninsular strains. One difficulty is that P. knowlesi infected individuals tend to present with low parasitaemia leading to samples with insufficient DNA for whole genome sequencing. Here, using a parasite selective whole genome amplification approach on unprocessed blood samples, we were able to analyse recent genomes sourced from both Peninsular Malaysia and Borneo. The analysis provides evidence that recombination events are present in the Peninsular Malaysia parasite subpopulation, which have acquired fragments of the M. nemestrina associated subpopulation genotype, including the DBPβ and NBPXa erythrocyte invasion genes. The NBPXb invasion gene has also been exchanged within the macaque host-associated subpopulations of Malaysian Borneo. Our work provides strong evidence that exchange events are far more ubiquitous than expected and should be taken into consideration when studying the highly complex P. knowlesi population structure.
    Matched MeSH terms: Haplotypes/genetics
  2. The promoter region of the MDR1 gene is largely invariant, but different single nucleotide polymorphism haplotypes affect MDR1 promoter activity differently in different cell lines
    Wang B, Ngoi S, Wang J, Chong SS, Lee CG
    Mol. Pharmacol., 2006 Jul;70(1):267-76.
    PMID: 16608921
    The MDR1 multidrug transporter represents one of the better characterized drug transporters that play an important role in protecting the body against xenobiotic insults. Single nucleotide polymorphisms (SNPs) and SNP haplotypes within this gene have been variously associated with differences in MDR1 expression/function, drug response as well as disease susceptibility. Nonetheless, the effect of polymorphisms at the MDR1 promoter region on its promoter activity remains less characterized. Through the examination of approximately 1.5 kilobases of MDR1 promoter region from five populations, including the Chinese, Malays, Indians, European Americans, and African Americans, we identified eight low-frequency SNPs, of which only two were polymorphic in at least four of the five populations examined. The other SNPs are mainly population-specific, the majority of which occur only in the African-American population. Recapitulation of the various combinations of SNP haplotypes in vitro in promoter-reporter assays revealed a few notable trends. The African and European American-specific haplotypes tended to result in enhanced MDR1 promoter activity only in the human embryonic kidney (HEK) 293 cell line. Haplotype GCTAACC, which occurs at variable frequencies in all the populations examined, with Asians having much lower frequencies (<2%) compared with the European Americans/African Americans (>4%), affected MDR1 promoter activity differently in different cell lines. Compared with the commonest haplotype, GCTA-ACC haplotype resulted in a significant decrease in MDR1 promoter activity in HeLa cells (P < 0.05) but a significant increase in the same promoter activity in HEK293 cells (P < 0.05). These results suggest that the MDR1 promoter region is largely invariant but that different haplotypes have differential effects on the MDR1 promoter activity in different cell lines.
    Matched MeSH terms: Haplotypes/genetics*
  3. The pattern of HLA-A, -B and -DRB1 alleles and haplotypes of four Malay sub-ethnic groups namely Kelantan, Champa, Patani and Mandailing Malays of Peninsular Malaysia
    Allia S, Norazmi MN, Panneerchelvam S, Zafarina Z
    Hum Immunol, 2019 Jul;80(7):423-424.
    PMID: 30836128 DOI: 10.1016/j.humimm.2019.02.015
    "Bumiputra" or "son of the soil" is a term used to represent the Malays and other indigenous populations of Malaysia. The Malays are Austronesian speaking population and originated from different parts of the Indo-Malay Archipelago. The migration of Malay population from different parts of Indo-Malay Archipelago were mainly due to trading purposes which shaped the current Malay sub-ethnic groups with unique culture and with distinctive dialects. In this study, HLA typing was carried out using Sequence-based Typing (SBT) method on 109 individuals comprising of four Malay sub-ethnic groups namely Kelantan (n = 28), Champa (n = 29), Patani (n = 25) and Mandailing (n = 27) Malays. The HLA data is available in the Allele Frequencies Net Database (AFND).
    Matched MeSH terms: Haplotypes/genetics*
  4. Fulltext The genetic architecture of the MHC class II region in British Texel sheep
    Ali AO, Stear A, Fairlie-Clarke K, Brujeni GN, Isa NM, Salisi MS, et al.
    Immunogenetics, 2017 03;69(3):157-163.
    PMID: 27921144 DOI: 10.1007/s00251-016-0962-6
    Understanding the structure of the major histocompatibility complex, especially the number and frequency of alleles, loci and haplotypes, is crucial for efficient investigation of the way in which the MHC influences susceptibility to disease. Nematode infection is one of the most important diseases suffered by sheep, and the class II region has been repeatedly associated with differences in susceptibility and resistance to infection. Texel sheep are widely used in many different countries and are relatively resistant to infection. This study determined the number and frequency of MHC class II genes in a small flock of Texel sheep. There were 18 alleles at DRB1, 9 alleles at DQA1, 13 alleles at DQB1, 8 alleles at DQA2 and 16 alleles at DQB2. Several haplotypes had no detectable gene products at DQA1, DQB1 or DQB2, and these were defined as null alleles. Despite the large numbers of alleles, there were only 21 distinct haplotypes in the population. The relatively small number of observed haplotypes will simplify finding disease associations because common haplotypes provide more statistical power but complicate the discrimination of causative mutations from linked marker loci.
    Matched MeSH terms: Haplotypes/genetics*
  5. The Fabry disease-causing mutation, GLA IVS4+919G>A, originated in Mainland China more than 800 years ago
    Liang KH, Lu YH, Niu CW, Chang SK, Chen YR, Cheng CY, et al.
    J Hum Genet, 2020 Jul;65(7):619-625.
    PMID: 32246049 DOI: 10.1038/s10038-020-0745-7
    The Fabry disease-causing mutation, the GLA IVS4+919G>A (designated GLA IVS4), is very prevalent in patients with hypertrophic cardiomyopathy in Taiwan. This X-linked mutation has also been found in patients in Kyushu, Japan and Southeast Asia. To investigate the age and the possible ancestral origin of this mutation, a total of 33 male patients with the GLA IVS4+919G>A mutation, born in Taiwan, Japan, Singapore, Malaysia, Vietnam, and the Fujian and Guangdong provinces of China, were studied. Peripheral bloods were collected, and the Ilumina Infinium CoreExome-24 microarray was used for dense genotyping. A mutation-carrying haplotype was discovered which was shared by all 33 patients. This haplotype does not exist in 15 healthy persons without the mutation. Rather, a wide diversity of haplotypes was found in the vicinity of the mutation site, supporting the existence of a single founder of the GLA IVS4 mutation. The age of the founder mutation was estimated by the lengths of the mutation-carrying haplotypes based on the linkage-disequilibrium decay theory. The first, second, and third quartile of the age estimates are 800.7, 922.6, and 1068.4 years, respectively. We concluded that the GLA IVS4+919G>A mutation originated from a single mutational event that occurred in a Chinese chromosome more than 800 years ago.
    Matched MeSH terms: Haplotypes/genetics
  6. Fulltext Susceptibility and gene interaction study of the angiotensin II type 1 receptor (AGTR1) gene polymorphisms with non-alcoholic fatty liver disease in a multi-ethnic population
    Zain SM, Mohamed Z, Mahadeva S, Rampal S, Basu RC, Cheah PL, et al.
    PLoS One, 2013;8(3):e58538.
    PMID: 23484035 DOI: 10.1371/journal.pone.0058538
    Angiotensin II type 1 receptor (AGTR1) has been reported to play a fibrogenic role in non-alcoholic fatty liver disease (NAFLD). In this study, five variants of the AGTR1 gene (rs3772622, rs3772627, rs3772630, rs3772633, and rs2276736) were examined for their association with susceptibility to NAFLD. Subjects made up of 144 biopsy-proven NAFLD patients and 198 controls were genotyped using TaqMan assays. The liver biopsy specimens were histologically graded and scored according to the method of Brunt. Single locus analysis in pooled subjects revealed no association between each of the five variants with susceptibility to NAFLD. In the Indian ethnic group, the rs2276736, rs3772630 and rs3772627 appear to be protective against NAFLD (p = 0.010, p = 0.016 and p = 0.026, respectively). Haplotype ACGCA is shown to be protective against NAFLD for the Indian ethnic subgroup (p = 0.03). Gene-gene interaction between the AGTR1 gene and the patatin-like phospholipase domain-containing 3 (PNPLA3) gene, which we previously reported as associated with NAFLD in this sample, showed a strong interaction between AGTR1 (rs3772627), AGTRI (rs3772630) and PNPLA3 (rs738409) polymorphisms on NAFLD susceptibility (p = 0.007). Further analysis of the NAFLD patients revealed that the G allele of the AGTR1 rs3772622 is associated with increased fibrosis score (p = 0.003). This is the first study that replicates an association between AGTR1 polymorphism and NAFLD, with further details in histological features of NAFLD. There is lack of evidence to suggest an association between any of the five variants of the AGTR1 gene and NAFLD in the Malays and Chinese. In the Indians, the rs2276736, rs3772630 and rs3772627 appear to protect against NAFLD. We report novel findings of an association between the G allele of the rs3772622 with occurrence of fibrosis and of the gene-gene interaction between AGTR1gene and the much-studied PNPLA3 gene.
    Matched MeSH terms: Haplotypes/genetics
  7. Fulltext Singapore Genome Variation Project: a haplotype map of three Southeast Asian populations
    Teo YY, Sim X, Ong RT, Tan AK, Chen J, Tantoso E, et al.
    Genome Res, 2009 Nov;19(11):2154-62.
    PMID: 19700652 DOI: 10.1101/gr.095000.109
    The Singapore Genome Variation Project (SGVP) provides a publicly available resource of 1.6 million single nucleotide polymorphisms (SNPs) genotyped in 268 individuals from the Chinese, Malay, and Indian population groups in Southeast Asia. This online database catalogs information and summaries on genotype and phased haplotype data, including allele frequencies, assessment of linkage disequilibrium (LD), and recombination rates in a format similar to the International HapMap Project. Here, we introduce this resource and describe the analysis of human genomic variation upon agglomerating data from the HapMap and the Human Genome Diversity Project, providing useful insights into the population structure of the three major population groups in Asia. In addition, this resource also surveyed across the genome for variation in regional patterns of LD between the HapMap and SGVP populations, and for signatures of positive natural selection using two well-established metrics: iHS and XP-EHH. The raw and processed genetic data, together with all population genetic summaries, are publicly available for download and browsing through a web browser modeled with the Generic Genome Browser.
    Matched MeSH terms: Haplotypes/genetics*
  8. Fulltext Selected neuropeptide genes show genetic differentiation between Africans and non-Africans
    Tai KY, Wong K, Aghakhanian F, Parhar IS, Dhaliwal J, Ayub Q
    BMC Genet, 2020 03 14;21(1):31.
    PMID: 32171244 DOI: 10.1186/s12863-020-0835-8
    BACKGROUND: Publicly available genome data provides valuable information on the genetic variation patterns across different modern human populations. Neuropeptide genes are crucial to the nervous, immune, endocrine system, and physiological homeostasis as they play an essential role in communicating information in neuronal functions. It remains unclear how evolutionary forces, such as natural selection and random genetic drift, have affected neuropeptide genes among human populations. To date, there are over 100 known human neuropeptides from the over 1000 predicted peptides encoded in the genome. The purpose of this study is to analyze and explore the genetic variation in continental human populations across all known neuropeptide genes by examining highly differentiated SNPs between African and non-African populations.

    RESULTS: We identified a total of 644,225 SNPs in 131 neuropeptide genes in 6 worldwide population groups from a public database. Of these, 5163 SNPs that had ΔDAF |(African - non-African)| ≥ 0.20 were identified and fully annotated. A total of 20 outlier SNPs that included 19 missense SNPs with a moderate impact and one stop lost SNP with high impact, were identified in 16 neuropeptide genes. Our results indicate that an overall strong population differentiation was observed in the non-African populations that had a higher derived allele frequency for 15/20 of those SNPs. Highly differentiated SNPs in four genes were particularly striking: NPPA (rs5065) with high impact stop lost variant; CHGB (rs6085324, rs236150, rs236152, rs742710 and rs742711) with multiple moderate impact missense variants; IGF2 (rs10770125) and INS (rs3842753) with moderate impact missense variants that are in linkage disequilibrium. Phenotype and disease associations of these differentiated SNPs indicated their association with hypertension and diabetes and highlighted the pleiotropic effects of these neuropeptides and their role in maintaining physiological homeostasis in humans.

    CONCLUSIONS: We compiled a list of 131 human neuropeptide genes from multiple databases and literature survey. We detect significant population differentiation in the derived allele frequencies of variants in several neuropeptide genes in African and non-African populations. The results highlights SNPs in these genes that may also contribute to population disparities in prevalence of diseases such as hypertension and diabetes.

    Matched MeSH terms: Haplotypes/genetics
  9. Relationship between immunoglobulin allotypes and susceptibility to nasopharyngeal carcinoma in Malaysia
    Tarone RE, Levine PH, Yadav M, Pandey JP
    Cancer Res, 1990 Jun 1;50(11):3186-8.
    PMID: 1692255
    The relationship between immunoglobulin allotypes and risk of developing nasopharyngeal carcinoma was examined in a comparative study of 50 Chinese cases and 140 Chinese controls and 50 Malay cases and 79 Malay controls residing in Malaysia. Although the most common Gm phenotype was elevated in both Chinese and Malay nasopharyngeal carcinoma patients compared to their controls, there were no significant differences between cases and controls in the distribution of Gm haplotypes in either population. There were no differences between cases and controls in the distribution of Km alleles in either population. Thus a previously reported association of Km(1) with increased nasopharyngeal carcinoma risk in Tunisia is not confirmed in two Mongoloid populations in Malaysia.
    Matched MeSH terms: Haplotypes/genetics*
  10. Fulltext Positive selection in Europeans and East-Asians at the ABCA12 gene
    Sirica R, Buonaiuto M, Petrella V, Sticco L, Tramontano D, Antonini D, et al.
    Sci Rep, 2019 03 19;9(1):4843.
    PMID: 30890716 DOI: 10.1038/s41598-019-40360-9
    Natural selection acts on genetic variants by increasing the frequency of alleles responsible for a cellular function that is favorable in a certain environment. In a previous genome-wide scan for positive selection in contemporary humans, we identified a signal of positive selection in European and Asians at the genetic variant rs10180970. The variant is located in the second intron of the ABCA12 gene, which is implicated in the lipid barrier formation and down-regulated by UVB radiation. We studied the signal of selection in the genomic region surrounding rs10180970 in a larger dataset that includes DNA sequences from ancient samples. We also investigated the functional consequences of gene expression of the alleles of rs10180970 and another genetic variant in its proximity in healthy volunteers exposed to similar UV radiation. We confirmed the selection signal and refine its location that extends over 35 kb and includes the first intron, the first two exons and the transcription starting site of ABCA12. We found no obvious effect of rs10180970 alleles on ABCA12 gene expression. We reconstructed the trajectory of the T allele over the last 80,000 years to discover that it was specific to H. sapiens and present in non-Africans 45,000 years ago.
    Matched MeSH terms: Haplotypes/genetics
  11. Fulltext Positive selection footprints and haplotype distribution in the genome of dromedary camels
    Bahbahani H, Alfoudari A, Al-Ateeqi A, Al Abri M, Almathen F
    Animal, 2024 Mar;18(3):101098.
    PMID: 38377812 DOI: 10.1016/j.animal.2024.101098
    Dromedary camels are a domestic species characterized by various adaptive traits. Limited efforts have been employed toward identifying genetic regions and haplotypes under selection that might be related to such adaptations. These genetic elements are considered valuable sources that should be conserved to maintain the dromedaries' adaptability. Here, we have analyzed whole genome sequences of 40 dromedary camels from different Arabian Peninsula populations to assess their genetic relationship and define regions with signatures of selection. Genetic distinction based on geography was observed, classifying the populations into four groups: (1) North and Central, (2) West, (3) Southwest, and (4) Southeast, with substantial levels of genetic admixture. Using the de-correlated composite of multiple signal approach, which combines four intra-population analyses (Tajima's D index, nucleotide diversity, integrated haplotype score, and number of segregating sites by length), a total of 36 candidate regions harboring 87 genes were identified to be under positive selection. These regions overlapped with 185 haplotype blocks encompassing 1 340 haplotypes, of which 30 (∼2%) were found to be approaching fixation. The defined candidate genes are associated with different biological processes related to the dromedaries' adaptive physiologies, including neurological pathways, musculoskeletal development, fertility, fat distribution, immunity, visual development, and kidney physiology. The results of this study highlight opportunities for further investigations at the whole-genome level to enhance our understanding of the evolutionary pressures shaping the dromedary genome.
    Matched MeSH terms: Haplotypes/genetics
  12. Population structure and intraspecific aggression in the invasive ant species Anoplolepis gracilipes in Malaysian Borneo
    Drescher J, Blüthgen N, Feldhaar H
    Mol Ecol, 2007 Apr;16(7):1453-65.
    PMID: 17391269
    Invasive species are one of the main sources of the ongoing global loss of biodiversity. Invasive ants are known as particularly damaging invaders and their introductions are often accompanied by population-level behavioural and genetic changes that may contribute to their success. Anoplolepis gracilipes is an invasive ant that has just recently received increased attention due to its negative impact on native ecosystems. We examined the behaviour and population structure of A. gracilipes in Sabah, Malaysia. A total of 475 individuals from 24 colonies were genotyped with eight microsatellite markers. Intracolonial relatedness was high, ranging from 0.37 to 1 (mean +/- SD: 0.82 +/- 0.04), while intercolonial relatedness was low (0.0 +/- 0.02, range -0.5-0.76). We compared five distinct sampling regions in Sabah and Brunei. A three-level hierarchical F-analysis revealed high genetic differentiation among colonies within the same region, but low genetic differentiation within colonies or across regions. Overall levels of heterozygosity were unusually high (mean H(O) = 0.95, mean H(E) = 0.71) with two loci being entirely heterozygous, indicating an unusual reproductive system in this species. Bioassays revealed a negative correlation between relatedness and aggression, suggesting kinship as one factor facilitating supercolony formation in this species. Furthermore, we genotyped one individual per nest from Sabah (22 nests), Sarawak (one nest), Brunei (three nests) and the Philippines (two nests) using two mitochondrial DNA markers. We found six haplotypes, two of which included 82.1% of all sequences. Our study shows that the sampled area in Sabah consists of a mosaic of differently interrelated nests in different stages of colony establishment. While some of the sampled colonies may belong to large supercolonies, others are more likely to represent recently introduced or dispersed propagules that are just beginning to expand.
    Matched MeSH terms: Haplotypes/genetics
  13. Phylogeography and ethnogenesis of aboriginal Southeast Asians
    Hill C, Soares P, Mormina M, Macaulay V, Meehan W, Blackburn J, et al.
    Mol Biol Evol, 2006 Dec;23(12):2480-91.
    PMID: 16982817
    Studying the genetic history of the Orang Asli of Peninsular Malaysia can provide crucial clues to the peopling of Southeast Asia as a whole. We have analyzed mitochondrial DNA (mtDNAs) control-region and coding-region markers in 447 mtDNAs from the region, including 260 Orang Asli, representative of each of the traditional groupings, the Semang, the Senoi, and the Aboriginal Malays, allowing us to test hypotheses about their origins. All of the Orang Asli groups have undergone high levels of genetic drift, but phylogeographic traces nevertheless remain of the ancestry of their maternal lineages. The Semang have a deep ancestry within the Malay Peninsula, dating to the initial settlement from Africa >50,000 years ago. The Senoi appear to be a composite group, with approximately half of the maternal lineages tracing back to the ancestors of the Semang and about half to Indochina. This is in agreement with the suggestion that they represent the descendants of early Austroasiatic speaking agriculturalists, who brought both their language and their technology to the southern part of the peninsula approximately 4,000 years ago and coalesced with the indigenous population. The Aboriginal Malays are more diverse, and although they show some connections with island Southeast Asia, as expected, they also harbor haplogroups that are either novel or rare elsewhere. Contrary to expectations, complete mtDNA genome sequences from one of these, R9b, suggest an ancestry in Indochina around the time of the Last Glacial Maximum, followed by an early-Holocene dispersal through the Malay Peninsula into island Southeast Asia.
    Matched MeSH terms: Haplotypes/genetics
  14. Fulltext Phylogeographical pattern and evolutionary history of an important Peninsular Malaysian timber species, Neobalanocarpus heimii (Dipterocarpaceae)
    Tnah LH, Lee SL, Ng KK, Lee CT, Bhassu S, Othman RY
    J Hered, 2013 Jan-Feb;104(1):115-26.
    PMID: 23132907 DOI: 10.1093/jhered/ess076
    Tectonic movements, climatic oscillations, and marine transgressions during the Cenozoic have had a dramatic effect on the biota of the tropical rain forest. This study aims to reveal the phylogeography and evolutionary history of a Peninsular Malaysian endemic tropical timber species, Neobalanocarpus heimii (Dipterocarpaceae). A total of 32 natural populations of N. heimii, with 8 samples from each population were investigated. Fifteen haplotypes were identified from five noncoding chloroplast DNA (cpDNA) regions. Overall, two major genealogical cpDNA lineages of N. heimii were elucidated: a widespread southern and a northern region. The species is predicted to have survived in multiple refugia during climatic oscillations: the northwestern region (R1), the northeastern region (R2), and the southern region (R3). These putative glacial refugia exhibited higher levels of genetic diversity, population differentiation, and the presence of unique haplotypes. Recolonization of refugia R1 and R2 could have first expanded into the northern region and migrated both northeastwards and northwestwards. Meanwhile, recolonization of N. heimii throughout the southern region could have commenced from refugia R3 and migrated toward the northeast and northwest, respectively. The populations of Tersang, Pasir Raja, and Rotan Tunggal exhibited remarkably high haplotype diversity, which could have been the contact zones that have received an admixture of gene pools from the northerly and also southerly regions. As a whole, the populations of N. heimii derived from glacial refugia and contact zones should be considered in the conservation strategies in order to safeguard the long-term survival of the species.
    Matched MeSH terms: Haplotypes/genetics
  15. Fulltext PanSNPdb: the Pan-Asian SNP genotyping database
    Ngamphiw C, Assawamakin A, Xu S, Shaw PJ, Yang JO, Ghang H, et al.
    PLoS One, 2011;6(6):e21451.
    PMID: 21731755 DOI: 10.1371/journal.pone.0021451
    The HUGO Pan-Asian SNP consortium conducted the largest survey to date of human genetic diversity among Asians by sampling 1,719 unrelated individuals among 71 populations from China, India, Indonesia, Japan, Malaysia, the Philippines, Singapore, South Korea, Taiwan, and Thailand. We have constructed a database (PanSNPdb), which contains these data and various new analyses of them. PanSNPdb is a research resource in the analysis of the population structure of Asian peoples, including linkage disequilibrium patterns, haplotype distributions, and copy number variations. Furthermore, PanSNPdb provides an interactive comparison with other SNP and CNV databases, including HapMap3, JSNP, dbSNP and DGV and thus provides a comprehensive resource of human genetic diversity. The information is accessible via a widely accepted graphical interface used in many genetic variation databases. Unrestricted access to PanSNPdb and any associated files is available at: http://www4a.biotec.or.th/PASNP.
    Matched MeSH terms: Haplotypes/genetics*
  16. New insights into the haplotype diversity of the cosmopolitan cat flea Ctenocephalides felis (Siphonaptera: Pulicidae)
    Azrizal-Wahid N, Sofian-Azirun M, Low VL
    Vet Parasitol, 2020 May;281:109102.
    PMID: 32289653 DOI: 10.1016/j.vetpar.2020.109102
    The present study investigated the genetic profile of the cosmopolitan cat flea, Ctenocephalides felis (Siphonaptera: Pulicidae) from Malaysia and the reference data available in the National Center for Biotechnology Information (NCBI) GenBank. A set of sequences of 100 Malaysian samples aligned as 550 characters of the cytochrome c oxidase subunit I (cox1) and 706 characters of the II (cox2) genes revealed ten haplotypes (A1-A10) and eight haplotypes (B1-B8), respectively. The concatenated sequences of cox1 and cox2 genes with a total of 1256 characters revealed 15 haplotypes (AB1-AB15). Analyses indicated that haplotype AB1 was the most frequent and the most widespread haplotype in Malaysia. Overall haplotype and nucleotide diversities of the concatenated sequences were 0.52909 and 0.00424, respectively, with moderate genetic differentiation (FST = 0.17522) and high gene flow (Nm = 1.18). The western population presented the highest genetic diversity (Hd = 0.78333, Pi = 0.01269, Nh = 9), whereas the southern population demonstrated the lowest diversity (Hd = 0.15667, Pi = 0.00019, Nh = 3). The concatenated sequences showed genetic distances ranged from 0.08 % to 4.39 %. There were three aberrant haplotypes in cox2 sequences that highly divergent, suggesting the presence of cryptic species or occurrence of introgression. In the global point of view, the aligned sequences of C. felis revealed 65 haplotypes (AA1-AA65) by the cox1 gene (n = 586), and 27 haplotypes (BB1-BB27) by the cox2 gene (n = 204). Mapping of the haplotype network showed that Malaysian C. felis possesses seven unique haplotypes in both genes with the common haplotypes demonstrated genetic affinity with C. felis from Southeast Asia for cox1 and South America for cox2. The topologies of cox1 and cox2 phylogenetic trees were concordant with relevant grouping pattern of haplotypes in the network but revealed two major lineages by which Malaysian haplotypes were closely related with haplotypes from the tropical region.
    Matched MeSH terms: Haplotypes/genetics
  17. Fulltext Multi-platform discovery of haplotype-resolved structural variation in human genomes
    Chaisson MJP, Sanders AD, Zhao X, Malhotra A, Porubsky D, Rausch T, et al.
    Nat Commun, 2019 04 16;10(1):1784.
    PMID: 30992455 DOI: 10.1038/s41467-018-08148-z
    The incomplete identification of structural variants (SVs) from whole-genome sequencing data limits studies of human genetic diversity and disease association. Here, we apply a suite of long-read, short-read, strand-specific sequencing technologies, optical mapping, and variant discovery algorithms to comprehensively analyze three trios to define the full spectrum of human genetic variation in a haplotype-resolved manner. We identify 818,054 indel variants (<50 bp) and 27,622 SVs (≥50 bp) per genome. We also discover 156 inversions per genome and 58 of the inversions intersect with the critical regions of recurrent microdeletion and microduplication syndromes. Taken together, our SV callsets represent a three to sevenfold increase in SV detection compared to most standard high-throughput sequencing studies, including those from the 1000 Genomes Project. The methods and the dataset presented serve as a gold standard for the scientific community allowing us to make recommendations for maximizing structural variation sensitivity for future genome sequencing studies.
    Matched MeSH terms: Haplotypes/genetics*
  18. Molecular basis of beta-thalassemia in the Maldives
    Furuumi H, Firdous N, Inoue T, Ohta H, Winichagoon P, Fucharoen S, et al.
    Hemoglobin, 1998 Mar;22(2):141-51.
    PMID: 9576331
    We have systematically analyzed beta-thalassemia genes using polymerase chain reaction-related techniques, dot-blot hybridization with oligonucleotide probes, allele specific-polymerase chain reaction, and sequencing of amplified DNA fragments from 41 unrelated patients, including 37 beta-thalassemia homozygotes, three with beta-thalassemia/Hb E, and one with beta-thalassemia/Hb S. Four different beta-thalassemia mutations were detected in 78 alleles. These are the IVS-I-5 (G-->C), codon 30 (AGG-->ACG) [also indicated as IVS-I (-1)], IVS-I-1 (G-->A), and codons 41/42 (-TTCT) mutations. The distribution of the beta-thalassemia mutations in the Maldives is 58 alleles (74.3%) with the IVS-I-5 (G-->C) mutation, 12 (15.4%) with the codon 30 (AGG-->ACG) mutation, seven (9%) with the IVS-I-1 (G-->A) mutation, and one with the codons 41/42 (-TTCT) mutation. The first three mutations account for 98.7% of the total number of beta-thalassemia chromosomes studied. These mutations are clustered in the region spanning 6 bp around the junction of exon 1 and the first intervening sequence of the beta-globin gene. These observations have significant implications for setting up a thalassemia prevention and control program in the Maldives. Analysis of haplotypes and frameworks of chromosomes bearing each beta-thalassemia mutation suggested that the origin and spread of these mutations were reflected by the historical record.
    Matched MeSH terms: Haplotypes/genetics
  19. Mitochondrial DNA diversity in Southeast Asian populations
    Schurr TG, Wallace DC
    Hum Biol, 2002 Jun;74(3):431-52.
    PMID: 12180765
    In a previous study of Southeast Asian genetic variation, we characterized mitochondrial DNAs (mtDNAs) from six populations through high-resolution restriction fragment length polymorphism (RFLP) analysis. Our analysis revealed that these Southeast Asian populations were genetically similar to each other, suggesting they had a common origin. However, other patterns of population associations also emerged. Haplotypes from a major founding haplogroup in Papua New Guinea were present in Malaysia; the Vietnamese and Malaysian aborigines (Orang Asli) had high frequencies of haplogroup F, which was also seen in most other Southeast Asian populations; and haplogroup B, defined by the Region V 9-base-pair deletion, was present throughout the region. In addition, the Malaysian and Sabah (Borneo) aborigine populations exhibited a number of unique mtDNA clusters that were not observed in other populations. Unfortunately, it has been difficult to compare these patterns of genetic diversity with those shown in subsequent studies of mtDNA variation in Southeast Asian populations because the latter have typically sequenced the first hypervariable segment (HVS-I) of the control region (CR) sequencing rather than used RFLP haplotyping to characterize the mtDNAs present in them. For this reason, we sequenced the HVS-I of Southeast Asian mtDNAs that had previously been subjected to RFLP analysis, and compared the resulting data with published information from other Southeast Asian and Oceanic groups. Our findings reveal broad patterns of mtDNA haplogroup distribution in Southeast Asia that may reflect different population expansion events in this region over the past 50,000-5,000 years.
    Matched MeSH terms: Haplotypes/genetics*
  20. Fulltext Low levels of polymorphisms and no evidence for diversifying selection on the Plasmodium knowlesi Apical Membrane Antigen 1 gene
    Faber BW, Abdul Kadir K, Rodriguez-Garcia R, Remarque EJ, Saul FA, Vulliez-Le Normand B, et al.
    PLoS One, 2015;10(4):e0124400.
    PMID: 25881166 DOI: 10.1371/journal.pone.0124400
    Infection with Plasmodium knowlesi, a zoonotic primate malaria, is a growing human health problem in Southeast Asia. P. knowlesi is being used in malaria vaccine studies, and a number of proteins are being considered as candidate malaria vaccine antigens, including the Apical Membrane Antigen 1 (AMA1). In order to determine genetic diversity of the ama1 gene and to identify epitopes of AMA1 under strongest immune selection, the ama1 gene of 52 P. knowlesi isolates derived from human infections was sequenced. Sequence analysis of isolates from two geographically isolated regions in Sarawak showed that polymorphism in the protein is low compared to that of AMA1 of the major human malaria parasites, P. falciparum and P. vivax. Although the number of haplotypes was 27, the frequency of mutations at the majority of the polymorphic positions was low, and only six positions had a variance frequency higher than 10%. Only two positions had more than one alternative amino acid. Interestingly, three of the high-frequency polymorphic sites correspond to invariant sites in PfAMA1 or PvAMA1. Statistically significant differences in the quantity of three of the six high frequency mutations were observed between the two regions. These analyses suggest that the pkama1 gene is not under balancing selection, as observed for pfama1 and pvama1, and that the PkAMA1 protein is not a primary target for protective humoral immune responses in their reservoir macaque hosts, unlike PfAMA1 and PvAMA1 in humans. The low level of polymorphism justifies the development of a single allele PkAMA1-based vaccine.
    Matched MeSH terms: Haplotypes/genetics*
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