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51.
Xuanyao Liu Rick?Twee-Hee Ong Esakimuthu?Nisha Pillai Abier?M. Elzein Kerrin?S. Small Taane?G. Clark Dominic?P. Kwiatkowski Yik-Ying Teo 《American journal of human genetics》2013,92(6):866-881
Natural selection is a significant force that shapes the architecture of the human genome and introduces diversity across global populations. The question of whether advantageous mutations have arisen in the human genome as a result of single or multiple mutation events remains unanswered except for the fact that there exist a handful of genes such as those that confer lactase persistence, affect skin pigmentation, or cause sickle cell anemia. We have developed a long-range-haplotype method for identifying genomic signatures of positive selection to complement existing methods, such as the integrated haplotype score (iHS) or cross-population extended haplotype homozygosity (XP-EHH), for locating signals across the entire allele frequency spectrum. Our method also locates the founder haplotypes that carry the advantageous variants and infers their corresponding population frequencies. This presents an opportunity to systematically interrogate the whole human genome whether a selection signal shared across different populations is the consequence of a single mutation process followed subsequently by gene flow between populations or of convergent evolution due to the occurrence of multiple independent mutation events either at the same variant or within the same gene. The application of our method to data from 14 populations across the world revealed that positive-selection events tend to cluster in populations of the same ancestry. Comparing the founder haplotypes for events that are present across different populations revealed that convergent evolution is a rare occurrence and that the majority of shared signals stem from the same evolutionary event. 相似文献
52.
Lai-Ping Wong Rick?Twee-Hee Ong Wan-Ting Poh Xuanyao Liu Peng Chen Ruoying Li Kevin?Koi-Yau Lam Nisha?Esakimuthu Pillai Kar-Seng Sim Haiyan Xu Ngak-Leng Sim Shu-Mei Teo Jia-Nee Foo Linda?Wei-Lin Tan Yenly Lim Seok-Hwee Koo Linda?Seo-Hwee Gan Ching-Yu Cheng Sharon Wee Eric?Peng-Huat Yap Pauline?Crystal Ng Wei-Yen Lim Richie Soong Markus?Rene Wenk Tin Aung Tien-Yin Wong Chiea-Chuen Khor Peter Little Kee-Seng Chia Yik-Ying Teo 《American journal of human genetics》2013,92(1):52-66
Whole-genome sequencing across multiple samples in a population provides an unprecedented opportunity for comprehensively characterizing the polymorphic variants in the population. Although the 1000 Genomes Project (1KGP) has offered brief insights into the value of population-level sequencing, the low coverage has compromised the ability to confidently detect rare and low-frequency variants. In addition, the composition of populations in the 1KGP is not complete, despite the fact that the study design has been extended to more than 2,500 samples from more than 20 population groups. The Malays are one of the Austronesian groups predominantly present in Southeast Asia and Oceania, and the Singapore Sequencing Malay Project (SSMP) aims to perform deep whole-genome sequencing of 100 healthy Malays. By sequencing at a minimum of 30× coverage, we have illustrated the higher sensitivity at detecting low-frequency and rare variants and the ability to investigate the presence of hotspots of functional mutations. Compared to the low-pass sequencing in the 1KGP, the deeper coverage allows more functional variants to be identified for each person. A comparison of the fidelity of genotype imputation of Malays indicated that a population-specific reference panel, such as the SSMP, outperforms a cosmopolitan panel with larger number of individuals for common SNPs. For lower-frequency (<5%) markers, a larger number of individuals might have to be whole-genome sequenced so that the accuracy currently afforded by the 1KGP can be achieved. The SSMP data are expected to be the benchmark for evaluating the value of deep population-level sequencing versus low-pass sequencing, especially in populations that are poorly represented in population-genetics studies. 相似文献
53.
C. Brown D. F. R. P. Burslem J. B. Illian L. Bao W. Brockelman M. Cao L. W. Chang H. S. Dattaraja S. Davies C. V. S. Gunatilleke I. A. U. N. Gunatilleke J. Huang A. R. Kassim J. V. LaFrankie J. Lian L. Lin K. Ma X. Mi A. Nathalang S. Noor P. Ong R. Sukumar S. H. Su I. F. Sun H. S. Suresh S. Tan J. Thompson M. Uriarte R. Valencia S. L. Yap W. Ye R. Law 《Proceedings. Biological sciences / The Royal Society》2013,280(1764)
Neutral and niche theories give contrasting explanations for the maintenance of tropical tree species diversity. Both have some empirical support, but methods to disentangle their effects have not yet been developed. We applied a statistical measure of spatial structure to data from 14 large tropical forest plots to test a prediction of niche theory that is incompatible with neutral theory: that species in heterogeneous environments should separate out in space according to their niche preferences. We chose plots across a range of topographic heterogeneity, and tested whether pairwise spatial associations among species were more variable in more heterogeneous sites. We found strong support for this prediction, based on a strong positive relationship between variance in the spatial structure of species pairs and topographic heterogeneity across sites. We interpret this pattern as evidence of pervasive niche differentiation, which increases in importance with increasing environmental heterogeneity. 相似文献
54.
55.
Kim Tien Ng Lai Yee Ong Sin How Lim Yutaka Takebe Adeeba Kamarulzaman Kok Keng Tee 《PloS one》2013,8(6)
HIV-1 epidemics among men who have sex with men (MSM) continue to expand in developed and developing countries. Although HIV infection in MSM is amongst the highest of the key affected populations in many countries in Southeast Asia, comprehensive molecular epidemiological study of HIV-1 among MSM remains inadequate in the region including in Malaysia. Here, we reported the phylodynamic profiles of HIV-1 genotypes circulating among MSM population in Kuala Lumpur, Malaysia. A total of n = 459 newly-diagnosed treatment-naïve consenting subjects were recruited between March 2006 and August 2012, of whom 87 (18.9%) were self-reported MSM. Transmitted drug resistance mutations were absent in these isolates. Cumulatively, phylogenetic reconstructions of the pro-rt gene (HXB2∶2253–3275) showed that HIV-1 subtype B and CRF01_AE were predominant and contributed to approximately 80% of the total HIV-1 infection among MSM. In addition to numerous unique transmission lineages within these genotypes, twelve monophyletic transmission clusters of different sizes (2–7 MSM sequences, supported by posterior probability value of 1) were identified in Malaysia. Bayesian coalescent analysis estimated that the divergence times for these clusters were mainly dated between 1995 and 2005 with four major transmission clusters radiating at least 12 years ago suggesting that active spread of multiple sub-epidemic clusters occurred during this period. The changes in effective population size of subtype B showed an exponential growth within 5 years between 1988 and 1993, while CRF01_AE lineage exhibited similar expansion between 1993 and 2003. Our study provides the first insight of the phylodynamic profile of HIV-1 subtype B and CRF01_AE circulating among MSM population in Kuala Lumpur, Malaysia, unravelling the importance of understanding transmission behaviours as well as evolutionary history of HIV-1 in assessing the risk of outbreak or epidemic expansion. 相似文献
56.
Xiao Wei Xin Chen Xia Wang Weiwei Zheng Dong Zhang Dajun Tian Songhui Jiang Choon Nam Ong Gengsheng He Weidong Qu 《PloS one》2013,8(3)
Drinking water chlorination plays a pivotal role in preventing pathogen contamination against water-borne disease. However, chemical disinfection leads to the formation of halogenated disinfection by products (DBPs). Many DBPs are highly toxic and are of health concern. In this study, we conducted a comprehensive measurements of DBPs, including iodoacetic acid (IAA), iodoform (IF), nine haloacetic acids and four trihalomethanes in drinking waters from 13 water plants in Shanghai, China. The results suggested that IAA and IF were found in all the water treatment plants, with maximum levels of 1.66 µg/L and 1.25 µg/L for IAA and IF, respectively. Owing to deterioration of water quality, the Huangpu River has higher IAA and IF than the Yangtze River. Our results also demonstrated that low pH, high natural organic matter, ammonia nitrogen, and iodide in source waters increased IAA and IF formation. Compared to chlorine, chloramines resulted in higher concentration of iodinated DBP, but reduced the levels of trihalomethanes. This is the first study to reveal the widespread occurrence of IAA and IF in drinking water in China. The data provide a better understanding on the formation of iodinated disinfection byproducts and the findings should be useful for treatment process improvement and disinfection byproducts controls. 相似文献
57.
Kristina S. Sobotka Stuart B. Hooper Kelly J. Crossley Tracey Ong Georg M. Schm?lzer Samantha K. Barton Annie R. A. McDougall Suzie L. Miller Mary Tolcos Claus Klingenberg Graeme R. Polglase 《PloS one》2016,11(1)
BackgroundA sustained inflation (SI) rapidly restores cardiac function in asphyxic, bradycardic newborns but its effects on cerebral haemodynamics and brain injury are unknown. We determined the effect of different SI strategies on carotid blood flow (CaBF) and cerebral vascular integrity in asphyxiated near-term lambs.MethodsLambs were instrumented and delivered at 139 ± 2 d gestation and asphyxia was induced by delaying ventilation onset. Lambs were randomised to receive 5 consecutive 3 s SI (multiple SI; n = 6), a single 30 s SI (single SI; n = 6) or conventional ventilation (no SI; n = 6). Ventilation continued for 30 min in all lambs while CaBF and respiratory function parameters were recorded. Brains were assessed for gross histopathology and vascular leakage.ResultsCaBF increased more rapidly and to a greater extent during a single SI (p = 0.01), which then decreased below both other groups by 10 min, due to a higher cerebral oxygen delivery (p = 0.01). Blood brain barrier disruption was increased in single SI lambs as indicated by increased numbers of blood vessel profiles with plasma protein extravasation (p = 0.001) in the cerebral cortex. There were no differences in CaBF or cerebral oxygen delivery between the multiple SI and no SI lambs.ConclusionsVentilation with an initial single 30 s SI improves circulatory recovery, but is associated with greater disruption of blood brain barrier function, which may exacerbate brain injury suffered by asphyxiated newborns. This injury may occur as a direct result of the initial SI or to the higher tidal volumes delivered during subsequent ventilation. 相似文献
58.
Trey K. Sato Mary Tremaine Lucas S. Parreiras Alexander S. Hebert Kevin S. Myers Alan J. Higbee Maria Sardi Sean J. McIlwain Irene M. Ong Rebecca J. Breuer Ragothaman Avanasi Narasimhan Mick A. McGee Quinn Dickinson Alex La Reau Dan Xie Mingyuan Tian Jeff S. Piotrowski Jennifer L. Reed Yaoping Zhang Joshua J. Coon Chris Todd Hittinger Audrey P. Gasch Robert Landick 《PLoS genetics》2016,12(11)
59.
Yilong Fu Lai-Chun Ong Sudhir H. Ranganath Lin Zheng Irene Kee Wenbo Zhan Sidney Yu Pierce K. H. Chow Chi-Hwa Wang 《PloS one》2016,11(2)
Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using 18F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as 18F-Fluorocholine (18F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives. In this study, the potential application of a dual tracer 18F-FCH/18F-FDG-PET is investigated in order to improve the sensitivity of PET imaging for low grade glioma diagnosis based on a mouse orthotopic xenograft model. BALB/c nude mice with and without orthotopic glioma xenografts from U87 MG-luc2 glioma cell line are used for the study. The animals are subjected to 18F-FCH and 18F-FDG PET imaging, and images acquired from two separate scans are superimposed for analysis. The 18F-FCH counts are subtracted from the merged images to identify the tumor. Micro-CT, bioluminescence imaging (BLI), histology and measurement of the tumor diameter are also conducted for comparison. Results show that there is a significant contrast in 18F-FCH uptake between tumor and normal brain tissue (2.65 ± 0.98), but with a high false positive rate of 28.6%. The difficulty of identifying the tumor by 18F-FDG only is also proved in this study. All the tumors can be detected based on the dual tracer technique of 18F-FCH/ 18F-FDG-PET imaging in this study, while the false-positive caused by 18F-FCH can be eliminated. Dual tracer 18F-FCH/18F-FDG PET imaging has the potential to improve the visualization of low grade glioma. 18F-FCH delineates tumor areas and the tumor can be identified by subtracting the 18F-FCH counts. The sensitivity was over 95%. Further studies are required to evaluate the possibility of applying this technique in clinical trials. 相似文献
60.
Fatiha Tabet Luisa F. Cuesta Torres Kwok Leung Ong Sudichhya Shrestha Sébastien A. Choteau Philip J. Barter Peter Clifton Kerry-Anne Rye 《PloS one》2016,11(3)