Exome sequencing of liver fluke-associated cholangiocarcinoma

Opisthorchis viverrini-related cholangiocarcinoma (CCA), a fatal bile duct cancer, is a major public health concern in areas endemic for this parasite. We report here whole-exome sequencing of eight O. viverrini-related tumors and matched normal tissue. We identified and validated 206 somatic mutations in 187 genes using Sanger sequencing and selected 15 genes for mutation prevalence screening in an additional 46 individuals with CCA (cases). In addition to the known cancer-related genes TP53 (mutated in 44.4% of cases), KRAS (16.7%) and SMAD4 (16.7%), we identified somatic mutations in 10 newly implicated genes in 14.8-3.7% of cases. These included inactivating mutations in MLL3 (in 14.8% of cases), ROBO2 (9.3%), RNF43 (9.3%) and PEG3 (5.6%), and activating mutations in the GNAS oncogene (9.3%). These genes have functions that can be broadly grouped into three biological classes: (i) deactivation of histone modifiers, (ii) activation of G protein signaling and (iii) loss of genome stability. This study provides insight into the mutational landscape contributing to O. viverrini-related CCA.     

The global distribution of clinical episodes of Plasmodium falciparum malaria

Interest in mapping the global distribution of malaria is motivated by a need to define populations at risk for appropriate resource allocation and to provide a robust framework for evaluating its global economic impact. Comparison of older and more recent malaria maps shows how the disease has been geographically restricted, but it remains entrenched in poor areas of the world with climates suitable for transmission. Here we provide an empirical approach to estimating the number of clinical events caused by Plasmodium falciparum worldwide, by using a combination of epidemiological, geographical and demographic data. We estimate that there were 515 (range 300-660) million episodes of clinical P. falciparum malaria in 2002. These global estimates are up to 50% higher than those reported by the World Health Organization (WHO) and 200% higher for areas outside Africa, reflecting the WHO's reliance upon passive national reporting for these countries. Without an informed understanding of the cartography of malaria risk, the global extent of clinical disease caused by P. falciparum will continue to be underestimated.     

Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations

Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function-related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function-related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10(-8)). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ～110,347 individuals. We identify pleiotropic associations among these loci with kidney function-related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.     

化学发光法检测苹果汁中的对羟基苯甲酸

在硫酸介质中,对羟基苯甲酸对铈(Ⅳ)-罗丹明6G的化学发光反应有较强的增敏作用,据此建立了测定对羟基苯甲酸的反相高效液相色谱-化学发光新方法.该方法测定对羟基苯甲酸的检出限为3.1×10-10g/mL,方法的线性范围为2.0×10-9～5.0×10-7g/mL,对于1.0×10-8g/mL对羟基苯甲酸11次平行测定的相对标准偏差为1.42%.该方法灵敏度高、线性范围宽,已成功地应用于苹果汁样品中对羟基苯甲酸的含量分析.     

Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci

We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 × 10(-8) to P = 1.9 × 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 × 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.     

Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians

We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.     

Phylogenetic taxonomy of Hemiphyllodactylus Bleeker, 1860 (Squamata: Gekkonidae) with descriptions of three new species from Myanmar

ABSTRACT

A phylogenetic taxonomy of the gekkonid genus Hemiphyllodactylus based on molecular, morphological, and ecological data recovered 28 species, including three new species from the upland regions of the Shan Plateau in eastern Myanmar. Hemiphyllodactylus linnwayensis sp. nov. is a forest-adapted species that may also be a human commensal and H. montawaensis sp. nov. and H. tonywhitteni sp. nov. are karst forest-adapted species. The discovery of three new species from montane regions in eastern Myanmar extends the distribution of a larger monophyletic group of Hemiphyllodactylus westward to the eastern edge of the Ayeyrawady Basin through a series of semi-contiguous, parallel mountain ranges originating in western China and northern Thailand. The discovery of the karst forest-adapted H. montawaensis sp. nov. and H. tonywhitteni sp. nov. further emphasizes the unrealized herpetological diversity endemic to karst ecosystems and the need for increased field work throughout such habitats in South-East Asia.

www.zoobank.org/urn:lsid:zoobank.org:pub:E42FA075-E8E0-4005-98AB-12E8D5F23A07     

Mutations in sodium-borate cotransporter SLC4A11 cause recessive congenital hereditary endothelial dystrophy (CHED2)

Congenital hereditary endothelial dystrophy (CHED) is a heritable, bilateral corneal dystrophy characterized by corneal opacification and nystagmus. We describe seven different mutations in the SLC4A11 gene in ten families with autosomal recessive CHED. Mutations in SLC4A11, which encodes a membrane-bound sodium-borate cotransporter, cause loss of function of the protein either by blocking its membrane targeting or nonsense-mediated decay.     

Three more new species of Cyrtodactylus (Squamata: Gekkonidae) from the Salween Basin of eastern Myanmar underscore the urgent need for the conservation of karst habitats

An integrative phylogenetic taxonomic analysis recovers three additional new species of karst-associated Cyrtodactylus Gray (Squamata: Gekkonidae) – C. bayinnyiensis sp. nov., C. chaunghanakwaensis sp. nov. and C. naungkayaingensis sp. nov. – from a narrow zone in the Salween Basin of Kayin and Mon states in eastern Myanmar from which nine new species were recently described. This degree of unprecedented diversity and site-specific endemism will no doubt continue to rise when at least 44 unsurveyed karstic habitat-islands in this same area are also explored. These data indicate that karst habitats not only serve as foci for speciation, but their rugged terrain spares them from agricultural development and, as such, they are the only habitats in the Salween Basin wherein much of the pre-agricultural herpetofauna can survive. This continues to underscore the fact that karst habitats in Myanmar harbour a significant portion of that country’s herpetofauna, some of which remains undescribed. Despite eastern Myanmar constituting some of the most extensive karstic regions in South-east Asia, they are the least legally protected, with only 1% of their terrain recognised as vulnerable. Until karst habitats in Myanmar are thoroughly investigated, a significant portion of this country’s herpetological diversity will remain underestimated and unprotected. Therefore, issues associated with karst conservation and management in Myanmar should be elevated to a new level of urgency.