Whole exome sequencing identifies a novel splice-site mutation in ADAMTS17 in an Indian family with Weill-Marchesani syndrome

Purpose: Weill-Marchesani syndrome (WMS) is a rare connective tissue disorder, characterized by short stature, micro-spherophakic lens, and stubby hands and feet (brachydactyly). WMS is caused by mutations in the FBN1, ADAMTS10, and LTBP2 genes. Mutations in the LTBP2 and ADAMTS17 genes cause a WMS-like syndrome, in which the affected individuals show major features of WMS but do not display brachydactyly and joint stiffness. The main purpose of our study was to determine the genetic cause of WMS in an Indian family. Methods: Whole exome sequencing (WES) was used to identify the genetic cause of WMS in the family. The cosegregation of the mutation was determined with Sanger sequencing. Reverse transcription (RT)-PCR analysis was used to assess the effect of a splice-site mutation on splicing of the ADAMTS17 transcript. Results: The WES analysis identified a homozygous novel splice-site mutation c.873+1G>T in a known WMS-like syndrome gene, ADAMTS17, in the family. RT-PCR analysis in the patient showed that exon 5 was skipped, which resulted in the deletion of 28 amino acids in the ADAMTS17 protein. Conclusions: The mutation in the WMS-like syndrome gene ADAMTS17 also causes WMS in an Indian family. The present study will be helpful in genetic diagnosis of this family and increases the number of mutations of this gene to six.

Slow Slip Acceleration beneath Andaman Islands Triggered by the 11 April 2012 Indian Ocean Earthquakes

The M-w 8.6 and 8.2 strike-slip earthquakes that struck the northeast Indian Ocean on 11 April 2012 resulted in coseismic deformation both at near and distant sites. The slip distribution, deduced using seismic-wave analysis for the orthogonal faults that ruptured during these earthquakes, is sufficient to predict the coseismic displacements at the Global Positioning System (GPS) sites, such as NTUS, PALK, and CUSV, but fall short at four continuous sites in the Andaman Islands region. Slip modeling, for times prior to the events, suggests that the lower portion of the thrust fault beneath the Andaman Islands has been slipping at least at the rate of 40 cm/yr, in response to the 2004 Sumatra-Andaman coseismic stress change. Modeling of GPS displacements suggests that the en echelon and orthogonal fault ruptures of the 2012 intraplate oceanic earthquakes could have possibly accelerated the ongoing slow slip, along the lower portion of the thrust fault beneath the islands with a month-long slip of 4-10 cm. The misfit to the coseismic GPS displacements along the Andaman Islands could be improved with a better source model, assuming that no local process contributed to this anomaly.

Cryptic species and Miocene diversification of Palaearctic naked-toed geckos (Squamata: Gekkonidae) in the Indian dry zone

We sampled Palaearctic naked-toed geckos from across their range in India and used two mitochondrial and two nuclear genes to reconstruct relationships within a global phylogeny. Published sequences of Peninsular Indian Hemidactylus allow us to contrast these two groups in dating analyses - providing insights into the history of the Indian dry zone. Palaearctic naked-toed geckos first moved onto the Indian Plate in the Oligocene, with higher-level diversification probably linked to collision of the Indian and Eurasian plates, and subsequent dispersal into-India and diversification with increasing Miocene aridity. An independent gekkonid radiation with species in the dry zone, Hemidactylus diversified during the same period in Peninsular India. Our results demonstrate that dry zone taxa across India may date back to at least the Miocene, with a potential historical climatic barrier between the Indus and Peninsular Indian Divisions. `Cyrtopodion' aravallense is revealed to be a complex with seven genetically and environmentally divergent lineages that began diversifying in the late Miocene, congruent with increased aridity in north-western India. This discovery of cryptic diversity in the Indian dry zone represents the first terrestrial vertebrate radiation from north-western central India and highlights how little we understand of the regions' biodiversity, emphasizing the need for systematic geographic sampling and multiline evidence to reveal true patterns of diversity. The ancestor of `Cyrtopodion' aravallense came into the nascent Indian dry zone in the Miocene and has since diversified, potentially in the absence of any sympatric scansorial rupicolous geckos. Cyrtopodion scabrum represents a unique case of commensalism and shows phylogeographic structure in its presumed native range. The taxonomic implications of our study include a number of undescribed species, recognition of `Cyrtopodion' as a distinct lineage and the non-monophyly of Altiphylax.

Non-polio enterovirus association with persistent diarrhea in children as revealed by a follow-up study of an Indian cohort during the first two years of life

Background: We recently reported significant association of non-polio enteroviruses (NPEVs) with acute diarrhea in children. Persistent diarrhea (PD) remains a major cause of morbidity and mortality in infants below two years of age in developing countries. Understanding age-dependent frequency and duration of NPEV infections is important to determine their association with persistent diarrhea and disease burden. Objectives: A cohort of 140 infants was followed for 6 months to 2 years of age to determine the frequency, duration, and association with PD of NPEV infections in comparison with rotavirus and other agents. Study design: Stool samples were collected every 14 days, and diarrheal episodes and their duration were recorded. Enteroviruses were characterized by RT-PCR and VP1 gene sequence analysis, rotavirus by electropherotyping, and other agents by PCR. Results: Of 4545 samples, negative for oral polio vaccine strains, 3907 (85.96%) and 638 (14.04%) were NPEV-negative and NPEV-positive, respectively, representing 403 (8.87%) infection episodes. About 68% of NPEV infections occurred during the first year with every child having at least one episode lasting between four days and four months. Approximately 38% and 22% of total diarrheal episodes were positive for NPEV and RV, respectively. While about 18% of NPEV infection episodes were associated with diarrhea, 6% being persistent, 13% of total diarrheal episodes were persistent involving infections by monotype NPEV strains or sequential infections by multiple strains and other agents. Conclusions: This is the first report revealing NPEVs as the single most frequently and persistently detected viral pathogen in every PD episode. (C) 2014 Elsevier B.V. All rights reserved.

Sheltered coastal environments as archives of paleo-tsunami deposits: Observations from the 2004 Indian Ocean tsunami

The 2004 earthquake left several traces of coseismic land deformation and tsunami deposits, both on the islands along the plate boundary and distant shores of the Indian Ocean rim countries. Researchers are now exploring these sites to develop a chronology of past events. Where the coastal regions are also inundated by storm surges, there is an additional challenge to discriminate between the deposits formed by these two processes. Paleo-tsunami research relies largely on finding deposits where preservation potential is high and storm surge origin can be excluded. During the past decade of our work along the Andaman and Nicobar Islands and the east coast of India, we have observed that the 2004 tsunami deposits are best preserved in lagoons, inland streams and also on elevated terraces. Chronological evidence for older events obtained from such sites is better correlated with those from Thailand, Sri Lanka and Indonesia, reiterating their usefulness in tsunami geology studies. (C) 2014 Elsevier Ltd. All rights reserved.

Whole exome sequencing in an Indian family links Coats plus syndrome and dextrocardia with a homozygous novel CTC1 and a rare HES7 variation

Background: Coats plus syndrome is an autosomal recessive, pleiotropic, multisystem disorder characterized by retinal telangiectasia and exudates, intracranial calcification with leukoencephalopathy and brain cysts, osteopenia with predisposition to fractures, bone marrow suppression, gastrointestinal bleeding and portal hypertension. It is caused by compound heterozygous mutations in the CTC1 gene. Case presentation: We encountered a case of an eight-year old boy from an Indian family with manifestations of Coats plus syndrome along with an unusual occurrence of dextrocardia and situs inversus. Targeted resequencing of the CTC1 gene as well as whole exome sequencing (WES) were conducted in this family to identify the causal variations. The identified candidate variations were screened in ethnicity matched healthy controls. The effect of CTC1 variation on telomere length was assessed using Southern blot. A novel homozygous missense mutation c.1451A > C (p.H484P) in exon 9 of the CTC1 gene and a rare 3'UTR known dbSNP variation (c.*556 T > C) in HES7 were identified as the plausible candidates associated with this complex phenotype of Coats plus and dextrocardia. This CTC1 variation was absent in the controls and we also observed a reduced telomere length in the affected individual's DNA, suggesting its likely pathogenic nature. The reported p.H484P mutation is located in the N-terminal 700 amino acid regionthat is important for the binding of CTC1 to ssDNA through its two OB domains. WES data also showed a rare homozygous missense variation in the TEK gene in the affected individual. Both HES7 and TEK are targets of the Notch signaling pathway. Conclusions: This is the first report of a genetically confirmed case of Coats plus syndrome from India. By means of WES, the genetic variations in this family with unique and rare complex phenotype could be traced effectively. We speculate the important role of Notch signaling in this complex phenotypic presentation of Coats plus syndrome and dextrocardia. The present finding will be useful for genetic diagnosis and carrier detection in the family and for other patients with similar disease manifestations.

Performance evaluation of AR4 Climate Models in simulating daily precipitation over the Indian region using skill scores

The ability of Coupled General Circulation Models (CGCMs) participating in the Intergovernmental Panel for Climate Change's fourth assessment report (IPCC AR4) for the 20th century climate (20C3M scenario) to simulate the daily precipitation over the Indian region is explored. The skill is evaluated on a 2.5A degrees x 2.5A degrees grid square compared with the Indian Meteorological Department's (IMD) gridded dataset, and every GCM is ranked for each of these grids based on its skill score. Skill scores (SSs) are estimated from the probability density functions (PDFs) obtained from observed IMD datasets and GCM simulations. The methodology takes into account (high) extreme precipitation events simulated by GCMs. The results are analyzed and presented for three categories and six zones. The three categories are the monsoon season (JJASO - June to October), non-monsoon season (JFMAMND - January to May, November, December) and for the entire year (''Annual''). The six precipitation zones are peninsular, west central, northwest, northeast, central northeast India, and the hilly region. Sensitivity analysis was performed for three spatial scales, 2.5A degrees grid square, zones, and all of India, in the three categories. The models were ranked based on the SS. The category JFMAMND had a higher SS than the JJASO category. The northwest zone had higher SSs, whereas the peninsular and hilly regions had lower SS. No single GCM can be identified as the best for all categories and zones. Some models consistently outperformed the model ensemble, and one model had particularly poor performance. Results show that most models underestimated the daily precipitation rates in the 0-1 mm/day range and overestimated it in the 1-15 mm/day range.

Molecules support morphology: species status of South Indian populations of the widely distributed Hanuman langur

The taxonomy of the Hanuman langur (Semnopithecus spp.), a widely distributed Asian colobine monkey, has been in a flux for a long time due to much disagreement between various classification schemes. However, results from a recent field-based morphological study were consistent with Hill's (Ceylon J Sci 21:277-305, 1939) species level classification scheme. Here we tested the validity of S. hypoleucos and S. priam, the two South Indian species recognized by Hill. To this end, one mitochondrial and four nuclear markers were sequenced from over 72 non-invasive samples of Hanuman langurs and S. johnii collected from across India. The molecular data were subjected to various tree building methods. The nuclear data was also used in a Bayesian structure analysis and to determine the genealogical sorting index of each hypothesized species. Results from nuclear data suggest that the South Indian population of Hanuman langur consists of two units that correspond to the species recognized by Hill. However in the mitochondrial tree S. johnii and S. priam were polyphyletic probably due to retention of ancestral polymorphism and/or low levels of hybridization. Implications of these results on conservation of Hanuman langurs are also discussed.

Sun skink diversification across the Indian-Southeast Asian biogeographical interface

Aim Widespread, transcontinental vertebrate groups represent ideal systems for biogeographical studies, because they can shed light on a wide range of questions relating to species diversification across the geographical template. We combined extensive geographical and genetic sampling from across multiple biogeographical realms to examine the timing and location of diversification in Asian sun skinks, a clade characterized by problematic species boundaries and a particularly enigmatic evolutionary history. Location Indian subcontinent, the Philippines, Southeast Asia and Sundaland. Methods We sequenced one mitochondrial and nine nuclear genes for most species in the genus Eutropis, and estimated phylogenetic relationships and divergence times using coalescent methods. To investigate the location of diversification events, we also estimated ancestral geographical ranges using several methods. Finally, we explored patterns of genetic diversity within several poorly understood, but widely distributed species. Results Divergence-time estimates indicate that Eutropis began to diversify during the Eocene. Biogeographical reconstructions show that species diversification was associated with dispersal into three biogeographical realms: India, Sundaland and the Philippines. Main conclusions The results of this study clarify several questions related to the evolutionary history of Eutropis, and place them in the context of classic Southeast Asian biogeography. Our study represents one of the first to compile a heavily sampled multilocus dataset ranging across international boundaries in southern Asia that have historically prevented a unified understanding of biogeographical and evolutionary processes involving the Indian subcontinent, mainland southern Asia and the island archipelagos of Southeast Asia.

Benchmarking sustainability of Indian electricity system: An indicator approach

India needs to significantly increase its electricity consumption levels, in a sustainable manner, if it has to ensure rapid economic development, a goal that remains the most potent tool for delivering adaptation capacity to its poor who will suffer the worst consequences of climate change. Resource/supply constraints faced by conventional energy sources, techno-economic constraints faced by renewable energy sources, and the bounds imposed by climate change on fossil fuel use are likely to undermine India's quest for having a robust electricity system that can effectively contribute to achieving accelerated, sustainable and inclusive economic growth. One possible way out could be transitioning into a sustainable electricity system, which is a trade-off solution having taken into account the economic, social and environmental concerns. As a first step toward understanding this transition, we contribute an indicator based hierarchical multidimensional framework as an analytical tool for sustainability assessment of electricity systems, and validate it for India's national electricity system. We evaluate Indian electricity system using this framework by comparing it with a hypothetical benchmark sustainable electrical system, which was created using best indicator values realized across national electricity systems in the world. This framework, we believe, can be used to examine the social, economic and environmental implications of the current Indian electricity system as well as setting targets for future development. The analysis with the indicator framework provides a deeper understanding of the system, identify and quantify the prevailing sustainability gaps and generate specific targets for interventions. We use this framework to compute national electricity system sustainability index (NESSI) for India. (C) 2014 Elsevier Ltd. All rights reserved.

Impact of river runoff into the ocean on Indian summer monsoon

Rivers of the world discharge about 36000 km 3 of freshwater into the ocean every year. To investigate the impact of river discharge on climate, we have carried out two 100 year simulations using the Community Climate System Model (CCSM3), one including the river runoff into the ocean and the other excluding it. When the river discharge is shut off, global average sea surface temperature (SST) rises by about 0.5 degrees C and the Indian Summer Monsoon Rainfall (ISMR) increases by about 10% of the seasonal total with large increase in the eastern Bay of Bengal and along the west coast of India. In addition, the frequency of occurrence of La Nina-like cooling events in the equatorial Pacific increases and the correlation between ISMR and Pacific SST anomalies become stronger. The teleconnection between the SST anomalies in the Pacific and monsoon is effected via upper tropospheric meridional temperature gradient and the North African-Asian Jet axis.

Performance of WRF-Chem over Indian region: Comparison with measurements

The aerosol mass concentrations over several Indian regions have been simulated using the online chemistry transport model, WRF-Chem, for two distinct seasons of 2011, representing the pre-monsoon (May) and post-monsoon (October) periods during the Indo-US joint experiment `Ganges Valley Aerosol Experiment (GVAX)'. The simulated values were compared with concurrent measurements. It is found that the model systematically underestimates near-surface BC mass concentrations as well as columnar Aerosol Optical Depths (AODs) from the measurements. Examining this in the light of the model-simulated meteorological parameters, we notice the model overestimates both planetary boundary layer height (PBLH) and surface wind speeds, leading to deeper mixing and dispersion and hence lower surface concentrations of aerosols. Shortcoming in simulating rainfall pattern also has an impact through the scavenging effect. It also appears that the columnar AODs are influenced by the unrealistic emission scenarios in the model. Comparison with vertical profiles of BC obtained from aircraft-based measurements also shows a systematic underestimation by the model at all levels. It is seen that concentration of other aerosols, viz., dust and sea-salt are closely linked with meteorological conditions prevailing over the region. Dust is higher during pre-monsoon periods due to the prevalence of north-westerly winds that advect dust from deserts of west Asia into the Indo-Gangetic plain. Winds and rainfall influence sea-salt concentrations. Thus, the unrealistic simulation of wind and rainfall leads to model simulated dust and sea-salt also to deviate from the real values; which together with BC also causes underperformance of the model with regard to columnar AOD. It appears that for better simulations of aerosols over Indian region, the model needs an improvement in the simulation of the meteorology.

A sleep-inducing peptide from the venom of the Indian cone snail Conus araneosus

The marine snail Conus araneosus has unusual significance due to its confined distribution to coastal regions of southeast India and Sri Lanka. Due to its relative scarceness, this species has been poorly studied. In this work, we characterized the venom of C. araneosus to identify new venom peptides. We identified 14 novel compounds. We determined amino acid sequences from chemically-modified and unmodified crude venom using liquid chromatography-electrospray ionization mass spectrometry and matrix assisted laser desorption ionization time-of-flight mass spectrometry. Ten sequences showed six Cys residues arranged in a pattern that is most commonly associated with the M-superfamily of conotoxins. Four other sequences had four Cys residues in a pattern that is most commonly associated with the T-superfamily of conotoxins. The post-translationally modified residue (pyroglutamate) was determined at the N-terminus of two sequences, ar3h and ar3i respectively. In addition, two sequences, ar3g and ar3h were C-terminally amidated. At a dose of 2 nmol, peptide ar3j elicited sleep when injected intraperitoneally into mice. To our knowledge, this is the first report of a peptide from a molluscivorous cone snail with sleep-inducing effects in mice. The novel peptides characterized herein extend the repertoire of unique peptides derived from cone snails and may add value to the therapeutic promise of conotoxins. (C) 2015 Elsevier Ltd. All rights reserved.

An addition to the endemic Indian radiation of Eutropis: Phylogenetic position of Eutropis dissimilis Hallowell (Squamata: Scincidae)

Skinks of the genus Eutropis represent one of the most widespread and speciose lizard groups in tropical Asia. Numerous recent studies have utilized a variety of genes and methods to reconstruct the phylogeny of these lizards, however these studies have not resolved the placement of one of the widely distributed Eutropis Fitzinger, E. dissimilis. We have sequenced a specimen of E. dissimilis from the type locality and our result suggests that it is part of the Indian radiation of Eutropis and not related to African Trachylepis Fitzinger or Southeast Asian Dasia Gray as previously suggested. Furthermore, we report that the sequence of E. dissimilis used in an earlier study of the once cosmopolitan genus `Mabuya' may have been erroneously identified and appears to be a sequence of E. novemcarinata. We also demonstrate that the evolution of a clear lower eyelid, which was considered a synapomorphy for the sister genus Trachylepis, has arisen multiple times in Eutropis.