S. Santhosh

Sequencing and analysis of a South Asian-Indian personal genome

BackgroundWith over 1.3 billion people, India is estimated to contain three times more genetic diversity than does Europe. Next-generation sequencing technologies have facilitated the understanding of diversity by enabling whole genome sequencing at greater speed and lower cost. While genomes from people of European and Asian descent have been sequenced, only recently has a single male genome from the Indian subcontinent been published at sufficient depth and coverage. In this study we have sequenced and analyzed the genome of a South Asian Indian female (SAIF) from the Indian state of Kerala.ResultsWe identified over 3.4 million SNPs in this genome including over 89,873 private variations. Comparison of the SAIF genome with several published personal genomes revealed that this individual shared ~50% of the SNPs with each of these genomes. Analysis of the SAIF mitochondrial genome showed that it was closely related to the U1 haplogroup which has been previously observed in Kerala. We assessed the SAIF genome for SNPs with health and disease consequences and found that the individual was at a higher risk for multiple sclerosis and a few other diseases. In analyzing SNPs that modulate drug response, we found a variation that predicts a favorable response to metformin, a drug used to treat diabetes. SNPs predictive of adverse reaction to warfarin indicated that the SAIF individual is not at risk for bleeding if treated with typical doses of warfarin. In addition, we report the presence of several additional SNPs of medical relevance.ConclusionsThis is the first study to report the complete whole genome sequence of a female from the state of Kerala in India. The availability of this complete genome and variants will further aid studies aimed at understanding genetic diversity, identifying clinically relevant changes and assessing disease burden in the Indian population.

Biosystematics and biogeography of Oriental Chalcidoidea (Hymenoptera) Associated with plant galls

Abstract Chalcidoid wasps have exquisite life histories and diverse host relationships. They are believed to have originated in the upper Jurassic period. Among the chalcidoids it is not always easy to separate the obligatory gall inhabitants and those which have a discrete association with the galls. The following three categories of chalcidoids are treated in the present article (i) gall inducers (ii) gall inquilines and (iii) parasitoids attacking the gall inducers and gall inquilines. Gall-inducing chalcidoids mostly belong to Agaonidae, Eulophidae, Eurytomidae, Pteromalidae, Tanaostigmatidae, and Torymidae. The families of Chalcidoidea associated with plant galls in widely varying degrees of dependence are Aphelinidae, Encyrtidae, Trichogrammatidae, Eupelmidae, Mymaridae, Ormyridae, and Chalcididae. Several hypotheses explain the phylogeny of Chalcidoidea. Morphological features tend to support the monophyletic origin of Chalcidoidea. However, no hypothesis is acceptable totally to a chalcidologist, since a comprehensive knowledge on the distribution of the character states throughout the superfamily is lacking. Gall induction arose more then once in the six families referred above. The biogeography of gall-associated Chalcidoidea is related to the distribution of their respective host plants. The Oriental chalcidoids are not isolated from the nearby Asiatic and Middle-eastern countries. Even the Palearctic and Ethiopian elements are quite frequently met with in the Oriental region.

Prevalence of genetic variants associated with cardiovascular disease risk and drug response in the Southern Indian population of Kerala.

BACKGROUND AND AIM: This study reports the prevalence of five clinically significant variants associated with increased risk of cardiovascular disorders, and variable responses of individuals to commonly prescribed cardiovascular drugs in a South Indian population from the state of Kerala. MATERIALS AND METHODS: Genomic DNA isolated from 100 out-patient samples from Kerala were sequenced to examine the frequency of clinically relevant polymorphisms in the genes MYBPC3 (cardiomyopathy), SLCO1B1 (statin-induced myopathy), CYP2C9, VKORC1 (response to warfarin) and CYP2C19 (response to clopidogrel). RESULTS: Our analyses revealed the frequency of a 25 bp deletion variant of MYBPC3 associated with risk of cardiomyopathy was 7%, and the SLCO1B1 “C” allele associated with risk for statin-induced myopathy was 15% in this sample group. Among the other variants associated with dose-induced toxicity of warfarin, VKORC1 (c.1639G>A), was detected at 22%, while CYP2C9*3 and CYP2C9*2 alleles were present at a frequency of 15% and 3% respectively. Significantly, the tested sample population showed high prevalence (66%) of CYP2C19*2 variant, which determines response to clopidogrel therapy. CONCLUSIONS: We have identified that certain variants associated with cardiovascular disease and related drug response in the five genes, especially those in VKORC1, CYP2C19 and MYBPC3, are highly prevalent in the Kerala population, with almost 2 times higher prevalence of CYP2C19*2 variant compared with other regions in the country. Since the variants chosen in this study have relevance in disease phenotype and/or drug response, and are detected at a higher frequency, this study is likely to encourage clinicians to perform genetic testing before prescribing therapy.

Evolution of targeted therapies in cancer: opportunities and challenges in the clinic

Targeted therapies have changed the course of cancer treatment in recent years. By reducing toxicity and improving outcome, these new generations of precision medicines have extended patient lives beyond what could be achieved by the use of nontargeted therapies. In the last 2 years, several new molecular entities targeting signaling proteins and immune pathways have gone through successful clinical development resulting in their approval. These new targeted therapies require patient selection and the discovery of biomarkers of response. This review discusses the evolution of targeted therapies in cancer and challenges in translating the concepts into clinical practice.

A revision of Neotrichoporoides Girault (Hymenoptera: Eulophidae) from India

Abstract The Indian species of the eulophid genus Neotrichoporoides Girault are revised. The genus is represented by ten species. These are Neotrichoporoides viridimaculatus (Fullaway), N. beonus Narendran, sp. nov., N. crinius Narendran, sp. nov., N. mediterraneus Graham, N. delhiensis (Shafee, Fatma & Kishore), N. tonimus Narendran, sp. nov., N. stom Narendran & Jilcy, sp. nov., N. curiosus Narendran & Girish, sp. nov., N. galia Narendran & Santhosh, sp. nov., and N. nyemitawus (Rohwer). A key to the Indian species is provided.

A New Species of Eulophidae (Hymenoptera: Chalcidoidea) from Kerala, India

A new species,Tamarixia sheebae, is described and illustrated.Tamarixia sheebae differs fromT. bicolor Mercet andT. radiata Waterston in having the apex of gaster tilted upwards. It emerged from leaf galls ofTerminalia arjuna (Roxb.) Wright & Arn. (Combretaceae), a tree with many medicinal properties in addition to its timber value.

The complete mitochondrial genome of Indian cattle (Bos indicus)

Abstract India has 40 distinct zebuine cattle breeds with different adaptability and production traits. In the present study, we report the complete mitochondrial genome sequence of Indian cattle for the first time. The mitogenome contains 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes and a control region (D-loop region). The phylogenetic analysis showed close genetic relationship among the Indian cattle breeds studied, where as, distinct genetic differences were observed between Bos indicus and Bos taurus cattle. Our results will expand genomic information for further studies on evolution, domestication and conservation of indigenous cattle breeds in India.

Comprehensive genomic analysis identifies pathogenic variants in maturity-onset diabetes of the young (MODY) patients in South India

BackgroundMaturity-onset diabetes of the young (MODY) is an early-onset, autosomal dominant form of non-insulin dependent diabetes. Genetic diagnosis of MODY can transform patient management. Earlier data on the genetic predisposition to MODY have come primarily from familial studies in populations of European origin.MethodsIn this study, we carried out a comprehensive genomic analysis of 289 individuals from India that included 152 clinically diagnosed MODY cases to identify variants in known MODY genes. Further, we have analyzed exome data to identify putative MODY relevant variants in genes previously not implicated in MODY. Functional validation of MODY relevant variants was also performed.ResultsWe found MODY 3 (HNF1A; 7.2%) to be most frequently mutated followed by MODY 12 (ABCC8; 3.3%). They together account for ~ 11% of the cases. In addition to known MODY genes, we report the identification of variants in RFX6, WFS1, AKT2, NKX6–1 that may contribute to development of MODY. Functional assessment of the NKX6–1 variants showed that they are functionally impaired.ConclusionsOur findings showed HNF1A and ABCC8 to be the most frequently mutated MODY genes in south India. Further we provide evidence for additional MODY relevant genes, such as NKX6–1, and these require further validation.

Comprehensive analysis of single molecule sequencing-derived complete genome and whole transcriptome of Hyposidra talaca nuclear polyhedrosis virus

We sequenced the Hyposidra talaca NPV (HytaNPV) double stranded circular DNA genome using PacBio single molecule sequencing technology. We found that the HytaNPV genome is 139,089 bp long with a GC content of 39.6%. It encodes 141 open reading frames (ORFs) including the 37 baculovirus core genes, 25 genes conserved among lepidopteran baculoviruses, 72 genes known in baculovirus, and 7 genes unique to the HytaNPV genome. It is a group II alphabaculovirus that codes for the F protein and lacks the gp64 gene found in group I alphabaculovirus viruses. Using RNA-seq, we confirmed the expression of the ORFs identified in the HytaNPV genome. Phylogenetic analysis showed HytaNPV to be closest to BusuNPV, SujuNPV and EcobNPV that infect other tea pests, Buzura suppressaria, Sucra jujuba, and Ectropis oblique, respectively. We identified repeat elements and a conserved non-coding baculovirus element in the genome. Analysis of the putative promoter sequences identified motif consistent with the temporal expression of the genes observed in the RNA-seq data.

Author Correction: Comprehensive analysis of single molecule sequencing-derived complete genome and whole transcriptome of Hyposidra talaca nuclear polyhedrosis virus

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