Study of Genomic Copy Number Variation in Equine Health and Disease

This is a study of copy number variations (CNVs) in the horse genome to gain knowledge about the role of CNVs in equine biology, and their contribution to complex diseases and disorders. We constructed a 400K whole-genome tiling array and applied it for the discovery of CNVs in 38 normal horses of 16 diverse breeds, and the Przewalski horse. Altogether, 258 CNV regions (CNVRs) were identified across all autosomes, chrX, and chrUn. The CNVRs comprised 1.3% of the horse genome with chr12 being most enriched. American Miniature Horses had the highest and American Quarter Horses the lowest number of CNVs in relation to Thoroughbred references. The Przewalski horse was similar to native ponies and draft breeds. About 20% of CNVRs were intergenic, while 80% involved 750 annotated genes with molecular functions predominantly in sensory perception, immunity, and reproduction. The findings were integrated with previous CNV studies in the horse to generate a composite genome-wide dataset of 1476 CNVRs. Of these, 301 CNVRs were shared between studies, while 1174 were novel and require further validation. Integrated data revealed that only 41 out of over 400 breeds of the domestic horse have been analyzed for CNVs, whereas this study added 11 new breeds. The composite CNV dataset served as a foundation for the discovery of variants contributing to Recurrent Airway Obstruction (RAO) and XY disorders of sexual development (DSDs), such as cryptorchidism and XY sex reversal. In 16 RAO affected horses 363 CNVRs were identified, of which 31 were novel and not found in healthy horses. A deletion in SPI2 and SERPINA1 was studied in detail because the genes are involved in respiratory diseases in human. In horses with XY DSDs, over 50 novel CNVRs were identified including deletions of functional interest in the pseudoautosomal region and the ATRX gene. A potentially causative homozygous deletion in chr29 disrupting AKR1C genes with functions in sex hormone metabolism was shared between a cryptorchid and two sex reversal horses. The findings effectively improved the knowledge about CNVs in horses, in health and disease, and generated resources for future studies

Dimetallaheteroborane clusters containing group 16 elements: A combined experimental and theoretical study

Recently we described the synthesis and structural characterization of various dimetallaherteroborane clusters, namely nido-[(Cp∗Mo2B4EClxH6−x], 1–3; (1: E = S, x = 0; 2: E = Se, x = 0; 3: E = Te, x = 1). A combined theoretical and experimental study was also performed, which demonstrated that the clusters 1–3 with their open face are excellent precursors for cluster growth reaction. In this investigation process on the reactivity of dimetallaheteroboranes with metal carbonyls, in addition to [(Cp∗Mo)2B4H6EFe(CO)3] (4: E = S, 6: E = Te) reported earlier, reaction of 2 with [ Fe2(CO)9] yielded mixed-metallaselenaborane [(Cp∗Mo)2B4H6SeFe(CO)3], 5 in good yield. The quantum chemical calculation using DFT method has been carried out to probe the bonding, NMR chemical shifts and electronic properties of dimolybdaheteroborane clusters 4–6

i-rDNA: alignment-free algorithm for rapid in silico detection of ribosomal gene fragments from metagenomic sequence data sets

<p>Abstract</p> <p>Background</p> <p>Obtaining accurate estimates of microbial diversity using rDNA profiling is the first step in most metagenomics projects. Consequently, most metagenomic projects spend considerable amounts of time, money and manpower for experimentally cloning, amplifying and sequencing the rDNA content in a metagenomic sample. In the second step, the entire genomic content of the metagenome is extracted, sequenced and analyzed. Since DNA sequences obtained in this second step also contain rDNA fragments, rapid <it>in silico</it> identification of these rDNA fragments would drastically reduce the cost, time and effort of current metagenomic projects by entirely bypassing the experimental steps of primer based rDNA amplification, cloning and sequencing. In this study, we present an algorithm called i-rDNA that can facilitate the rapid detection of 16S rDNA fragments from amongst millions of sequences in metagenomic data sets with high detection sensitivity.</p> <p>Results</p> <p>Performance evaluation with data sets/database variants simulating typical metagenomic scenarios indicates the significantly high detection sensitivity of i-rDNA. Moreover, i-rDNA can process a million sequences in less than an hour on a simple desktop with modest hardware specifications.</p> <p>Conclusions</p> <p>In addition to the speed of execution, high sensitivity and low false positive rate, the utility of the algorithmic approach discussed in this paper is immense given that it would help in bypassing the entire experimental step of primer-based rDNA amplification, cloning and sequencing. Application of this algorithmic approach would thus drastically reduce the cost, time and human efforts invested in all metagenomic projects.</p> <p>Availability</p> <p>A web-server for the i-rDNA algorithm is available at <url>http://metagenomics.atc.tcs.com/i-rDNA/</url></p

ALK-Positive Anaplastic Large Cell Lymphoma Associated With Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) has been rarely reported as a complication of anaplastic large cell lymphoma (ALCL), especially in the adult population. We herein present a case of a young woman who presented with multiorgan failure and disseminated intravascular hemolysis and was later found to have ALCL-associated HLH. We also review the current literature on ALCL-associated HLH in adult patients, with their respective treatments and outcomes. We discuss the challenges associated with the diagnosis of lymphoma in the setting of HLH and multiorgan failure. Further, given its high mortality rates, we highlight the importance of promptly identifying and treating the underlying etiology of HLH

HabiSign: a novel approach for comparison of metagenomes and rapid identification of habitat-specific sequences

<p>Abstract</p> <p>Background</p> <p>One of the primary goals of comparative metagenomic projects is to study the differences in the microbial communities residing in diverse environments. Besides providing valuable insights into the inherent structure of the microbial populations, these studies have potential applications in several important areas of medical research like disease diagnostics, detection of pathogenic contamination and identification of hitherto unknown pathogens. Here we present a novel and rapid, alignment-free method called HabiSign, which utilizes patterns of tetra-nucleotide usage in microbial genomes to bring out the differences in the composition of both diverse and related microbial communities.</p> <p>Results</p> <p>Validation results show that the metagenomic signatures obtained using the HabiSign method are able to accurately cluster metagenomes at biome, phenotypic and species levels, as compared to an average tetranucleotide frequency based approach and the recently published dinucleotide relative abundance based approach. More importantly, the method is able to identify subsets of sequences that are specific to a particular habitat. Apart from this, being alignment-free, the method can rapidly compare and group multiple metagenomic data sets in a short span of time.</p> <p>Conclusions</p> <p>The proposed method is expected to have immense applicability in diverse areas of metagenomic research ranging from disease diagnostics and pathogen detection to bio-prospecting. A web-server for the HabiSign algorithm is available at <url>http://metagenomics.atc.tcs.com/HabiSign/</url>.</p

Concurrent JAK2 V617F Acute Myeloid Leukemia (AML) and Leukemic non-nodal Mantle Cell Lymphoma (LN-MCL): Case study

Introduction/Objective: We report a unique case of concurrently occurring Acute Myeloid Leukemia (AML) and Leukemic non-nodal Mantle Cell Lymphoma (LN-MCL) in an 86-year-old male. To the best of our knowledge, this is the first report of AML occurring in the background of LN-MCL, with no known history of any malignancy or chemotherapy. Methods/Case Report: An 86-year old Caucasian male with unremarkable past medical history presented with pancytopenia, fatigue and generalized weakness. Abdominal CT scan was negative for lymphadenopathy or hepatosplenomegaly. Peripheral blood showed 2% blasts with atypical lymphocytes 89%. Bone marrow aspirate showed 30% myeloblasts expressing CD34, CD117, CD13, CD33, HLA-DR and CD56 (dim) by flow cytometry (FC). Lymphocytes accounted for 40% of bone marrow cellularity. FC identified a population of CD5+ kappa restricted clonal B cells 2%, consistent with a concurrent CD5+ B-lymphoproliferative disorder/lymphoma. The bone marrow biopsy was inadequate for further evaluation of the B- cell lymphoma. Chromosomal analysis revealed a normal male karyotype. FISH analysis was positive for t(11:14) CCND1::IGH rearrangement (in 3.5% of interphase cells) supporting involvement by MCL. Myeloid panel next generation sequencing (51 genes) was positive for JAK2 V617F (VAF, 38%) and ASXL1 P920Tfs*4 (VAF, 22%) variants. Conclusion: Concurrent presence of LN-MCL and AML as seen in our patient in the absence of prior history of malignancy or chemotherapy is rare. Presence of JAK2V617F mutation in de-novo AML is extremely rare (\u3c5%). There is no prior history of myeloproliferative neoplasm (MPN) or CBC data to suggest that this may have progressed from an MPN. While the absence of lymphadenopathy suggests that the CD5+ B-LPD likely represents LN-MCL, it is also likely that the CD5+, IgH/CCND1 rearranged B-cells may represent prior undetected circulating cells without overt LN-MCL development, similar to those reported in otherwise healthy individuals. It is unclear but tempting to speculate that the two co-occurring hematologic malignancies may have a common cell of origin