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Actively retrotransposing primate-specific Alu repeats display insertion-deletion (InDel) polymorphism through their insertion at new loci. In the global datasets, Indian populations remain under-represented and so do their Alu InDels. Here, we report the genomic landscape of Alu InDels from the recently released 1021 Indian Genomes (IndiGen) (available at https://clingen.igib.res.in/indigen). We identified 9239 polymorphic Alu insertions that include private (3831), rare (3974) and common (1434) insertions with an average of 770 insertions per individual. We achieved an 89% PCR validation of the predicted genotypes in 94 samples tested. About 60% of identified InDels are unique to IndiGen when compared to other global datasets; 23% of sites were shared with both SGDP and HGSVC; among these, 58% (1289 sites) were common polymorphisms in IndiGen. The insertions not only show a bias for genic regions, with a preference for introns but also for the associated genes showing enrichment for processes like cell morphogenesis and neurogenesis ( P -value < 0.05). Approximately, 60% of InDels mapped to genes present in the OMIM database. Finally, we show that 558 InDels can serve as ancestry informative markers to segregate global populations. This study provides a valuable resource for baseline Alu InDels that would be useful in population genomics., (The Author(s) 2022. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)

Background: Smooth muscle cells (SMCs) transition into a number of different phenotypes during atherosclerosis, including those that resemble fibroblasts and chondrocytes, and make up the majority of cells in the atherosclerotic plaque. To better understand the epigenetic and transcriptional mechanisms that mediate these cell state changes, and how they relate to risk for coronary artery disease (CAD), we have investigated the causality and function of transcription factors at genome-wide associated loci., Methods: We used CRISPR-Cas 9 genome and epigenome editing to identify the causal gene and cells for a complex CAD genome-wide association study signal at 2q22.3. Single-cell epigenetic and transcriptomic profiling in murine models and human coronary artery smooth muscle cells were used to understand the cellular and molecular mechanism by which this CAD risk gene exerts its function., Results: CRISPR-Cas 9 genome and epigenome editing showed that the complex CAD genetic signals within a genomic region at 2q22.3 lie within smooth muscle long-distance enhancers for ZEB2 , a transcription factor extensively studied in the context of epithelial mesenchymal transition in development of cancer. Zeb2 regulates SMC phenotypic transition through chromatin remodeling that obviates accessibility and disrupts both Notch and transforming growth factor β signaling, thus altering the epigenetic trajectory of SMC transitions. SMC-specific loss of Zeb2 resulted in an inability of transitioning SMCs to turn off contractile programing and take on a fibroblast-like phenotype, but accelerated the formation of chondromyocytes, mirroring features of high-risk atherosclerotic plaques in human coronary arteries., Conclusions: These studies identify ZEB2 as a new CAD genome-wide association study gene that affects features of plaque vulnerability through direct effects on the epigenome, providing a new therapeutic approach to target vascular disease.

Background: Autoinflammatory disorders are the group of inherited inflammatory disorders caused due to the genetic defect in the genes that regulates innate immune systems. These have been clinically characterized based on the duration and occurrence of unprovoked fever, skin rash, and patient's ancestry. There are several autoinflammatory disorders that are found to be prevalent in a specific population and whose disease genetic epidemiology within the population has been well understood. However, India has a limited number of genetic studies reported for autoinflammatory disorders till date. The whole genome sequencing and analysis of 1029 Indian individuals performed under the IndiGen project persuaded us to perform the genetic epidemiology of the autoinflammatory disorders in India., Results: We have systematically annotated the genetic variants of 56 genes implicated in autoinflammatory disorder. These genetic variants were reclassified into five categories (i.e., pathogenic, likely pathogenic, benign, likely benign, and variant of uncertain significance (VUS)) according to the American College of Medical Genetics and Association of Molecular pathology (ACMG-AMP) guidelines. Our analysis revealed 20 pathogenic and likely pathogenic variants with significant differences in the allele frequency compared with the global population. We also found six causal founder variants in the IndiGen dataset belonging to different ancestry. We have performed haplotype prediction analysis for founder mutations haplotype that reveals the admixture of the South Asian population with other populations. The cumulative carrier frequency of the autoinflammatory disorder in India was found to be 3.5% which is much higher than reported., Conclusion: With such frequency in the Indian population, there is a great need for awareness among clinicians as well as the general public regarding the autoinflammatory disorder. To the best of our knowledge, this is the first and most comprehensive population scale genetic epidemiological study being reported from India., (© 2021. The Author(s).)

With the advent of next-generation sequencing, large-scale initiatives for mining whole genomes and exomes have been employed to better understand global or population-level genetic architecture. India encompasses more than 17% of the world population with extensive genetic diversity, but is under-represented in the global sequencing datasets. This gave us the impetus to perform and analyze the whole genome sequencing of 1029 healthy Indian individuals under the pilot phase of the 'IndiGen' program. We generated a compendium of 55,898,122 single allelic genetic variants from geographically distinct Indian genomes and calculated the allele frequency, allele count, allele number, along with the number of heterozygous or homozygous individuals. In the present study, these variants were systematically annotated using publicly available population databases and can be accessed through a browsable online database named as 'IndiGenomes' http://clingen.igib.res.in/indigen/. The IndiGenomes database will help clinicians and researchers in exploring the genetic component underlying medical conditions. Till date, this is the most comprehensive genetic variant resource for the Indian population and is made freely available for academic utility. The resource has also been accessed extensively by the worldwide community since it's launch., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Human migration and community specific cultural practices have contributed to founder events and enrichment of the variants associated with genetic diseases. While many founder events in isolated populations have remained uncharacterized, the application of genomics in clinical settings as well as for population scale studies in the recent years have provided an unprecedented push towards identification of founder variants associated with human health and disease. The discovery and characterization of founder variants could have far reaching implications not only in understanding the history or genealogy of the disease, but also in implementing evidence based policies and genetic testing frameworks. This further enables precise diagnosis and prevention in an attempt towards precision medicine. This review provides an overview of founder variants along with methods and resources cataloging them. We have also discussed the public health implications and examples of prevalent disease associated founder variants in specific populations., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Competing Interests: There are no conflicts of interest.

Introduction: WHO endorsed Xpert MTB/RIF assay has proven to be rapid with results obtained within 2h. The evidence base regarding the use of Xpert MTB/RIF in pulmonary TB is strong. Relatively few performance data have been published to date on detection of Mycobacterium tuberculosis in aspirated pus specimens from abscesses., Objectives: The aim of the study was to determine the sensitivity and specificity of Xpert MTB/RIF assay for the detection of M. tuberculosis and rifampicin resistance in aspirated pus specimens using culture on Lowenstein Jensen (LJ) medium and economic variant of proportion method (PM) for drug susceptibility testing (DST) as the reference standard., Results: Xpert MTB/RIF assay in comparison to conventional reference method showed sensitivity and specificity of 76.19% and 68.75% for detection of M. tuberculosis and 71.4% and 100% for detection of rifampicin resistance respectively., Conclusion: The simplicity, sensitivity, speed and automation makes this assay a very promising diagnostic test for detection of M. tuberculosis and rifampicin resistance in aspirated pus specimens., (Copyright © 2018 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Circular RNAs (circRNAs) are transcript isoforms generated by back-splicing of exons and circularisation of the transcript. Recent genome-wide maps created for circular RNAs in humans and other model organisms have motivated us to explore the repertoire of circular RNAs in zebrafish, a popular model organism. We generated RNA-seq data for five major zebrafish tissues - Blood, Brain, Heart, Gills and Muscle. The repertoire RNA sequence reads left over after reference mapping to linear transcripts were used to identify unique back-spliced exons utilizing a split-mapping algorithm. Our analysis revealed 3,428 novel circRNAs in zebrafish. Further in-depth analysis suggested that majority of the circRNAs were derived from previously well-annotated protein-coding and long noncoding RNA gene loci. In addition, many of the circular RNAs showed extensive tissue specificity. We independently validated a subset of circRNAs using polymerase chain reaction (PCR) and divergent set of primers. Expression analysis using quantitative real time PCR recapitulate selected tissue specificity in the candidates studied. This study provides a comprehensive genome-wide map of circular RNAs in zebrafish tissues.

Circular RNAs are an emerging class of transcript isoforms created by unique back splicing of exons to form a closed covalent circular structure. While initially considered as product of aberrant splicing, recent evidence suggests unique functions and conservation across evolution. While circular RNAs could be largely attributed to have little or no potential to encode for proteins, recent evidence points to at least a small subset of circular RNAs which encode for peptides. Circular RNAs are also increasingly shown to be biomarkers for a number of diseases including neurological disorders and cancer. The advent of deep sequencing has enabled large-scale identification of circular RNAs in human and other genomes. A number of computational approaches have come up in recent years to query circular RNAs on a genome-wide scale from RNA-seq data. In this chapter, we describe the application and methodology of identifying circular RNAs using three popular computational tools: FindCirc, Segemehl, and CIRI along with approaches for experimental validation of the unique splice junctions.

Zoonotic infections are increasingly becoming public health menaces and are usually transmitted to humans due to unsuitable environmental conditions. One of them is hepatic capillariasis, caused by the parasite Capillaria hepatica, primarily a disease of rodents, with hepatic manifestations in humans. Although its prevalence is very low, it can cause significant morbidity and mortality, with cases reported from all over the world. The main infective form for humans is the embryonated egg of the parasite, which hatches in the intestine and ultimately colonize the liver. The larvae mature and reproduce, and eventually form embryonated eggs, which cause chronic focal inflammation and septal hepatic fibrosis. Clinical presentation mainly consists of fever, abdominal pain, hepatomegaly and eosinophilia. Spurious infection with unembryonated eggs cause gastrointestinal symptoms. Diagnostic modalities include liver biopsy, ultrasonography, CT scan, immunological tests like ELISA and IIFT. The infection can be treated mainly with a combination of benzimidazoles like thiabendazole, mebendazole and albendazole; with corticosteroids. The study emphasizes the need for hepatic capillariasis to be considered as a differential diagnosis in cases of suspected hepatitis, leptospirosis, abdominal lymphadenopathy or other hepatic or parasitic infections prevalent in the region concerned; and meticulously assess the cases to facilitate early diagnosis and prompt treatment, thus reducing the distress faced by patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

In view of the escalating need for autologous cell-based therapy for treatment of liver diseases, a novel candidate has been explored in the present study. The monocytes isolated from hepatitis B surface antigen (HBsAg) nucleic acid test (NAT)-positive (HNP) blood were differentiated to hepatocyte-like cells (NeoHep) in vitro by a two-step culture procedure. The excess neutrophils present in HNP blood were removed before setting up the culture. In the first step of culture, apoptotic cells were depleted and genes involved in hypoxia were induced, which was followed by the upregulation of genes involved in the c-MET signaling pathway in the second step. The NeoHep were void of hepatitis B virus and showed expression of albumin, connexin 32, hepatocyte nuclear factor 4-α, and functions such as albumin secretion and cytochrome P450 enzyme-mediated detoxification of xenobiotics. The engraftment of NeoHep derived from HBsAg-NAT-positive blood monocytes in partially hepatectomized NOD.CB17-Prkdc scid /J mice liver and the subsequent secretion of human albumin and clotting factor VII activity in serum make NeoHep a promising candidate for cell-based therapy. Stem Cells Translational Medicine 2017;6:174-186., (© 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)