Biology subjects

Kohli, S.

Publications and source records attributed to Kohli, S..

21 records · Page 2Linked to original sources

bioRxiv2019

A comparative analysis of histone methyltransferases and demethylases in insect genome: A meta-analysis

BackgroundThe epigenetic regulation through post-translational modification of histones, especially methylation is well conserved, while DNA methylation is variable, being very low or absent in Drosophila melanogaster. Though there are several insect genomes sequenced, an analysis with a focus on their epigenetic repertoire is limited. We have compared the histone methyltransferases and the demethylases in the genome of Drosophila melanogaster, Aedes aegypti (Diptera), the pea aphid Acyrthosiphon pisum, the triatomid bug Rhodnius prolixus (Hemiptera), the honeybee Apis mellifera (Hymenoptera), the silkworm Bombyx mori (Lepidoptera) and the red flour beetle Tribolium castaneum (Coleoptera).\n\nResultsWe identified 38 clusters consisting of arginine, lysine methyltransferases and demethylases using OrthoFinder. To eliminate false positives, we designed a method based on identifying highly conserved domain within each class designated as the high priority domain. Out of the 9 arginine methyltransferases, Art2, Art6 and Art9 are identified in D.melanogaster only. We observe copy number variation between the genomes; A.pisum has nine copies of eggless gene (H3K9me3 methyltransferase), which can be correlated with the switch between parthenogenesis and sexual reproduction. Other than the high-priority domains, these proteins contain shared and unique domains that can mediate protein-protein interaction. Phylogenetic analysis indicates that the there is a broad conservation within the members of a class while duplication and divergence is observed in LSD1.\n\nConclusionThis meta-analysis provides a method for reliable identification of epigenetic modifiers of histones in newly sequenced insect genomes. Similar approach can be taken for other classes of genes.

genomics↗

bioRxiv2018

Downregulation of the central noradrenergic system by Toxoplasma gondii infection

The parasitic protozoan Toxoplasma gondii becomes encysted in brain and muscle tissue during chronic infection, a stage that was previously thought to be dormant but has been found to be active and associated with physiological effects in the host. Dysregulation of catecholamines in the CNS has previously been observed in chronically-infected animals. In the study described here, the noradrenergic system was suppressed with decreased levels of norepinephrine in brains of infected animals and in infected neuronal cells in vitro. Expression of dopamine {beta}-hydroxylase (DBH), essential for synthesis of norepinephrine from dopamine, was the most differentially-expressed gene in infections in vitro and was down-regulated in infected brain tissue, particularly in the prefrontal cortex and dorsal locus coeruleus/pons region. The down-regulated DBH expression in infected rat catecholaminergic and human neuronal cells corresponded with decreased norepinephrine and increased dopamine. As the DBH suppression was observed in vitro, this effect is not caused by neuroinflammation. Silencing of DBH expression was specific for T. gondii infection and was not observed with CMV infection. The noradrenergic-linked behaviors of sociability and arousal were altered in chronically-infected animals, with a high correlation between DBH expression and infection intensity. These findings together provide a plausible mechanism to explain prior discrepancies in changes to CNS neurotransmitters levels with infection. The suppression of norepinephrine synthesis observed here may, in part, explain behavioural effects of infection, associations with mental illness, and neurological consequences of infection such as the loss of coordination and motor impairments associated with human toxoplasmosis.

microbiology↗

bioRxiv2017

Genetic Identification Of A Common Collagen Disease In Puerto Ricans Via Identity-By-Descent Mapping In A Health System

Achieving confidence in the causality of a disease locus is a complex task that often requires supporting data from both statistical genetics and clinical genomics. Here we describe a combined approach to identify and characterize a genetic disorder that leverages distantly related patients in a health system and population-scale mapping. We utilize genomic data to uncover components of distant pedigrees, in the absence of recorded pedigree information, in the multi-ethnic BioMe biobank in New York City. By linking to medical records, we discover a locus associated with genetic relatedness that also underlies extreme short stature. We link the gene, COL27A1, with a little-known genetic disease, previously thought to be rare and recessive. We demonstrate that disease manifests in both heterozygotes and homozygotes, indicating a common collagen disorder impacting up to 2% of individuals of Puerto Rican ancestry, leading to a better understanding of the continuum of complex and Mendelian disease.

genomics↗