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Venigalla, S.

Publications and source records attributed to Venigalla, S..

2 recordsLinked to original sources

The Genome of the American Dog Tick (Dermacentor variabilis)

The American dog tick (Dermacentor variabilis) is a vector of zoonotic pathogens in North America that poses emerging threats to public health. Despite its medical importance, genomic resources for D. variabilis remain scarce. Leveraging long-read nanopore sequencing, we generated a high-quality genome assembly for D. variabilis with a final size of 2.15 Gb, an N50 of 445 kb, and a BUSCO completeness score of 95.2%. Comparative BUSCO analyses revealed fewer duplicate genes in our assembly than in other Dermacentor genomes, indicating improved haplotype resolution. The mitochondrial genome, assembled as a single circular contig, clustered monophyletically with D. variabilis isolates from the Upper Midwest, corroborating regional phylogenetic relationships. Repetitive element analysis identified 61% of the genome as repetitive, dominated by LINEs and LTR elements, with 24% remaining unclassified, underscoring the need for further exploration of transposable elements in tick genomes. Gene annotation predicted 21,722 putative genes, achieving a protein BUSCO completeness of 80.88%. Additionally, genome-wide methylation analysis revealed 9.9% global 5mC methylation, providing the first insights into epigenetic modifications in D. variabilis. Further, nanopore sequencing detected Rickettsia montanensis and a non-pathogenic Francisella-like endosymbiont. These findings expand our understanding of tick genomics and epigenetics, offering valuable resources for comparative studies and evolutionary analyses.

genomics↗

Effects of HMGCR deficiency on skeletal muscle development

Pathogenic variants in HMGCR were recently linked to a limb-girdle muscular dystrophy (LGMD) phenotype. The protein product HMG CoA reductase (HMGCR) catalyzes a key component of the cholesterol synthesis pathway. The two other muscle diseases associated with HMGCR, statin-associated myopathy (SAM) and autoimmune anti-HMGCR myopathy, are not inherited in a Mendelian pattern. The mechanism linking pathogenic variants in HMGCR with skeletal muscle dysfunction is unclear. We knocked down Hmgcr in mouse skeletal myoblasts, knocked down hmgcr in Drosophila, and expressed three pathogenic HMGCR variants (c.1327C>T, p.Arg443Trp; c.1522_1524delTCT, p.Ser508del; and c.1621G>A, p.Ala541Thr) in Hmgcr knockdown mouse myoblasts. Hmgcr deficiency was associated with decreased proliferation, increased apoptosis, and impaired myotube fusion. Transcriptome sequencing of Hmgcr knockdown versus control myoblasts revealed differential expression involving mitochondrial function, with corresponding differences in cellular oxygen consumption rates. Both ubiquitous and muscle-specific knockdown of hmgcr in Drosophila led to lethality. Overexpression of reference HMGCR cDNA rescued myotube fusion in knockdown cells, whereas overexpression of the pathogenic variants of HMGCR cDNA did not. These results suggest that the three HMGCR-related muscle diseases share disease mechanisms related to skeletal muscle development.

developmental biology↗