Cardiac conduction disease (CCD), which causes altered electrical impulse propagation in the heart, is a life-threatening condition with high morbidity and mortality. It exhibits genetic and clinical heterogeneity with diverse pathomechanisms, but in most cases, it disrupts the synchronous activity of impulse-generating nodes and impulse-conduction underlying the normal heartbeat. In this study, we investigated a consanguineous Pakistani family comprised of four patients with CCD. We applied whole exome sequencing (WES) and co-segregation analysis, which identified a novel homozygous missense mutation (c.1531T>C;(p.Ser511Pro)) in the highly conserved kinase domain of the cardiac troponin I-interacting kinase (TNNI3K) encoding gene. The behaviors of mutant and native TNNI3K were compared by performing all-atom long-term molecular dynamics simulations, which revealed changes at the protein surface and in the hydrogen bond network. Furthermore, intra and intermolecular interaction analyses revealed that p.Ser511Pro causes structural variation in the ATP-binding pocket and the homodimer interface. These findings suggest p.Ser511Pro to be a pathogenic variant. Our study provides insights into how the variant perturbs the TNNI3K structure-function relationship, leading to a disease state. This is the first report of a recessive mutation in TNNI3K and the first mutation in this gene identified in the Pakistani population.

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Cotton dusky bug (Oxycarenus spp.) mostly attack on cash crops such as Gossypium, Cola and Hibiscus which affect the national economy therefore sustainable pest management is needed. Cytochrome c oxidase I (COI) gene is utilized as marker gene for DNA barcoding, genetic and ecological study of insects. In present study insect (cotton dusky bug) samples were collected from cotton fields in Faisalabad. COI gene was amplified from genomic DNA of bug and cloned into pTZ57R/T vector (Fermentas). The clone was sent to Macrogen (South Korea) for Sanger sequencing. The phylogenetic analysis and pairwise multiple sequence alignment showed that our cotton dusky bug grouped with two species of Oxycarenus genus and highest sequence identity was 91.1% with Oxycarenus hylinipennis. This is the first report of genetic barcode of Oxycarenus hylinipennis from cotton from Pakistan.