Biology subjects

Pandey, N. K.

Publications and source records attributed to Pandey, N. K..

4 recordsLinked to original sources

bioRxiv2024

Constructing a Draft Indian Cattle Pangenome Using Short-Read Sequencing

BackgroundIndian cattle known as desi cattle, renowned for their adaptability to harsh environments and diverse phenotypic traits, represent a valuable genetic resource. While reference genome assemblies have been instrumental in advancing cattle genomics, they often fail to capture the full spectrum of genetic variation present within diverse populations. To address this limitation, we aimed to construct a pangenome for desi cattle by identifying and characterizing Non-Reference Novel Sequences (NRNS). FindingsWe sequenced 68 desi cattle genomes representing seven distinct breeds, generating 48.35 billion short reads. A PanGenome Analysis (PanGA) pipeline was developed in Bash scripts to process these data to identify NRNS missing in the reference genome. A total of 13,065 NRNS with a cumulative length of [~]41 Mbp were identified that exhibited substantial variation across the population. These NRNS were found to be exclusive to Indian desi cattle, matching only 4.1% with the Chinese indicine pangenome. However, a significant proportion ([~]40%) of NRNS displayed ancestral origins within the Bos genus. These sequences were enriched in genic regions, suggesting functional roles, and were associated with quantitative trait loci (QTLs), particularly for milk production. Compared to a single reference genome, the pangenome approach significantly enhanced read mapping accuracy, reduced spurious SNP calls, and facilitated the discovery of novel genetic variants. ConclusionsThis study has successfully established a within-species cattle pangenome specifically focused on desi cattle breeds from India. Our findings highlight the importance of pangenome based analyses for understanding the complex genetic architecture of desi cattle.

genomics↗

bioRxiv2024

Advancing the Indian Cattle Pangenome: Characterizing Non-Reference Sequences in Bos indicus

BackgroundIndia, with the worlds largest cattle population and more than 50 registered breeds of Bos indicus, stands as a vital reservoir of genetic diversity. However, the abundant diversity among Indian cattle breeds highlights the inadequacy of a single reference sequence to represent the entire genomic content of desi cattle. We recognize the need to capture the genomic differences within the Bos indicus population as a whole, and specifically within the dairy cattle subset by identifying non-reference sequences and constructing a pangenome. FindingFive representative genomes of prominent dairy breeds, including Gir, Kankrej, Tharparkar, Sahiwal, and Red Sindhi, were sequenced using 10X Genomics Linked-Read technology. Assemblies generated from these linked-reads ranged from 2.70 Gb to 2.77 Gb,comparable to the Bos indicus Brahman reference genome. A pangenome of Bos indicus cattle was constructed by comparing the newly assembled genomes with the reference using alignment and graph-based methods, revealing 8 Mb and 17.7 Mb of novel sequence respectively. A confident set of 6,844 Non-Reference Unique Insertions (NUIs) spanning 7.57 Mbs was identified through both methods, representing the pangenome of Indian Bos indicus breeds. Comparative analysis with previously published pangenomes unveiled 2.8 Mb (37%) commonality with the Chinese indicine pangenome and only 1% commonality with the Bos taurus pangenome. Among these, 2,312 NUIs - encompassing [~]2 Mb, were commonly found in 98 samples of the 5 breeds and designated as Bos indicus Common Insertions (BICIs) in the population. Furthermore, 926 BICIs were identified within 682 protein-coding genes, 54 long non-coding RNAs (LncRNA), and 18 pseudogenes. These protein-coding genes were enriched for functions such as chemical synaptic transmission, cell junction organization, cell-cell adhesion, and cell morphogenesis. The protein-coding genes were found in various prominent Quantitative Trait Loci (QTL) regions, suggesting potential roles of BICIs in traits related to milk production, reproduction, exterior, health, meat, and carcass. Notably, 63.21% of the bases within the BICIs call set contained interspersed repeats, predominantly LINEs. Additionally,70.28% of BICIs are shared with other domesticated and wild species, highlighting their evolutionary significance. ConclusionThis is the first report unveiling a robust set of NUIs defining the pangenome of Bos indicus breeds of India. The analyses contribute valuable insights into the genomic landscape of desi cattle breeds.

genomics↗

bioRxiv2021

Sonicated fibrils of huntingtin exon-1 preferentially seed neurons and produce toxic assemblies

Huntingtons disease (HD) is a genetically inherited neurodegenerative disorder caused by expansion of a polyglutamine (polyQ) repeats in the exon-1 of huntingtin protein (HTT). The expanded polyQ enhances the amyloidogenic propensity of HTT exon 1 (HTTex1), which forms a heterogeneous mixture of assemblies with some being neurotoxic. While predominantly intracellular, monomeric and aggregated mutant HTT species are also present in the cerebrospinal fluids of HD patients, however, their biological properties are not well understood. To explore the role of extracellular mutant HTT in aggregation and toxicity, we investigated the possible uptake and amplification of recombinant HTTex1 assemblies in cell culture models. We found seeding-competent species in the sonicated HTTex1 fibrils, which preferentially entered human neurons and triggered the amplification of neurotoxic assemblies; astrocytes or epithelial cells were not permissive to the HTTex1 seeding. The aggregation of HTTex1 seeds in neurons depleted endogenous HTT protein with non-pathogenic polyQ repeat, activated apoptotic caspase-3 pathway and induced nuclear fragmentation. Using a panel of novel monoclonal antibodies and genetic mutation, we identified epitopes within the N-terminal 17 amino acids and proline-rich domain of HTTex1 mediating neural seeding. Synaptosome preparations from the brains of HD mice also contained similar neurotoxic seeding-competent mutant HTT species. Our findings suggest that amyloidogenic extracellular mutant HTT assemblies may selectively enter neurons, propagate and produce neurotoxic assemblies.

neuroscience↗

bioRxiv2019

Huntingtin fibrils with different toxicity, structure, and seeding potential can be reversibly interconverted

The first exon of the huntingtin protein (HTTex1) important in Huntingtons Disease (HD) can form cross-{beta} fibrils of varying toxicity. We find that the difference between these fibrils is the degree of entanglement and dynamics of the C-terminal proline-rich domain (PRD) in a mechanism analogous to polyproline film formation. In contrast to fibril strains found for other cross-{beta} fibrils, these HTTex1 fibril types can be reversibly interconverted. This is because the structure of their polyQ fibril core remains unchanged. Further, we find that more toxic fibrils of low entanglement have higher affinities for protein interactors and are more effective seeds for recombinant HTTex1 and HTTex1 in cells. Together these data show how the structure of a framing sequence at the surface of a fibril can modulate seeding, protein-protein interactions, and thereby toxicity in neurodegenerative disease.

biophysics↗