Genetics & Molecular Biology

New discovery: One antibody effective against two viruses !!

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In a recently presented research, it is found that one antibody which was made in response to one hemorrhagic fever virus is effective against other related viruses. This comes as a new acheivement given the fact that scientists are facing significant obstacle while developing broad-spectrum antibody-based therapeutics since viruses even from the same family with same molecular make up and receptor binding sites, will end up having substantial degree of variability. The antibody newly created in-vitro in response to one hemorrhagic fever virus can work against other related viruses whose vaccine is yet not discovered.

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Development of App knock-in mice

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Although numerous pathogenic mutations have been found for Alzheimer’s disease (AD), only a protective mutation has been identified so far in humans. Here we identify possible mutations of protective deletion in the 3′-UTR of the amyloid precursor protein gene (APP) in mice. We use a knock-in mouse model App that carries a sequence of humanized Aβ and three mutations of AD in the endogenous App gene. Modifying the model zygote genome using multiple CRISPR / Cas9 tool combinations produces genetically mosaic animals with various 3′-UTR app deletions. Depending on the efficiency of editing, the 3′-UTR interruption mitigates the development of Aβ pathology through the transcriptional and translational regulation of APP expression. In particular, a knock-in app mouse with a 34 bp deletion in a 52 bp regulator element adjacent to the stop codon shows a substantial reduction in the pathology of Ap. An additional functional characterization of the identified element should provide a deeper understanding of the pathogenic mechanisms of AD.

RNA structure probing with SHAPE-MaP

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RNAs play a key role in many cellular processes. The underlying structure of RNA is an important determinant of how transcripts work, are processed and interact with proteins and ligands that bind to RNA. The analysis of the RNA structure by 2′-hydroxyacacylation selective analyzed by extension of the primer (SHAPE) exploits the reactivity of small electrophilic chemical probes that react with the 2′-hydroxyl group to evaluate the structure of RNA at the resolution of the nucleotide. When coupled with mutational profiling (MaP), in which the modified nucleotides are detected as internal miscoding during reverse transcription and then read by massively parallel sequencing, SHAPE produces quantitative measures for nucleotide of the RNA structure.

Bayesian nonparametric model for discovering isoform

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Most human protein-coding genes can be translated into different particular mRNA isoforms. These elective joining designs support atomic decent variety, and deregulation of isoform articulation assumes a critical part in malady etiology. Be that as it may, isoforms are hard to portray from short-read RNA-seq information since they share indistinguishable subsequences and happen in various frequencies crosswise over tissues and tests. Scientists have demonstrated BIISQ, a Bayesian nonparametric model for isoform revelation and individual particular measurement from short-read RNA-seq information. BIISQ does not require isoform reference successions but rather assesses an isoform index shared crosswise over examples.

Mutation of IPO13 can cause coloboma, microphthalmia, and cataract

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Ocular coloboma is a formative auxiliary deformity of the eye that frequently happens as perplexing ocular anomalies. Nonetheless, its genetic etiology remains to a great extent unexplored. Scientists report the distinguishing proof of mutation (c.331C>T, p.R111C) in the IPO13 gene in a consanguineous family with visual coloboma, microphthalmia, and cataract by a whole-exome sequencing and homozygosity mapping. IPO13 encodes an importin-B family protein and has been ended up being related with the pathogenesis of coloboma and microphthalmia. They found that Ipo13 was communicated in the cornea, sclera, focal point, and retina in mice. Moreover, the mRNA articulation level of Ipo13 diminished fundamentally in the patient contrasted and its appearance in a solid person. Morpholino-oligonucleotide-instigated knockdown of ipo13 in zebrafish caused dosage subordinate microphthalmia and coloboma, which is exceptionally like the ocular phenotypes in the patient.


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Alternative splicing is mediated by human multi-exonic coding genes

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Alternative splicing (AS) is a pre-mRNA process for the most part controlled by post-transcriptional regulation including 90% of human multi-exonic coding genes in an assortment of tissues and cell types. Numerous investigations have featured the key part of AS in regulating cellular development and differentiation, and distorted AS events prompt disease states, for example, muscular dystrophies and cancer. Accumulating evidence further supports a new paradigm that AS is a co-transcriptional splicing process mutually coordinated by transcription and splicing. Late examinations additionally delineate that splicing is likewise directed by epigenetic regulators, including chromatin structure, histone modifications, and CTCF. Dysregulation of some epigenetic segments may alter the splicing process, resulting different kinds of human diseases. For example, a current report revealed that a transformation of the histone methyl transferase SEDT2 modifies AS of a few key WNT signaling regulatory genes, resulting colorectal cancer.

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