Search results for "Sequencing"
showing 10 items of 1087 documents
A Novel CCT5 Missense Variant Associated with Early Onset Motor Neuropathy
2020
Diseases associated with acquired or genetic defects in members of the chaperoning system (CS) are increasingly found and have been collectively termed chaperonopathies. Illustrative instances of genetic chaperonopathies involve the genes for chaperonins of Groups I (e.g., Heat shock protein 60, Hsp60) and II (e.g., Chaperonin Containing T-Complex polypeptide 1, CCT). Examples of the former are hypomyelinating leukodystrophy 4 (HLD4 or MitCHAP60) and hereditary spastic paraplegia (SPG13). A distal sensory mutilating neuropathy has been linked to a mutation [p.(His147Arg)] in subunit 5 of the CCT5 gene. Here, we describe a new possibly pathogenic variant [p.(Leu224Val)] of the same subunit b…
Drug connectivity mapping and functional analysis reveal therapeutic small molecules that differentially modulate myelination
2022
Disruption or loss of oligodendrocytes (OLs) and myelin has devastating effects on CNS function and integrity, which occur in diverse neurological disorders, including Multiple Sclerosis (MS), Alzheimer’s disease and neuropsychiatric disorders. Hence, there is a need to develop new therapies that promote oligodendrocyte regeneration and myelin repair. A promising approach is drug repurposing, but most agents have potentially contrasting biological actions depending on the cellular context and their dose-dependent effects on intracellular pathways. Here, we have used a combined systems biology and neurobiological approach to identify compounds that exert positive and negative effects on olig…
Assembly methods for nanopore-based metagenomic sequencing: a comparative study
2019
ABSTRACTBackgroundMetagenomic sequencing has lead to the recovery of previously unexplored microbial genomes. In this sense, short-reads sequencing platforms often result in highly fragmented metagenomes, thus complicating downstream analyses. Third generation sequencing technologies, such as MinION, could lead to more contiguous assemblies due to their ability to generate long reads. Nevertheless, there is a lack of studies evaluating the suitability of the available assembly tools for this new type of data.FindingsWe benchmarked the ability of different short-reads and long-reads tools to assembly two different commercially available mock communities, and observed remarkable differences i…
Immunomic, genomic and transcriptomic characterization of CT26 colorectal carcinoma
2013
Background Tumor models are critical for our understanding of cancer and the development of cancer therapeutics. Here, we present an integrated map of the genome, transcriptome and immunome of an epithelial mouse tumor, the CT26 colon carcinoma cell line. Results We found that Kras is homozygously mutated at p.G12D, Apc and Tp53 are not mutated, and Cdkn2a is homozygously deleted. Proliferation and stem-cell markers, including Top2a, Birc5 (Survivin), Cldn6 and Mki67, are highly expressed while differentiation and top-crypt markers Muc2, Ms4a8a (MS4A8B) and Epcam are not. Myc, Trp53 (tp53), Mdm2, Hif1a, and Nras are highly expressed while Egfr and Flt1 are not. MHC class I but not MHC class…
Case report: Novel compound heterozygosity for pathogenic variants in MED23 in a syndromic patient with postnatal microcephaly
2023
Biallelic loss-of-function variants in MED23 cause a recessive syndromic intellectual disability condition with or without epilepsy (MRT18). Due to the small number of reported individuals, the clinical phenotype of the disorder has not been fully delineated yet, and the spectrum and frequency of neurologic features have not been fully characterized. Here, we report a 5-year-old girl with compound heterozygous for two additional MED23 variants. Besides global developmental delay, axial hypotonia and peripheral increased muscular tone, absent speech, and generalized tonic seizures, which fit well MRT18, the occurrence of postnatal progressive microcephaly has been here documented. A retrospe…
WIDENING THE SCOPE OF NEXT GENERATION SEQUENCING APPLICATIONS IN PEDIATRIC MEDICAL GENETICS
2018
Advances in DNA sequencing technologies through Next Generation Sequencing (NGS) approaches have enabled genome-wide discovery of chromosomal copy-number variants and single-nucleotide changes. NGS technologies are rapidly expanding our ability to identify and better define disease-causing mutations and genotype-phenotype correlation. Pediatric patients may particularly benefit from the introduction of these new technologies. Pediatricians must keep up with all these new skills, both in their residency programs as well as in their continuing medical education programs.
Identification of susceptibility genes in non-syndromic cleft lip with or without cleft palate using whole-exome sequencing
2015
Background Non-syndromic cleft lip with or without cleft palate (NSCL/P) is among the most common congenital malformations. The etiology of NSCL/P remains poorly characterized owing to its complex genetic heterogeneity. The objective of this study was to identify genetic variants that increase susceptibility to NSCL/P. Material and Methods Whole-exome sequencing (WES) was performed in 8 fetuses with NSCL/P in China. Bioinformatics analysis was performed using commercially available software. Variants detected by WES were validated by Sanger sequencing. Results By filtering out synonymous variants in exons, we identified average 8575 nonsynonymous single nucleotide variants (SNVs). We subseq…
Taxas de substituições das Annonaceas: uma perspectiva do modelo códon
2014
The Annonaceae includes cultivated species of economic interest and represents an important source of information for better understanding the evolution of tropical rainforests. In phylogenetic analyses of DNA sequence data that are used to address evolutionary questions, it is imperative to use appropriate statistical models. Annonaceae are cases in point: Two sister clades, the subfamilies Annonoideae and Malmeoideae, contain the majority of Annonaceae species diversity. The Annonoideae generally show a greater degree of sequence divergence compared to the Malmeoideae, resulting in stark differences in branch lengths in phylogenetic trees. Uncertainty in how to interpret and analyse these…
Complete sequencing of Novosphingobium sp. PP1Y reveals a biotechnologically meaningful metabolic pattern.
2014
Background Novosphingobium sp. strain PP1Y is a marine α-proteobacterium adapted to grow at the water/fuel oil interface. It exploits the aromatic fraction of fuel oils as a carbon and energy source. PP1Y is able to grow on a wide range of mono-, poly- and heterocyclic aromatic hydrocarbons. Here, we report the complete functional annotation of the whole Novosphingobium genome. Results PP1Y genome analysis and its comparison with other Sphingomonadal genomes has yielded novel insights into the molecular basis of PP1Y’s phenotypic traits, such as its peculiar ability to encapsulate and degrade the aromatic fraction of fuel oils. In particular, we have identified and dissected several highly …
METAGENOMIC ANALYSIS OF PHYTOPHTHORA DIVERSITY IN NURSERIES OF POTTED ORNAMENTAL SPECIES.
2015
The genetic diversity of Phytophthora was investigated in soil and root samples of potted ornamental and fruit tree plants collected in nurseries located in Apulia and Calabria (Southern Italy) using metagenomic approaches based on Phytophthora genus specific primers. PCR amplicons containing the ITS1 region of the rDNA were sequenced using both a conventional cloning and Sanger sequencing approach and a 454 pyrosequencing protocol. All sequences were accurately analyzed with an appropriate software and used as barcode for species identification utilizing a validated ITS database. The cloning/Sanger sequencing approach enabled the identification of nine different Phytophthora taxa (P. nicot…