Clinical and analytical validation of an 82-gene comprehensive genome-profiling panel for identifying and interpreting variants responsible for inherited retinal dystrophies.

Inherited retinal dystrophies comprise a clinically complex and heterogenous group of diseases characterized by visual impairment due to pathogenic variants of over 300 different genes. Accurately identifying the causative gene and associated variant is crucial for the definitive diagnosis and subsequent selection of precise treatments. Consequently, well-validated genetic tests are required in the clinical practice.

Quantitative evaluation of MSI testing using NGS detects the imperceptible microsatellite changed caused by MSH6 deficiency.

Microsatellite instability (MSI) is an effective biomarker for diagnosing Lynch syndrome (LS) and predicting the responsiveness of cancer therapy. MSI testing is conventionally performed by capillary electrophoresis, and MSI status is judged by visual assessment of allele size change. Here, we attempted to develop a quantitative evaluation model of MSI using next-generation sequencing (NGS).

Microarray and whole-exome sequencing analysis of familial Behçet's disease patients.

Behçet's disease (BD), a chronic systemic inflammatory disorder, is characterized by recurrent oral and genital mucous ulcers, uveitis, and skin lesions. We performed DNA microarray analysis of peripheral blood mononuclear cell (PBMC) mRNA from 41 Japanese BD patients and revealed elevated levels of interleukin (IL) 23 receptor (IL23R) mRNA in many BD patients. DNA sequencing around a SNV (Rs12119179) tightly linked to BD revealed an elevated frequency of the C genotype, consistent with a previous report that IL23R is a susceptibility locus for BD.

Next-generation sequencing coupled with a cell-free display technology for high-throughput production of reliable interactome data.

Next-generation sequencing (NGS) has been applied to various kinds of omics studies, resulting in many biological and medical discoveries. However, high-throughput protein-protein interactome datasets derived from detection by sequencing are scarce, because protein-protein interaction analysis requires many cell manipulations to examine the interactions. The low reliability of the high-throughput data is also a problem.

IRView: a database and viewer for protein interacting regions.

Unlabelled: Protein-protein interactions (PPIs) are mediated through specific regions on proteins. Some proteins have two or more protein interacting regions (IRs) and some IRs are competitively used for interactions with different proteins. IRView currently contains data for 3417 IRs in human and mouse proteins.

A comprehensive resource of interacting protein regions for refining human transcription factor networks.

Large-scale data sets of protein-protein interactions (PPIs) are a valuable resource for mapping and analysis of the topological and dynamic features of interactome networks. The currently available large-scale PPI data sets only contain information on interaction partners. The data presented in this study also include the sequences involved in the interactions (i.

Genome-wide screening of dioxin-responsive genes in fetal brain: bioinformatic and experimental approaches.

Many of the effects of dioxins, which are potent environmental pollutants and teratogens, are mediated through the aryl hydrocarbon receptor, also known as the dioxin receptor. The purpose of the present study was to characterize dioxin-responsive genes in a comprehensive manner using two complementary approaches: bioinformatic analysis and microarray analysis. First, we characterized the overall distribution of the cis-regulatory element for the dioxin-responsive element sequence (DRE) 'gcgtg' within putative promoter regions.

Characteristics and clustering of human ribosomal protein genes.

Background: The ribosome is a central player in the translation system, which in mammals consists of four RNA species and 79 ribosomal proteins (RPs). The control mechanisms of gene expression and the functions of RPs are believed to be identical. Most RP genes have common promoters and were therefore assumed to have a unified gene expression control mechanism.

GC-compositional strand bias around transcription start sites in plants and fungi.

Background: A GC-compositional strand bias or GC-skew (=(C-G)/(C+G)), where C and G denote the numbers of cytosine and guanine residues, was recently reported near the transcription start sites (TSS) of Arabidopsis genes. However, it is unclear whether other eukaryotic species have equally prominent GC-skews, and the biological meaning of this trait remains unknown.

Results: Our study confirmed a significant GC-skew (C > G) in the TSS of Oryza sativa (rice) genes.

In silico diagnosis of inherently inhibited gene expression focusing on initial codon combinations.

The translation start site, immediately downstream from the start codon, is a dominant factor for gene expression in Escherichia coli. At present, no method exists to improve the expression level of cloned genes, since it remains difficult to find the best codon combination within the region. We determined the expression parameters that correspond to all sense codons within the first four codons using GFPuv which encodes a derivative of green fluorescent protein.

Computational analysis suggests that alternative first exons are involved in tissue-specific transcription in rice (Oryza sativa).

Motivation: Transcription start site selection and alternative splicing greatly contribute to diversifying gene expression. Recent studies have revealed the existence of alternative first exons, but most have involved mammalian genes, and as yet the regulation of usage of alternative first exons has not been clarified, especially in plants.

Results: We systematically identified putative alternative first exon transcripts in rice, verified the candidates using RT-PCR, and searched for the promoter elements that might regulate the alternative first exons.

Characterization of the splice sites in GT-AG and GC-AG introns in higher eukaryotes using full-length cDNAs.

For the purpose of analyzing the relation between the splice sites and the order of introns, we conducted the following analysis for the GT-AG and GC-AG splice site groups. First, the pre-mRNAs of H. sapiens, M.

Computational comparative analyses of alternative splicing regulation using full-length cDNA of various eukaryotes.

We previously reported a computational approach to infer alternative splicing patterns from Mus musculus full-length cDNA clones and microarray data. Although we predicted a large number of unreported splice variants, the general mechanisms regulating alternative splicing were yet unknown. In the present study, we compared alternative exons and constitutive exons in terms of splice-site strength and frequency of potential regulatory sequences.

A novel feature of microsatellites in plants: a distribution gradient along the direction of transcription.

A computer-based analysis was conducted to assess the characteristics of microsatellites in transcribed regions of rice and Arabidopsis. In addition, two mammals were simultaneously analyzed for a comparative analysis. Our analyses confirmed a novel plant-specific feature in which there is a gradient in microsatellite density along the direction of transcription.

Inferring alternative splicing patterns in mouse from a full-length cDNA library and microarray data.

Although many studies on alternative splicing of specific genes have been reported in the literature, the general mechanism that regulates alternative splicing has not been clearly understood. In this study, we systematically aligned each pair of the 21,076 cDNA sequences of Mus musculus, searched for putative alternative splicing patterns, and constructed a list of potential alternative splicing sites. Two cDNAs are suspected to be alternatively spliced and originating from a common gene if they share most of their region with a high degree of sequence homology, but parts of the sequences are very distinctive or deleted in either cDNA.