シベリア亜寒帯林における樹冠と林床の植生指数

Clinical characteristic of patients with rheumatoid arthritis (RA) and trauma. (DOC 45 kb

Novel mutations in <i>COL4A3</i>, <i>COL4A4</i>, and <i>COL4A5</i> in Chinese patients with Alport Syndrome

<div><p>Alport syndrome (AS) is a clinically and genetically heterogeneous, progressive nephropathy caused by mutations in </p><p><i>COL4A3</i></p>, <p><i>COL4A4</i></p>, and <p><i>COL4A5</i></p>, which encode type IV collagen. The large sizes of these genes and the absence of mutation hot spots have complicated mutational analysis by routine polymerase chain reaction (PCR)-based approaches. Here, in order to design a rapid and effective method for the genetic diagnosis of AS, we developed a strategy by utilizing targeted capture associated with next-generation sequencing (NGS) to analyze <p><i>COL4A3</i></p>, <p><i>COL4A4</i></p>, and <p><i>COL4A5</i></p> simultaneously in 20 AS patients. All the coding exons and flanking sequences of <p><i>COL4A3</i></p>, <p><i>COL4A4</i></p>, and <p><i>COL4A5</i></p> from the probands were captured followed by HiSeq 2500 sequencing. Candidate mutations were validated by classic Sanger sequencing and quantitative (q)PCR. Sixteen patients (16/20, 75%) showed X-linked inheritance, and four patients (4/20, 20%) showed autosomal recessive inheritance. None of the individuals had autosomal-dominant AS. Fifteen novel mutations, 6 known mutations, and 2 novel fragment deletions were detected by targeted capture and NGS. Of these novel mutations, 12, 3, and 2 mutations were detected in <p><i>COL4A5</i></p>, <p><i>COL4A4</i></p>, and <p><i>COL4A3</i></p>, respectively. A comparison of the clinical manifestations caused by different types of mutations in <p><i>COL4A5</i></p> suggested that nonsense mutations and glycine substitution by an acidic amino acid are more severe than the other missense mutations. Pathogenic mutations were detected in 20 patients. These novel mutations can expand the genotypic spectrum of AS. Our results demonstrated that targeted capture and NGS technology are effective in the genetic diagnosis of AS.<p></p></div

Additional file 10: Figure S7. of Long noncoding RNA expression profile in fibroblast-like synoviocytes from patients with rheumatoid arthritis

Co-expression network of the differentially expressed lncRNAs and mRNAs. ENST00000452247 was connected to 18 lncRNAs and 12 mRNAs. Blue nodes represent lncRNAs and yellow nodes represent protein-coding genes. A red line represents positive correlation, and a green line represents negative correlation. (TIF 1529 kb

Additional file 3: Table S3. of Long noncoding RNA expression profile in fibroblast-like synoviocytes from patients with rheumatoid arthritis

Differentially expressed mRNAs in RA FLSs versus normal FLSs. (DOC 174 kb

Additional file 1: Table S1. of Long noncoding RNA expression profile in fibroblast-like synoviocytes from patients with rheumatoid arthritis

Clinical characteristic of patients with rheumatoid arthritis (RA) and trauma. (DOC 45 kb

Mutations detected in <i>COL4A3</i>, <i>COL4A4</i>, and <i>COL4A5</i>.

<p>Mutations detected in <i>COL4A3</i>, <i>COL4A4</i>, and <i>COL4A5</i>.</p

The PCR quantification detected in IID3 and IID10.

<p>A, <b>the PCR quantification results of IID3.</b> The comparison of quantification of exon 29 of <i>COL4A5</i> between patient IID3 and male controls. RQ, real-time quantitative PCR. B, <b>the PCR quantification results of IID10.</b> The comparison of quantification of exon 44 of <i>COL4A5</i> between patient IID10 and male controls. RQ, real-time quantitative PCR.</p

Additional file 6: Figure S3. of Long noncoding RNA expression profile in fibroblast-like synoviocytes from patients with rheumatoid arthritis

Gene ontology (GO) analysis for down-regulated mRNAs. a Biological process (BP) analysis for down-regulated mRNAs. b Cellular component (CC) analysis for down-regulated mRNAs. c Molecular function (MF) analysis for down-regulated mRNAs. (TIF 468 kb