Additional file 1: of Publication of nuclear magnetic resonance experimental data with semantic web technology and the application thereof to biomedical research of proteins

Further detail of the BMRB/XML, BMRB/RDF and web services including SPARQL endpoint. Complete results of the SPARQL query (Fig. 2a) and many other SPARQL query examples are also available. (PDF 6814 kb

Additive effects of genetic variants associated with intraocular pressure in primary open-angle glaucoma

<div><p>To investigate the association between the additive effects of genetic variants associated with intraocular pressure (IOP) and IOP, vertical cup-to-disc ratio (VCDR), and high tension glaucoma (HTG) or normal tension glaucoma (NTG) as phenotypic features of primary open-angle glaucoma (POAG), and to evaluate the clinical usefulness of the additive effects of IOP-related genetic variants for predicting IOP elevation, Japanese patients with HTG (n = 255) and NTG (n = 261) and 246 control subjects were genotyped for nine IOP-related genetic variants near <i>CAV2</i>, <i>GAS7</i>, <i>GLCCI1/ICA1</i>, <i>ABCA1</i>, <i>ARHGEF12</i>, <i>FAM125B</i>, <i>FNDC3B</i>, <i>ABO</i>, and <i>PTPRJ/AGBL2</i>. The total number of risk alleles of these genetic variants was calculated for each participant as a genetic risk score (GRS), and the association between the GRS and the maximum IOP, mean VCDR, and phenotype (HTG or NTG) of POAG was evaluated. As the GRS increased, the maximum IOP (P = 0.012) and VCDR (P = 0.010) significantly increased. The GRS (9.1±1.9) in patients with HTG was significantly higher (P = 0.011) than that (8.7±1.8) in control subjects. The patients with GRS≥12 as a cut-off value had a 2.54 times higher (P = 0.0085) risk on HTG (maximum IOP≥22mmHg) compared with all patients. The IOP-related GRS approach substantiated that the IOP and VCDR were increased by the additive effects of IOP-related genetic variants in POAG. The high IOP-related GRS in patients with HTG but not NTG shows that there are differences in the genetic background between HTG and NTG and supports the notion that the phenotype (HTG or NTG) in patients with POAG depends on the additive effects of IOP-related genetic variants. The above-mentioned cut-off value of IOP-related GRS may be clinically useful for predicting the risk of IOP elevation.</p></div

Whole Exome Analysis Identifies Frequent <i>CNGA1</i> Mutations in Japanese Population with Autosomal Recessive Retinitis Pigmentosa

<div><p>Objective</p><p>The purpose of this study was to investigate frequent disease-causing gene mutations in autosomal recessive retinitis pigmentosa (arRP) in the Japanese population.</p><p>Methods</p><p>In total, 99 Japanese patients with non-syndromic and unrelated arRP or sporadic RP (spRP) were recruited in this study and ophthalmic examinations were conducted for the diagnosis of RP. Among these patients, whole exome sequencing analysis of 30 RP patients and direct sequencing screening of all <i>CNGA1</i> exons of the other 69 RP patients were performed.</p><p>Results</p><p>Whole exome sequencing of 30 arRP/spRP patients identified disease-causing gene mutations of <i>CNGA1</i> (four patients), <i>EYS</i> (three patients) and <i>SAG</i> (one patient) in eight patients and potential disease-causing gene variants of <i>USH2A</i> (two patients), <i>EYS</i> (one patient), <i>TULP1</i> (one patient) and <i>C2orf71</i> (one patient) in five patients. Screening of an additional 69 arRP/spRP patients for the <i>CNGA1</i> gene mutation revealed one patient with a homozygous mutation.</p><p>Conclusions</p><p>This is the first identification of <i>CNGA1</i> mutations in arRP Japanese patients. The frequency of <i>CNGA1</i> gene mutation was 5.1% (5/99 patients). <i>CNGA1</i> mutations are one of the most frequent arRP-causing mutations in Japanese patients.</p></div

Result of multiple linear regression analysis using the maximum IOP as a dependent variable.

<p>Result of multiple linear regression analysis using the maximum IOP as a dependent variable.</p

Sequence data of all six identified <i>CNGA1</i> mutations in this study.

<p>A-1 to F-1 show the normal sequence data for the <i>CNGA1</i> gene. A-2 to F-2 show the sequence data for heterozygous <i>CNGA1</i> mutations (c.191delG, c.265delC, c.G860A, c.G1271A, c.1429delG and c.G2042C, respectively). A-3 and B-3 show the sequence data for homozygous <i>CNGA1</i> mutations (c.191delG and c.265delC).</p

Association between the phenotype (HTG or NTG) of primary open-angle glaucoma and the additive effects of multi-locus IOP-related genetic variants.

<p>The IOP-related genetic risk score calculated as the total number of risk alleles of the 9 IOP-related genetic variants in patients with HTG was significantly higher (P = 0.040, analysis of variance followed by Bonferroni post hoc test) than that in the control subjects. IOP: intraocular pressure, HTG: high tension glaucoma, NTG: normal tension glaucoma.</p

Pedigrees identified with arRP-causing mutations or potential arRP-causing variants.

<p>The solid squares (male) and circles (female) represent affected patients. The proband of each family is indicated by a black arrow. Unaffected family members are represented by white icons. The slash symbol indicates deceased individuals. The doubled line indicates consanguineous marriage. The generation number is shown on the left.</p

Association between the IOP-related GRS and the relative ratio of HTG patients to control subjects.

<p>When the ratio (255 HTG patients/246 control subjects) of all HTG patients (maximum IOP≥22mmHg) to all control subjects (maximum IOP≤21mmHg) was set as 1, the ratio (29 HTG patients/11 control subjects) of HTG to control in patients with the IOP-related GRS calculated as the total number of risk alleles of the 9 IOP-related genetic variants ≥12 was 2.54, which was significantly larger (Chi-square test) than that in all patients. IOP: intraocular pressure, GRS: genetic risk score, HTG: high tension glaucoma.</p

Result of multiple linear regression analysis using the VCDR as a dependent variable.

<p>Result of multiple linear regression analysis using the VCDR as a dependent variable.</p

Result of a multiple linear regression analysis using the maximum IOP as a dependent variable.

<p>Result of a multiple linear regression analysis using the maximum IOP as a dependent variable.</p