Additional file 2: of MultiDCoX: Multi-factor analysis of differential co-expression

Functional analysis of joint and individual influence of co-factors on co-expression of genesets. Summary of GO terms and pathways enriched for joint and individual influence of different cofactors on co-expression of genests. Joint influence of co-factors is evident from the number of pathways and GO terms enriched for genesets whose co-expression is affected by more than one co-factor. (DOC 66 kb

Additional file 1: of MultiDCoX: Multi-factor analysis of differential co-expression

Results of Analysis of Breast Cancer Data. Contains all differentially co-expressed genesets with respective differential co-expression model fit (F-test p-value, coefficient value), gene counts, and permutation results over three factors (ER, p53 and Grade) in breast cancer data. Remarks: Grade + indicates higher grade tumor i.e. 2 and 3, while Grade– indicates lower grade tumour i.e. 1. (XLS 804 kb

Analysis of <i>POFUT1</i> Gene Mutation in a Chinese Family with Dowling-Degos Disease

<div><p>Dowling-Degos disease (DDD) is an autosomal dominant genodermatosis characterized by reticular pigmented anomaly mainly affecting flexures. Though <i>KRT5</i> has been identified to be the causal gene of DDD, the heterogeneity of this disease was displayed: for example, <i>POFUT1</i> and <i>POGLUT1</i> were recently identified and confirmed to be additional pathogenic genes of DDD. To identify other DDD causative genes, we performed genome-wide linkage and exome sequencing analyses in a multiplex Chinese DDD family, in which the <i>KRT5</i> mutation was absent. Only a novel 1-bp deletion (c.246+5delG) in <i>POFUT1</i> was found. No other novel mutation or this deletion was detected in <i>POFUT1</i> in a second DDD family and a sporadic DDD case by Sanger Sequencing. The result shows the genetic-heterogeneity and complexity of DDD and will contribute to the further understanding of DDD genotype/phenotype correlations and to the pathogenesis of this disease.</p></div

Family trees of Family I and Family II.

<p>Shown are the pedigree of family I and family II with DDD. The arrow denotes the proband; “Δ” denotes the individuals used in the linkage analysis; “★” denotes the individuals used in exome sequencing analysis, “⧫” denotes the individuals that were Sanger sequenced for <i>POFUT1</i>.</p

Clinical manifestations of DDD.

<p>Reticular hyperpigmentation on the skin of neck and abdomen.</p

The 1-bp deletion in <i>POFUT1</i>.

<p>The Sanger sequencing traces around the position of 1-bp deletion c.246+5delG in one affected and one unaffected individuals of Family I.</p

Additional file 2: Table S2. of Discovery of a novel genetic susceptibility locus on X chromosome for systemic lupus erythematosus

Presenting HaploReg annotation for rs5914778 (Query SNP: rs5914778 and variants with r 2 ≧0.8). (DOC 46 kb

Additional file 3: Table S3. of Discovery of a novel genetic susceptibility locus on X chromosome for systemic lupus erythematosus

Presenting the motifs predicted to be affected by rs5913992 SNP (Regulome DB). (DOC 171 kb

Genome-Wide Linkage, Exome Sequencing and Functional Analyses Identify <i>ABCB6</i> as the Pathogenic Gene of Dyschromatosis Universalis Hereditaria

<div><p>Background</p><p>As a genetic disorder of abnormal pigmentation, the molecular basis of dyschromatosis universalis hereditaria (DUH) had remained unclear until recently when ABCB6 was reported as a causative gene of DUH.</p><p>Methodology</p><p>We performed genome-wide linkage scan using Illumina Human 660W-Quad BeadChip and exome sequencing analyses using Agilent SureSelect Human All Exon Kits in a multiplex Chinese DUH family to identify the pathogenic mutations and verified the candidate mutations using Sanger sequencing. Quantitative RT-PCR and Immunohistochemistry was performed to verify the expression of the pathogenic gene, Zebrafish was also used to confirm the functional role of ABCB6 in melanocytes and pigmentation.</p><p>Results</p><p>Genome-wide linkage (assuming autosomal dominant inheritance mode) and exome sequencing analyses identified <i>ABCB6</i> as the disease candidate gene by discovering a coding mutation (c.1358C>T; p.Ala453Val) that co-segregates with the disease phenotype. Further mutation analysis of <i>ABCB6</i> in four other DUH families and two sporadic cases by Sanger sequencing confirmed the mutation (c.1358C>T; p.Ala453Val) and discovered a second, co-segregating coding mutation (c.964A>C; p.Ser322Lys) in one of the four families. Both mutations were heterozygous in DUH patients and not present in the 1000 Genome Project and dbSNP database as well as 1,516 unrelated Chinese healthy controls. Expression analysis in human skin and mutagenesis interrogation in zebrafish confirmed the functional role of <i>ABCB6</i> in melanocytes and pigmentation. Given the involvement of <i>ABCB6</i> mutations in coloboma, we performed ophthalmological examination of the DUH carriers of <i>ABCB6</i> mutations and found ocular abnormalities in them.</p><p>Conclusion</p><p>Our study has advanced our understanding of DUH pathogenesis and revealed the shared pathological mechanism between pigmentary DUH and ocular coloboma.</p></div

Phenotypes of the microinjected zebrafish.

<p>Morpholinos against exon 6 and exon 8 of <i>zABCB6</i> and wildtype <i>zABCB6</i> mRNA transcript (in case of rescue) were designed and injected into one- to two-cell stage embryos. No obvious phenotypic changes were observed in the morphants (C and D) and rescued (E and F) embryos after 5 days (5pdf) with reference to their uninjected counterparts (A and B).</p