Genetic associations of LYN with systemic lupus erythematosus.

We targeted LYN, a src-tyosine kinase involved in B-cell activation, in case-control association studies using populations of European-American, African-American and Korean subjects. Our combined European-derived population, consisting of 2463 independent cases and 3131 unrelated controls, shows significant association with rs6983130 in a female-only analysis with 2254 cases and 2228 controls (P=1.1 x 10(-4), odds ratio (OR)=0.81 (95% confidence interval: 0.73-0.90)). This single nucleotide polymorphism (SNP) is located in the 5' untranslated region within the first intron near the transcription initiation site of LYN. In addition, SNPs upstream of the first exon also show weak and sporadic association in subsets of the total European-American population. Multivariate logistic regression analysis implicates rs6983130 as a protective factor for systemic lupus erythematosus (SLE) susceptibility when anti-dsDNA, anti-chromatin, anti-52 kDa Ro or anti-Sm autoantibody status were used as covariates. Subset analysis of the European-American female cases by American College of Rheumatology classification criteria shows a reduction in the risk of hematological disorder with rs6983130 compared with cases without hematological disorders (P=1.5 x 10(-3), OR=0.75 (95% CI: 0.62-0.89)). None of the 90 SNPs tested show significant association with SLE in the African American or Korean populations. These results support an association of LYN with European-derived individuals with SLE, especially within autoantibody or clinical subsets.

Accumulation of stress and inducer-dependent plant-cell-wall-degrading enzymes during asexual development in Aspergillus nidulans.

Determination and interpretation of fungal gene expression profiles based on digital reconstruction of expressed sequenced tags (ESTs) are reported. A total of 51,524 DNA sequence files processed with PipeOnline resulted in 9775 single and 5660 contig unique ESTs, 31.2% of a typical fungal transcriptome. Half of the unique ESTs shared homology with genes in public databases, 35.8% of which are functionally defined and 64.2% are unclear or unknown. In Aspergillus nidulans 86% of transcripts associate with intermediate metabolism functions, mainly related to carbohydrate, amino acid, protein, and peptide biosynthesis. During asexual development, A. nidulans unexpectedly accumulates stress response and inducer-dependent transcripts in the absence of an inducer. Stress response genes in A. nidulans ESTs total 1039 transcripts, contrasting with 117 in Neurospora crassa, a 14.3-fold difference. A total of 5.6% of A. nidulans ESTs implicate inducer-dependent cell wall degradation or amino acid acquisition, 3.5-fold higher than in N. crassa. Accumulation of stress response and inducer-dependent transcripts suggests general derepression of cis-regulation during terminal asexual development.