Gene expression in blood is associated with risperidone response in children with autism spectrum disorders.

Children with autism spectrum disorders (ASDs) often have severe behavioral problems. Not all children with these problems respond to atypical antipsychotic medications; therefore, we investigated whether peripheral blood gene expression before treatment with risperidone, an atypical antipsychotic, was associated with improvements in severe behavioral disturbances 8 weeks following risperidone treatment in 42 ASD subjects (age 112.7±51.2 months). Exon expression levels in blood before risperidone treatment were compared with pre-post risperidone change in Aberrant Behavior Checklist-Irritability (ABC-I) scores. Expression of exons within five genes was correlated with change in ABC-I scores across all risperidone-treated subjects: GBP6, RABL5, RNF213, NFKBID and RNF40 (α<0.001). RNF40 is located at 16p11.2, a region implicated in autism and schizophrenia. Thus, these genes expressed before treatment were associated with subsequent clinical response. Future studies will be needed to confirm these results and determine whether this expression profile is associated with risperidone response in other disorders, or alternative antipsychotic response within ASD.

Transient ischemic attacks characterized by RNA profiles in blood.

OBJECTIVE: Transient ischemic attacks (TIA) are common. Though systemic inflammation and thrombosis are associated with TIA, further study may provide insight into TIA pathophysiology and possibly lead to the development of treatments specifically targeted to TIA. We sought to determine whether gene expression profiles in blood could better characterize the proinflammatory and procoagulant states in TIA patients. METHODS: RNA expression in blood of TIA patients (n = 26) was compared to vascular risk factor control subjects without symptomatic cardiovascular disease (n = 26) using Affymetrix U133 Plus 2.0 microarrays. Differentially expressed genes in TIA were identified by analysis of covariance and evaluated with cross-validation and functional analyses. RESULTS: Patients with TIA had different patterns of gene expression compared to controls. There were 480 probe sets, corresponding to 449 genes, differentially expressed between TIA and controls (false discovery rate correction for multiple comparisons, p ≤ 0.05, absolute fold change ≥1.2). These genes were associated with systemic inflammation, platelet activation, and prothrombin activation. Hierarchical cluster analysis of the identified genes suggested the presence of 2 patterns of RNA expression in patients with TIA. Prediction analysis identified a set of 34 genes that discriminated TIA from controls with 100% sensitivity and 100% specificity. CONCLUSION: Patients with recent TIA have differences of gene expression in blood compared to controls. The 2 gene expression profiles associated with TIA suggests heterogeneous responses between subjects with TIA that may provide insight into cause, risk of stroke, and other TIA pathophysiology.

Construction and evaluation of cDNA libraries for large-scale expressed sequence tag sequencing in wheat (Triticum aestivum L.).

A total of 37 original cDNA libraries and 9 derivative libraries enriched for rare sequences were produced from Chinese Spring wheat (Triticum aestivum L.), five other hexaploid wheat genotypes (Cheyenne, Brevor, TAM W101, BH1146, Butte 86), tetraploid durum wheat (T. turgidum L.), diploid wheat (T. monococcum L.), and two other diploid members of the grass tribe Triticeae (Aegilops speltoides Tausch and Secale cereale L.). The emphasis in the choice of plant materials for library construction was reproductive development subjected to environmental factors that ultimately affect grain quality and yield, but roots and other tissues were also included. Partial cDNA expressed sequence tags (ESTs) were examined by various measures to assess the quality of these libraries. All ESTs were processed to remove cloning system sequences and contaminants and then assembled using CAP3. Following these processing steps, this assembly yielded 101,107 sequences derived from 89,043 clones, which defined 16,740 contigs and 33,213 singletons, a total of 49,953 "unigenes." Analysis of the distribution of these unigenes among the libraries led to the conclusion that the enrichment methods were effective in reducing the most abundant unigenes and to the observation that the most diverse libraries were from tissues exposed to environmental stresses including heat, drought, salinity, or low temperature.

Frequencies of Ty1- copia and Ty3- gypsy retroelements within the Triticeae EST databases.

The frequency of Ty1- copia-type and Ty3- gypsy-type retrotransposons in the International Triticeae EST Consortium (ITEC) database (61,942 sequences: 82% wheat, 10% barley, 8% rye) and the DuPont EST database (86,628 wheat sequences) was estimated using BLASTN searches. These ESTs were obtained from 94 cDNA libraries from different tissues (leaves, roots, spikes, flowers and seeds) and different growing conditions, excluding subtracted and normalized cDNA libraries. Triticeae EST databases were screened using four different Ty1- -copia-type, 12 reverse transcriptase sequences, and three Ty3- gypsy-type Triticeae retrotransposon sequences. Using a selection threshold of BLASTN scores higher than 100 or E values smaller than e(-20), 0.145% of the ESTs were found to be significantly similar to at least one of the retrotransposons used in the search (0.064% Ty1- copia, 0.081% Ty3- gypsy). This percentage increased to 0.176% when the BLASTN threshold was changed to E