DNA double-strand breaks relieve USF-mediated repression of Dβ2 germline transcription in developing thymocytes.

Activation of germline promoters is central to V(D)J recombinational accessibility, driving chromatin remodeling, nucleosome repositioning, and transcriptional read-through of associated DNA. We have previously shown that of the two TCRβ locus (Tcrb) D segments, Dβ1 is flanked by an upstream promoter that directs its transcription and recombinational accessibility. In contrast, transcription within the DJβ2 segment cluster is initially restricted to the J segments and only redirected upstream of Dβ2 after D-to-J joining.

The relationship between glaucoma medication adherence, eye drop technique, and visual field defect severity.

Objective: The purpose of the study was to examine (1) how patient adherence and eye drop technique were associated with visual field defect severity and (2) how general glaucoma adherence self-efficacy and eye drop technique self-efficacy were related to visual field defect severity.

Design: Cross-sectional study conducted at a single private practice site.

Participants: Patients using eye drops for their glaucoma.

Validation of a short version of the glaucoma medication self-efficacy questionnaire.

Aims: The aims of this study were: (1) to examine whether the original glaucoma medication adherence and eye drop technique self-efficacy scales could be shortened for easier use in practice settings; and (2) to validate these scales against objective medication adherence measures.

Methods: Prospective study conducted at a single private practice site. We measured subjects' adherence to glaucoma medications through Medication Event Monitoring System (MEMS) devices and assessed eye drop instillation technique by video-recording.

Common polygenic variation contributes to risk of schizophrenia and bipolar disorder.

Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits, with heritability estimated at up to 80%. We performed a genome-wide association study of 3,322 European individuals with schizophrenia and 3,587 controls. Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia.

An objective evaluation of eyedrop instillation in patients with glaucoma.

Objectives: To evaluate the performance of patients with ocular hypertension and glaucoma who are experienced in the instillation of topical ocular hypotensive medications.

Methods: We conducted a prospective, open-label study at a single private practice site. We enrolled 139 patients with a diagnosis of glaucoma or ocular hypertension who used 1 or more topical ocular hypotensive medications for at least 6 months and who instilled their own medications.

Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene.

Autism is a genetically complex neurodevelopmental syndrome in which language deficits are a core feature. We describe results from two complimentary approaches used to identify risk variants on chromosome 7 that likely contribute to the etiology of autism. A two-stage association study tested 2758 SNPs across a 10 Mb 7q35 language-related autism QTL in AGRE (Autism Genetic Resource Exchange) trios and found significant association with Contactin Associated Protein-Like 2 (CNTNAP2), a strong a priori candidate.

High density SNP association study of a major autism linkage region on chromosome 17.

A region on chromosome 17 has recently been highlighted as linked to autism (MIM[209850]) in multiple studies and evidence has accumulated suggesting that male-only families (those families that have produced only affected males) provide the major contribution to linkage at this locus. In an attempt to comprehensively test for association of common variants to autism within the region on chromosome 17 defined in Stone et al. (Stone, J.

Replication of autism linkage: fine-mapping peak at 17q21.

Autism is a heritable but genetically complex disorder characterized by deficits in language and in reciprocal social interactions, combined with repetitive and stereotypic behaviors. As with many genetically complex disorders, numerous genome scans reveal inconsistent results. A genome scan of 345 families from the Autism Genetic Resource Exchange (AGRE) (AGRE_1), gave the strongest evidence of linkage at 17q11-17q21 in families with no affected females.

Evidence for sex-specific risk alleles in autism spectrum disorder.

We investigated the genetic aspects of the large sex bias in the prevalence of autism spectrum disorder by monitoring changes in linkage when the family set for an affected sibling pair genome scan is subdivided on the basis of the sex of affected children. This produces a significant excess in the total number of linkage peaks (P=1.3 x 10(-8)) and identifies a major male-specific linkage peak at chromosome 17q11 (P<.

Genetic linkage of attention-deficit/hyperactivity disorder on chromosome 16p13, in a region implicated in autism.

Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed behavioral disorder in childhood and likely represents an extreme of normal behavior. ADHD significantly impacts learning in school-age children and leads to impaired functioning throughout the life span. There is strong evidence for a genetic etiology of the disorder, although putative alleles, principally in dopamine-related pathways suggested by candidate-gene studies, have very small effect sizes.