Orthogonal patterning of multiple biomolecules using an organic fluorinated resist and imprint lithography

The ability to spatially deposit multiple biomolecules onto a single surface with high-resolution while retaining biomolecule stability and integrity is critical to the development of micro- and nanoscale biodevices. While conventional lithographic patterning methods are attractive for this application, they typically require the use of UV exposure and/or harsh solvents and imaging materials, which may be damaging to fragile biomolecules. Here, we report the development of a new patterning process based on a fluorinated patterning material that is soluble in hydrofluoroether solvents, which we show to be benign to biomolecules, including proteins and DNA. We demonstrate the implementation of these materials into an orthogonal processing system for patterning multibiomolecule arrays by imprint lithography at room temperature. We further showcase this method's capacity for fabricating patterns of receptor-specific ligands for fundamental cell studies. © 2013 American Chemical Society

Genome-Wide Association Study Identification of Novel Loci Associated with Airway Responsiveness in Chronic Obstructive Pulmonary Disease

Pathogenesis and treatment of chronic pulmonary disease

Genome-Wide Association Study Identification of Novel Loci Associated with Airway Responsiveness in Chronic Obstructive Pulmonary Disease

Increased airway responsiveness is linked to lung function decline and mortality in subjects with chronic obstructive pulmonary disease (COPD); however, the genetic contribution to airway responsiveness remains largely unknown. A genome-wide association study (GWAS) was performed using the Illumina (San Diego, CA) Human660W-Quad BeadChip on European Americans with COPD from the Lung Health Study. Linear regression models with correlated meta-analyses, including data from baseline (n = 2,814) and Year 5 (n = 2,657), were used to test for common genetic variants associated with airway responsiveness. Genotypic imputation was performed using reference 1000 Genomes Project data. Expression quantitative trait loci (eQTL) analyses in lung tissues were assessed for the top 10 markers identified, and immunohistochemistry assays assessed protein staining for SGCD and MYH15. Four genes were identified within the top 10 associations with airway responsiveness. Markers on chromosome 9p21.2 flanked by LINGO2 met a predetermined threshold of genome-wide significance (P <9.57x10(-8)). Markers on chromosomes 3q13.1 (flanked by MYH15), 5q33 (SGCD), and 6q21 (PDSS2) yielded suggestive evidence of association (9.57x10(-8) <

African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans

Background: Asthma is the most common chronic disease in children, occurring at higher frequencies and with more severe disease in children with African ancestry. Methods: We tested for association with haplotypes at the most replicated and significant childhood-onset asthma locus at 17q12-q21 and asthma in European American and African American children. Following this, we used whole-genome sequencing data from 1060 African American and 100 European American individuals to identify novel variants on a high-risk African American–specific haplotype. We characterized these variants in silico using gene expression and ATAC-seq data from airway epithelial cells, functional annotations from ENCODE, and promoter capture (pc)Hi-C maps in airway epithelial cells. Candidate causal variants were then assessed for correlation with asthma-associated phenotypes in African American children and adults. Results: Our studies revealed nine novel African-specific common variants, enriched on a high-risk asthma haplotype, which regulated the expression of GSDMA in airway epithelial cells and were associated with features of severe asthma. Using ENCODE annotations, ATAC-seq, and pcHi-C, we narrowed the associations to two candidate causal variants that are associated with features of T2 low severe asthma. Conclusions: Previously unknown genetic variation at the 17q12-21 childhood-onset asthma locus contributes to asthma severity in individuals with African ancestries. We suggest that many other population-specific variants that have not been discovered in GWAS contribute to the genetic risk for asthma and other common diseases. © 2022, The Author(s).Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

A multi-ethnic genome-wide association study of 21000 cases and 95000 controls identifies 11 novel genetic variants associated with atopic dermatitis.

Background: Atopic dermatitis (AD) is a highly heritable common chronic inflammatory skin disease. Twenty-one genetic risk loci have been previously identified. The largest genome-wide association study (GWAS) to date included around 5000 cases and 20 000 controls (of only European origin) and identified 3 risk loci, putting AD some way behind many other complex common diseases that have been studied in much larger numbers and for which many more risk loci have been identified. Method: We conducted the world’s largest GWAS of AD. Our discovery cohort consisted of 21 409 cases and 95 445 controls from 26 studies and used data imputed to the 1000 genomes reference panel (\u3e 15 million variants). In addition to carrying out a fixed effects genome-wide meta-analysis of European individuals, we also included Japanese, Latino and African-American individuals in a multi-ethnic meta-analysis (using MANTRA software). Replication was sought in 30 582 cases and 226 518 controls from 17 studies. Results: The discovery phase identified 27 loci associated with AD (11 novel). A gene-set enrichment analysis (using MAGENTA) identified 38 significantly enriched gene-sets (FDR \u3c 0.05) out of a total of \u3e 10 000 tested, and 9 additional SNPs (with P \u3c 10-5) were taken forward to replication. Eleven of the 20 novel SNPs replicated and reached genome-wide significance. One particularly interesting association involved a series of SNPs near CD207, a gene selectively expressed in Langerhans cells (dendritic cells of the epidermis), putatively involved in antigen uptake and processing. These SNPs also showed strong association with CD207 expression in skin tissue in the MuTHER study (P = 2x10-10). Thus, our results suggest a possible role for genetic factors influencing epithelial dendritic cell function in the aetiology of AD. In addition to the novel loci we also identified four secondary signals at known loci. Furthermore our results show a substantial genetic overlap with other immune-mediated diseases, particularly inflammatory bowel disease (IBD). Thirty-nine of 163 SNPs robustly associated with IBD in a recent GWAS were at least nominally associated (P \u3c 0.05) with AD in our analysis (34 with the same direction of effect). Conclusion: Our results bring the total number of AD risk loci discovered to 31. All new loci include candidate genes with roles in regulating environmental sensing and adaptive immune responses, underscoring the important contribution of immune components to AD pathogenesis