scholarly journals Pathway-level analysis of genome-wide circadian dynamics in diverse tissues in rat and mouse

Author(s):  
Alison Acevedo ◽  
Panteleimon D. Mavroudis ◽  
Debra DuBois ◽  
Richard R. Almon ◽  
William J. Jusko ◽  
...  
2019 ◽  
Author(s):  
Brenda F. Owens ◽  
Deepu Mathew ◽  
Christine H. Diepenbrock ◽  
Tyler Tiede ◽  
Di Wu ◽  
...  

ABSTRACTRapid development and adoption of biofortified, provitamin A-dense orange maize (Zea mays L.) varieties could be facilitated by a greater understanding of the natural variation underlying kernel color, including as relates to carotenoid biosynthesis and retention in maize grain. Greater abundance of carotenoids in maize kernels is generally accompanied by deeper orange color, useful for distinguishing provitamin A-dense varieties to consumers. While kernel color can be scored and selected with high-throughput, low-cost phenotypic methods within breeding selection programs, it remains to be well established as to what would be the logical genetic loci to target for selection for kernel color. We conducted a genome-wide association study of maize kernel color, as determined by colorimetry, in 1,651 yellow and orange inbreds from the Ames maize inbred panel. Associations were found with y1, encoding the first committed step in carotenoid biosynthesis, and with dxs2, which encodes the enzyme responsible for the first committed step in the biosynthesis of the isoprenoid precursors of carotenoids. These genes logically could contribute to overall carotenoid abundance and thus kernel color. The lcyE and zep1 genes, which can affect carotenoid composition, were also found to be associated with colorimeter values. A pathway-level analysis, focused on genes with a priori evidence of involvement in carotenoid biosynthesis and retention, revealed associations for dxs3 and dmes1, involved in isoprenoid biosynthesis; ps1 and vp5, within the core carotenoid pathway; and vp14, involved in cleavage of carotenoids. Collectively, these identified genes appear relevant to the accumulation of kernel color.


2013 ◽  
Vol 3 (8) ◽  
pp. 1287-1299 ◽  
Author(s):  
Alexander E. Lipka ◽  
Michael A. Gore ◽  
Maria Magallanes-Lundback ◽  
Alex Mesberg ◽  
Haining Lin ◽  
...  

2019 ◽  
pp. g3.400040.2019 ◽  
Author(s):  
Brenda F. Owens ◽  
Deepu Mathew ◽  
Christine H. Diepenbrock ◽  
Tyler Tiede ◽  
Di Wu ◽  
...  

2013 ◽  
Vol 3 (1) ◽  
pp. 119-129 ◽  
Author(s):  
Charles R Farber

Abstract Genome-wide association studies (GWAS) have emerged as the method of choice for identifying common variants affecting complex disease. In a GWAS, particular attention is placed, for obvious reasons, on single-nucleotide polymorphisms (SNPs) that exceed stringent genome-wide significance thresholds. However, it is expected that many SNPs with only nominal evidence of association (e.g., P < 0.05) truly influence disease. Efforts to extract additional biological information from entire GWAS datasets have primarily focused on pathway-enrichment analyses. However, these methods suffer from a number of limitations and typically fail to lead to testable hypotheses. To evaluate alternative approaches, we performed a systems-level analysis of GWAS data using weighted gene coexpression network analysis. A weighted gene coexpression network was generated for 1918 genes harboring SNPs that displayed nominal evidence of association (P ≤ 0.05) from a GWAS of bone mineral density (BMD) using microarray data on circulating monocytes isolated from individuals with extremely low or high BMD. Thirteen distinct gene modules were identified, each comprising coexpressed and highly interconnected GWAS genes. Through the characterization of module content and topology, we illustrate how network analysis can be used to discover disease-associated subnetworks and characterize novel interactions for genes with a known role in the regulation of BMD. In addition, we provide evidence that network metrics can be used as a prioritizing tool when selecting genes and SNPs for replication studies. Our results highlight the advantages of using systems-level strategies to add value to and inform GWAS.


2018 ◽  
Vol 61 (1) ◽  
pp. 8.25.1-8.25.24 ◽  
Author(s):  
Tin Nguyen ◽  
Cristina Mitrea ◽  
Sorin Draghici
Keyword(s):  

2007 ◽  
Vol 17 (10) ◽  
pp. 1537-1545 ◽  
Author(s):  
S. Draghici ◽  
P. Khatri ◽  
A. L. Tarca ◽  
K. Amin ◽  
A. Done ◽  
...  

2017 ◽  
Author(s):  
Chiara Fabbri ◽  
Katherine E. Tansey ◽  
Roy H. Perlis ◽  
Joanna Hauser ◽  
Neven Henigsberg ◽  
...  

AbstractGenome-wide association studies have generally failed to identify polymorphisms associated with antidepressant response. Possible reasons include limited coverage of genetic variants that this study tried to address by exome genotyping and dense imputation.A meta-analysis of Genome-Based Therapeutic Drugs for Depression (GENDEP) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies was performed at SNP, gene and pathway level. Coverage of genetic variants was increased compared to previous studies by adding exome genotypes to previously available genome-wide data and using the Haplotype Reference Consortium panel for imputation. Standard quality control was applied. Phenotypes were symptom improvement and remission after 12 weeks of antidepressant treatment. NEWMEDS consortium samples and Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) served for replication.7,062,950 SNPs were analysed in GENDEP (n=738) and STAR*D (n=1409). rs116692768 (p=1.80e-08, ITGA9 (integrin alpha 9)) and rs76191705 (p=2.59e-08, NRXN3 (neurexin 3)) were significantly associated with symptom improvement during citalopram/escitalopram treatment. At gene level, no consistent effect was found. At pathway level, the Gene Ontology terms GO:0005694 (chromosome) and GO:0044427 (chromosomal part) were associated with improvement (corrected p=0.007 and 0.045, respectively). The association between rs116692768 and symptom improvement was replicated in PGRN-AMPS (p=0.047), while rs76191705 was not. The two SNPs did not replicate in NEWMEDS.ITGA9 codes for a membrane receptor for neurotrophins and NRXN3 is a transmembrane neuronal adhesion receptor involved in synaptic differentiation. Despite their meaningful biological rationale for being involved in antidepressant effect, no convincing replication was achieved. Further studies may help in clarifying their role.


2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Aarti Gautam ◽  
Seid Muhie ◽  
Nabarun Chakraborty ◽  
Allison Hoke ◽  
Rasha Hammamieh ◽  
...  

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