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Distribution of COL8A2 and COL8A1 gene variants in Caucasian primary open angle glaucoma patients with thin central corneal thickness
Purpose: One approach to identify genes that contribute to common complex ocular disorders such as primary open angle glaucoma (POAG) is to study the genetic determinates of endophenotypes that are defined by underlying pre-disposing heritable quantitative traits such as central corneal thickness (CCT). Collagen VIII is a major component of Descemetâs membrane and studies in mice have indicated that targeted inactivation of the genes encoding the collagen type 8 alpha1 (Col8a1) and collagen type 8 alpha2 (Col8a2) subunits (COL8A1 and COL8A2) results in thinning of the corneal stroma and of Descemetâs membrane. The purpose of this study is to evaluate COL8A1 and COL8A2 as candidate genes for thin CCT in human POAG patients. Methods: 100 Caucasian POAG patients were enrolled in this study. The entire COL8A1 and COL8A2 coding sequence was determined in 8 patients with CCT586 ”m (one standard deviation above the mean). Selected COL8A2 exons containing variants of interest were sequenced in the full POAG cohort. Association and quantitative trait analyses were performed. Results: Three patients with CCT less than 513 ”m and advanced POAG were found to have missense changes in COL8A2; two patients had a previously identified mutation, R155Q and one had a novel change, P678L (p=0.0035, Fisherâs exact test). Missense changes were not found in any of the patients with CCT>513 ”m and missense changes in the COL8A1 gene were not found in any patient. One common COL8A2 SNP, rs274754 was also statistically associated with CCT (p=0.018). Conclusions: In this study we have identified COL8A2 missense changes in a group of Caucasian patients with very thin CCT and advanced POAG. These results suggest that DNA sequence variants in the COL8A2 gene may be associated with thin corneas in some glaucoma patients. Further study of COL8A2 variants in other patient populations, especially those with thinner CCT such as African-Americans would provide further support for a role of COL8A2 in corneal thickness and in glaucoma
Pathway Analysis Integrating Genome-Wide and Functional Data Identifies PLCG2 as a Candidate Gene for Age-Related Macular Degeneration
PURPOSE. Age-related macular degeneration (AMD) is the worldwide leading cause of blindness
among the elderly. Although genome-wide association studies (GWAS) have identified AMD
risk variants, their roles in disease etiology are not well-characterized, and they only explain a
portion of AMD heritability.
METHODS. We performed pathway analyses using summary statistics from the International
AMD Genomics Consortiumâs 2016 GWAS and multiple pathway databases to identify
biological pathways wherein genetic association signals for AMD may be aggregating. We
determined which genes contributed most to significant pathway signals across the databases.
We characterized these genes by constructing protein-protein interaction networks and
performing motif analysis.
RESULTS. We determined that eight genes (C2, C3, LIPC, MICA, NOTCH4, PLCG2, PPARA, and
RAD51B) ââdriveââ the statistical signals observed across pathways curated in the Kyoto
Encyclopedia of Genes and Genomes (KEGG), Reactome, and Gene Ontology (GO) databases.
We further refined our definition of statistical driver gene to identify PLCG2 as a candidate
gene for AMD due to its significant gene-level signals (P < 0.0001) across KEGG, Reactome,
GO, and NetPath pathways.
CONCLUSIONS. We performed pathway analyses on the largest available collection of advanced
AMD cases and controls in the world. Eight genes strongly contributed to significant pathways
from the three larger databases, and one gene (PLCG2) was central to significant pathways from
all four databases. This is, to our knowledge, the first study to identify PLCG2 as a candidate
gene for AMD based solely on genetic burden. Our findings reinforce the utility of integrating in
silico genetic and biological pathway data to investigate the genetic architecture of AMD
Search for Neutral Q-balls in Super-Kamiokande II
A search for Q-balls induced groups of successive contained events has been
carried out in Super-Kamiokande II with 541.7 days of live time.
Neutral Q-balls would emit pions when colliding with nuclei, generating a
signal of successive contained pion events along a track. No candidate for
successive contained event groups has been found in Super-Kamiokande II, so
upper limits on the possible flux of such Q-balls have been obtained.Comment: 5 pages, 5 figures, Submitted to Phys. Lett.
Calibration of Super-Kamiokande Using an Electron Linac
In order to calibrate the Super-Kamiokande experiment for solar neutrino
measurements, a linear accelerator (LINAC) for electrons was installed at the
detector. LINAC data were taken at various positions in the detector volume,
tracking the detector response in the variables relevant to solar neutrino
analysis. In particular, the absolute energy scale is now known with less than
1 percent uncertainty.Comment: 24 pages, 16 figures, Submitted to NIM
Measurement of a small atmospheric ratio
From an exposure of 25.5~kiloton-years of the Super-Kamiokande detector, 900
muon-like and 983 electron-like single-ring atmospheric neutrino interactions
were detected with momentum MeV/, MeV/, and
with visible energy less than 1.33 GeV. Using a detailed Monte Carlo
simulation, the ratio was measured to be , consistent with previous results from the
Kamiokande, IMB and Soudan-2 experiments, and smaller than expected from
theoretical models of atmospheric neutrino production.Comment: 14 pages with 5 figure
Measurement of radon concentrations at Super-Kamiokande
Radioactivity from radon is a major background for observing solar neutrinos
at Super-Kamiokande. In this paper, we describe the measurement of radon
concentrations at Super-Kamiokande, the method of radon reduction, and the
radon monitoring system. The measurement shows that the current low-energy
event rate between 5.0 MeV and 6.5 MeV implies a radon concentration in the
Super-Kamiokande water of less than 1.4 mBq/m.Comment: 11 pages, 4 figure
Lichenometric dating (lichenometry) and the biology of the lichen genus rhizocarpon:challenges and future directions
Lichenometric dating (lichenometry) involves the use of lichen measurements to estimate the age of exposure of various substrata. Because of low radial growth rates and considerable longevity, species of the crustose lichen genus Rhizocarpon have been the most useful in lichenometry. The primary assumption of lichenometry is that colonization, growth and mortality of Rhizocarpon are similar on surfaces of known and unknown age so that the largest thalli present on the respective faces are of comparable age. This review describes the current state of knowledge regarding the biology of Rhizocarpon and considers two main questions: (1) to what extent does existing knowledge support this assumption; and (2) what further biological observations would be useful both to test its validity and to improve the accuracy of lichenometric dates? A review of the Rhizocarpon literature identified gaps in knowledge regarding early development, the growth rate/size curve, mortality, regeneration, competitive effects, colonization, and succession on rock surfaces. The data suggest that these processes may not be comparable on different rock surfaces, especially in regions where growth rates and thallus turnover are high. In addition, several variables could differ between rock surfaces and influence maximum thallus size, including rate and timing of colonization, radial growth rates, environmental differences, thallus fusion, allelopathy, thallus mortality, colonization and competition. Comparative measurements of these variables on surfaces of known and unknown age may help to determine whether the basic assumptions of lichenometry are valid. Ultimately, it may be possible to take these differences into account when interpreting estimated dates
Follow-up of loci from the International Genomics of Alzheimer's Disease Project identifies TRIP4 as a novel susceptibility gene
To follow-up loci discovered by the International Genomics of Alzheimer's Disease Project, we attempted independent replication of 19 single nucleotide polymorphisms (SNPs) in a large Spanish sample (FundaciĂł ACE data set; 1808 patients and 2564 controls). Our results corroborate association with four SNPs located in the genes INPP5D, MEF2C, ZCWPW1 and FERMT2, respectively. Of these, ZCWPW1 was the only SNP to withstand correction for multiple testing (P=0.000655). Furthermore, we identify TRIP4 (rs74615166) as a novel genome-wide significant locus for Alzheimer's disease risk (odds ratio=1.31; confidence interval 95% (1.19-1.44); P=9.74 Ă 10 - 9)
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