Rare variants in optic disc area gene CARD10 enriched in primary open-angle glaucoma

Background: Genome-wide association studies (GWAS) have identified association of common alleles with primary open-angle glaucoma (POAG) and its quantitative endophenotypes near numerous genes. This study aims to determine whether rare pathogenic variants in these disease-associated genes contribute to POAG. Methods: Participants fulfilled strict inclusion criteria of advanced POAG at a young age of diagnosis. Myocilin mutation carriers were excluded using direct sequencing. Whole exome sequencing was performed on 187 glaucoma cases and 103 local screened nonglaucoma controls then joint-called with exomes of 993 previously sequenced Australian controls. GWAS-associated genes were assessed for enrichment of rare predicted pathogenic variants in POAG. Significantly enriched genes were compared against Exome Aggregation Consortium (ExAC) public control. Results: Eighty-six GWAS disease or trait-associated glaucoma genes were captured and sequenced. CARD10 showed enrichment after Bonferroni correction for rare variants in glaucoma cases (OR = 13.2, P = 6.94 × 10−5) with mutations identified in 4.28% of our POAG cohort compared to 0.27% in controls. CARD10 was significantly associated with optic disc parameters in previous GWAS. The whole GWAS gene set showed no enrichment in POAG overall (OR = 1.12, P = 0.51). Conclusion: We report here an enrichment of rare predicted pathogenic coding variants within a GWAS-associated locus in POAG (CARD10). These findings indicate that both common and rare pathogenic coding variants in CARD10 may contribute to POAG pathogenesis.Tiger Zhou, Emmanuelle Souzeau, Shiwani Sharma, Owen M. Siggs, Ivan Goldberg, Paul R. Healey, Stuart Graham, Alex W. Hewitt, David A. Mackey, Robert J. Casson, John Landers, Richard Mills, Jonathan Ellis, Paul Leo, Matthew A. Brown, Stuart MacGregor, Kathryn P. Burdon and Jamie E. Crai

Marine diatoms grown in chemostats under silicate or ammonium limitation. III. Cellular chemical composition and morphology of Chaetoceros debilis, Skeletonema costatum , and Thalassiosira gravida

Three marine diatoms, Skeletonema costatum, Chaetoceros debilis , and Thalassiosira gravida were grown under no limitation and ammonium or silicate limitation or starvation. Changes in cell morphology were documented with photomicrographs of ammonium and silicate-limited and non-limited cells, and correlated with observed changes in chemical composition. Cultures grown under silicate starvation or limitation showed an increase in particulate carbon, nitrogen and phosporus and chlorophyll a per unit cell volume compared to non-limited cells; particulate silica per cell volume decreased. Si-starved cells were different from Si-limited cells in that the former contained more particulate carbon and silica per cell volume. The most sensitive indicator of silicate limitation or starvation was the ratio C:Si, being 3 to 5 times higher than the values for non-limited cells. The ratios Si:chlorophyll a and S:P were lower and N:Si was higher than non-limited cells by a factor of 2 to 3. The other ratios, C:N, C:P, C:chlorophyll a , N:chlorophyll a , P:chlorophyll a and N:P were considered not to be sensitive indicators of silicate limitation or starvation. Chlorophyll a , and particulate nitrogen per unit cell volume decreased under ammonium limitation and starvation. NH 4 -starved cells contained more chlorophyll a , carbon, nitrogen, silica, and phosphorus per cell volume than NH 4 -limited cells. N:Si was the most sensitive ratio to ammonium limitation or starvation, being 2 to 3 times lower than non-limited cells. Si:chlorophyll a , P:chlorophyll a and N:P were less sensitive, while the ratios C:N, C:chlorophyll a , N:chlorophyll a , C:Si, C:P and Si:P were the least sensitive. Limited cells had less of the limiting nutrient per unit cell volume than starved cells and more of the non-limiting nutrients (i.e., silica and phosphorus for NH 4 -limited cells). This suggests that nutrient-limited cells rather than nutrient-starved cells should be used along with non-limited cells to measure the full range of potential change in cellular chemical composition for one species under nutrient limitation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46631/1/227_2004_Article_BF00392568.pd

Characteristics and appearance of the normal optic nerve head in 6-year-old children

10.1136/bjo.2010.197426British Journal of Ophthalmology96168-72BJOP

The relationship between retinal arteriolar and venular calibers is genetically mediated, and each is associated with risk of cardiovascular disease

10.1167/iovs.10-5927Investigative Ophthalmology and Visual Science522975-981IOVS

Heidelberg retinal tomography of optic disc and nerve fiber layer in Singapore children: Variations with disc tilt and refractive error

10.1167/iovs.07-0585Investigative Ophthalmology and Visual Science48114939-494

119 loci influencing intraocular pressure provide new insight into primary open angle glaucoma susceptibility and age of onset

Abstract #1177Jamie E. Craig, Alex W. Hewitt, David Mackey, Stuart L Graham, Paul R Healey, Andrew JR White, John Landers, Robert Casson, Emmanuelle Souzeau, Kathryn P Burdon, Puya Gharahkhani, Stuart MacGrego