Cucumber is an economically important crop as well as a model system for sex determination studies and plant vascular biology. Here we report the draft genome sequence of Cucumis sativus var. sativus L., assembled using a novel combination of traditional Sanger and next-generation Illumina GA sequencing technologies to obtain 72.2-fold genome coverage. The absence of recent whole-genome duplication, along with the presence of few tandem duplications, explains the small number of genes in the cucumber. Our study establishes that five of the cucumber's seven chromosomes arose from fusions of ten ancestral chromosomes after divergence from Cucumis melo. The sequenced cucumber genome affords insight into traits such as its sex expression, disease resistance, biosynthesis of cucurbitacin and 'fresh green' odor. We also identify 686 gene clusters related to phloem function. The cucumber genome provides a valuable resource for developing elite cultivars and for studying the evolution and function of the plant vascular system.

No abstract

Age-related macular degeneration (AMD) is a major cause of blindness, but presents differently in Europeans and Asians. Here, we perform a genome-wide and exome-wide association study on 2,119 patients with exudative AMD and 5,691 controls, with independent replication in 4,226 patients and 10,289 controls, all of East Asian descent, as part of The Genetics of AMD in Asians (GAMA) Consortium. We find a strong association between CETP Asp442Gly (rs2303790), an East Asian-specific mutation, and increased risk of AMD (odds ratio (OR)=1.70, P=5.60 × 10−22). The AMD risk allele (442Gly), known to protect from coronary heart disease, increases HDL cholesterol levels by 0.17 mmol l−1 (P=5.82 × 10−21) in East Asians (n=7,102). We also identify three novel AMD loci: C6orf223 Ala231Ala (OR=0.78, P=6.19 × 10−18), SLC44A4 Asp47Val (OR=1.27, P=1.08 × 10−11) and FGD6 Gln257Arg (OR=0.87, P=2.85 × 10−8). Our findings suggest that some of the genetic loci conferring AMD susceptibility in East Asians are shared with Europeans, yet AMD in East Asians may also have a distinct genetic signature.

Exfoliation syndrome (XFS) is the commonest known risk factor for secondary glaucoma and a significant cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A have been previously associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results between populations, and to identify new variants associated with XFS. We identified a rare, protective allele at LOXL1 (p.407Phe, OR = 25, P =2.9 × 10−14) through deep resequencing of XFS cases and controls from 9 countries. This variant results in increased cellular adhesion strength compared to the wild-type (p.407Tyr) allele. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10−8). Index variants at the new loci map to chromosomes 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS, and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.

Exfoliation syndrome (XFS) is the commonest recognizable cause of open angle glaucoma world-wide. To better understand the etiology of XFS, we conducted a genome-wide association study (GWAS) on 1,484 patients and 1,188 controls from Japan, and followed up the most significant findings on a further 6,901 patients and 20,727 controls from 17 countries across 6 continents. We discovered a significant association between a new locus (CACNA1A rs4926244) and increased susceptibility to XFS (Odds ratio [OR] = 1.16, P = 3.36 × 10−11). Although overwhelming association at the LOXL1 locus was confirmed, the key SNP marker (LOXL1 rs4886776) demonstrated allelic reversal depending on ethnic grouping (In Japanese: ORA-allele= 9.87, P = 2.13 × 10−217; In non-Japanese: ORA-allele= 0.49, P = 2.35 × 10−31). Our findings represent the first genetic locus outside of LOXL1 which surpasses genome-wide significance for XFS, and provides insight into the biology and pathogenesis of the disease.

Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10−33), we observed one SNP showing significant association to POAG (CDC7–TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10−8). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.

No abstract

Acta Ophthalmol. 2011: 89: e72–e74 Abstract. Purpose:  Retinoblastoma is the most frequent primary intraocular tumour and is rapidly gaining importance in Asia. As the survival is markedly dependent on early diagnosis and as information on that is not available from East Asia, we assessed the time interval between symptoms detection and therapy of children treated in the Beijing TongRen Eye Hospital. Methods:  The retrospective study consisted of all patients who were treated in the study period from January 1987 to November 2006 in the Beijing TongRen Hospital and for whom the data on delay in diagnosis, age, clinical appearance and histological tumour features were available. Results:  The inclusion criteria were met by 572 patients (326 boys) with a mean age of 2.6 ± 1.8. Mean interval between first detection of symptoms and clinical diagnosis and therapy was 4.1 ± 5.9 months (range: 3–36 months). A diagnostic delay of 2 months or >6 months was found for 337 (59%) children and 98 (17%) children, respectively. Diagnostic delay was significantly (p < 0.001) the longest in the 2‐ to 4‐year‐old group (5.5 ± 7.4 months). It decreased from the study period 1987–1991 to the period 2002–2006 (p < 0.001). It was significantly associated with the clinical appearance (p = 0.001) and histological finding (p = 0.008). Conclusions:  Delay in the diagnosis of retinoblastoma depended on the age of the children, study period, and clinical and histological stage. Because the prognosis is markedly influenced by tumour stage, further improvements in the alertness of parents, family doctors and paediatricians and in the medical infrastructure in China may be addressed.