Transferability of cupped oyster EST (Expressed Sequence Tag)-derived SNP (Single Nucleotide Polymorphism) markers to related crassostrea and ostrea species

Single nucleotide polymorphisms (SNPs) are widely acknowledged as the marker of choice for many genetic and genomic applications because they show co-dominant inheritance, are highly abundant across genomes and are suitable for high-throughput genotyping. Here we evaluated the applicability of SNP markers developed from Crassostrea gigas and C. virginica expressed sequence tags (ESTs) in closely related Crassostrea and Ostrea species. A total of 213 putative interspecific level SNPs were identified from re-sequencing data in six amplicons, yielding on average of one interspecific level SNP per seven bp. High polymorphism levels were observed and the high success rate of transferability show that genic EST-derived SNP markers provide an efficient method for rapid marker development and SNP discovery in closely related oyster species. The six EST-SNP markers identified here will provide useful molecular tools for addressing questions in molecular ecology and evolution studies including for stock analysis (pedigree monitoring) in related oyster taxa.

Optimizing de novo transcriptome assembly and extending genomic resources for striped catfish (Pangasianodon hypophthalmus)

Striped catfish (Pangasianodon hypophthalmus) is a commercially important freshwater fish used in inland aquaculture in the Mekong Delta, Vietnam. The culture industry is facing a significant challenge however from saltwater intrusion into many low topographical coastal provinces across the Mekong Delta as a result of predicted climate change impacts. Developing genomic resources for this species can facilitate the production of improved culture lines that can withstand raised salinity conditions, and so we have applied high-throughput Ion Torrent sequencing of transcriptome libraries from six target osmoregulatory organs from striped catfish as a genomic resource for use in future selection strategies. We obtained 12,177,770 reads after trimming and processing with an average length of 97 bp. De novo assemblies were generated using CLC Genomic Workbench, Trinity and Velvet/Oases with the best overall contig performance resulting from the CLC assembly. De novo assembly using CLC yielded 66,451 contigs with an average length of 478 bp and N50 length of 506 bp. A total of 37,969 contigs (57%) possessed significant similarity with proteins in the non-redundant database. Comparative analyses revealed that a significant number of contigs matched sequences reported in other teleost fishes, ranging in similarity from 45.2% with Atlantic cod to 52% with zebrafish. In addition, 28,879 simple sequence repeats (SSRs) and 55,721 single nucleotide polymorphisms (SNPs) were detected in the striped catfish transcriptome. The sequence collection generated in the current study represents the most comprehensive genomic resource for P. hypophthalmus available to date. Our results illustrate the utility of next-generation sequencing as an efficient tool for constructing a large genomic database for marker development in non-model species.

Conserved gene structure and function of interleukin-10 in teleost fish

Interleukin-10 (IL-10) is an important immunoregulatory cytokine produced by various types of cells. Researchers describe here the isolation and characterization of olive flounder IL-10 (ofIL-10) cDNA and genomic organization. The ofIL-10 gene encodes a 187 amino acid protein and is composed of a five exon/four intron structure, similar to other known IL-10 genes. The ofIL-10 promoter sequence analysis shows a high level of homology in putative binding sites for transcription factors which are sufficient for transcriptional regulation ofIL-10. Important structural residues are maintained in the ofIL-10 protein including the four cysteines responsible for the two intra-chain disulfide bridges reported for human IL-10 and two extra cysteine residues that exist only in fish species. The phylogenetic analysis clustered ofIL-10 with other fish IL-10s and apart from mammalian IL-10 molecules. Quantitative real-time Polymerase Chain Reaction (PCR) analysis demonstrated ubiquitous ofIL-10 gene expression in the 13 tissues examined. Additionally, the induction of ofIL-10 gene expression was observed in the kidney tissue from olive flounder infected with bacteria (Edawardsiella tarda) or virus (Viral Hemorrhagic Septicemia Virus; VHSV). These data indicate that IL-10 is an important immune regulator that is conserved strictly genomic organization and function during the evolution of vertebrate immunity.

Australian patients using a cardiac-diabetes web-based intervention program: Contributions to person-centered clinical practice

Rationale, aims and objectives: Patients with both cardiac disease and diabetes have poorer health outcomes than patients with only one chronic condition. While evidence indicates that internet based interventions may improve health outcomes for patients with a chronic disease, there is no literature on internet programs specific to cardiac patients with comorbid diabetes. Therefore this study aimed to develop a specific web-based program, then to explore patients’ perspectives on the usefulness of a new program. Methods: The interpretive approach using semi-structured interviews on a purposive sample of eligible patients with type 2 diabetes and a cardiac condition in a metropolitan hospital in Brisbane, Australia. Thematic analysis was undertaken to describe the perceived usefulness of a newly developed Heart2heart webpage. Results: Themes identified included confidence in hospital health professionals and reliance on doctors to manage conditions. Patients found the webpage useful for managing their conditions at home. Conclusions: The new Heart2heart webpage provided a positive and useful resource. Further research on to determine the potential influence of this resource on patients’ self-management behaviours is paramount. Implications for practice include using multimedia strategies for providing information to patients’ comorbidities of cardiac disease and type 2 diabetes, and further development on enhancement of such strategies

Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus

Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey-Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey-Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han-Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p<5×10-8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p=4.6×10-8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98-1.14; p=0.17), displaying high degree of heterogeneity (I2=57%; Qhet p=0.0006). Under Han-Eskin alternative random effects model the summary effect was significant (p=0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures.

Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10−8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10−4, Bonferroni corrected), of which six reached P < 5 × 10−8, including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: Quantifying the epidemiological transition

Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5–89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.

Signifying Angels : Analyses and Interpretations of Rautavaara s Instrumental Compositions

The subject of doctoral thesis is the analysis and interpretation of instrumental pieces composed by Einojuhani Rautavaara (b. 1928) that have been given angelic titles: Archangel Michael Fighting the Antichrist from the suite Icons (1955)/Before the Icons (2006), Angels and Visitations (1978), the Double Bass Concerto Angel of Dusk (1980), Playgrounds for Angels (1981)and the Seventh Symphony Angel of Light (1994). The aim of the work is to find those musical elements common to these pieces that distinguish them from Rautavaara s other works and to determine if they could be thought of as a series. I prove that behind the common elements and titles stands the same extramusical idea the figure of an angel that the composer has described in his commentaries. The thesis is divided into three parts. Since all of the compositions possess titles that refer to the spiritual symbol of an angel, the first part offers a theoretical background to demonstrate the significant role played by angels in various religions and beliefs, and the means by which music has attempted to represent this symbol throughout history. This background traces also Rautavaara s aesthetic attitude as a spiritual composer whose output can be studied with reference to his extramusical interests including literature, psychology, painting, philosophy and myths. The second part focuses on the analysis of the instrumental compositions with angelic titles, without giving consideration to their commentaries and titles. The analyses concentrate in particular on those musical features that distinguish these pieces from Rautavaara s other compositions. In the third part these musical features are interpreted as symbols of the angel through comparison with vocal and instrumental pieces which contain references to the character of an angel, structures of mythical narration, special musical expressions, use of instruments and aspects of brightness. Finally I explore the composer s interpretative codes, drawing on Rilke s cycle of poems Ten Duino Elegies and Jung s theory of archetypes, and analyze the instrumental pieces with angelic titles in the light of the theory of musical ekphrasis.

Nykytaiteen alkukuvat : Postjungilainen estetiikka nykykuvataiteen tulkintavälineenä

Tutkimus tarkastelee analyyttisen psykologian isän C. G. Jungin teorian sekä jungilaisten ja postjungilaisten teorioiden soveltuvuutta nykykuvataiteen tarkasteluun. Tutkimus esittelee jungilaista estetiikkaa kattavasti suomeksi ja soveltaa sitä postjungilaisesti nykykuvataiteen tulkintaan. Kumpaakaan ei ole aiemmin tehty estetiikan alalla Suomessa. Tutkimusaineistona on käytetty painettujen lähteiden lisäksi esimerkiksi haastatteluita ja aiheeseen liittyviä seminaareja. Jung ei itse muodostanut yhtenäistä taiteen tulkintateoriaa. Sekä psykologian että taidefilosofian puolella on viitattu yleisellä tasolla joihinkin jungilaisiin tulkintamahdollisuuksiin, mutta jungilaista estetiikkaa ei ole kehitetty kuvataiteen tulkintaan eikä varsinkaan nykykuvataiteen tulkintaan soveltuvaksi välineeksi. Kirjallisuuden tutkimuksen puolella jungilaisen näkökulman soveltaminen tulkintaan on yleisempää, myös Suomessa. Suomessa Jung-tutkimus on kuitenkin vähäistä ja pintapuolista sekä yleisesti ottaen että erityisesti työn aiheen kannalta. Työn alussa esitellään tutkimuksellinen ja teoreettinen kansainvälinen ja kansallinen viitekehys. Tämän jälkeen esitellään tutkimuksen kannalta tärkeät jungilaiset käsitteet, kuten arkkityyppi, kollektiivinen tiedostamaton ja symboli. Aiheelle keskeistä jungilaista symboli-käsitettä tarkastellaan laajasti ja pohditaan tämän sijoittumista taiteen tutkimuksen kentällä suhteessa esimerkiksi muihin estetiikan symbolikäsityksiin. Tutkielmassa yhdistellään jungilaisten ja postjungilaisten ajattelijoiden teorioita ja tutkimusmetodeja ja sovelletaan tästä ajattelumatriisista johdettua postjungilaista taiteen tulkintavälinettä kulttuurisidonnaisen nykykuvataiteen tulkintaan. Tässä tutkimuksessa postjungilaista estetiikkaa sovelletaan taiteen tulkintaan innovatiivisesti ja tieteellisesti tukeutumatta vain mielleyhtymiin. Työssä kehitellään erityisesti myös terapiassa käytettyä jungilaista amplifikaatio-menetelmää nykykuvataiteen tulkintavälineeksi, minkä jälkeen amplifikaatio-menetelmän sovelluksella tulkitaan Maaria Wirkkalan Vakain aikein (2006) -installaatioteosta. Työssä keskitytään yhteisölliseen ja kollektiiviseen näkökulmaan teostulkinnassa. Taiteesta voidaan tätä kautta löytää jotain ajatonta ja yhteistä. Postjungilaisen nykytaiteen tulkinnan avulla voi tunnistaa ja nostaa näitä asioita keskusteluun. Amplifikaatiota ei ole aiemmin sovellettu samalla tavalla. Lopuksi käsitellään tämän postjungilaisen taideteostulkinnan tuloksia ja jäsennetään niitä suhteessa teoreettisen viitekehyksen käsitteisiin sekä tarkastellaan jatkotutkimusmahdollisuuksia. Tutkimus osoittaa, että esitelty postjungilainen tarkastelu sopii nykykuvataiteen tulkintavälineeksi erityisesti kun halutaan järjestelmällisesti etsiä ja tarkastella nykykuvataideteosten yliyksilöllisiä viittausmahdollisuuksia. Avainsanat: Estetiikka, taidefilosofia, taide, tulkinta, Jung, jungilaisuus, postjungilaisuus, nykytaide, nykykuvataide, kuvataide, tiedostamaton, kollektiivinen, kollektiivinen tiedostamaton, arkkityypit, symbolit, amplifikaatio

"Olen enemmän alkanut pohtimaan ja sanomaan ääneen mitä ajattelen" : ammatillinen kehittyminen ja yhteisöllinen palaute päiväkodin työtiimeissä

I have more often thought over what I am thinking and also I have often told it to others - professional development and collegial feedback on kindergarten teams. The need for professional feedback surfaces year after year in enquiries made among staff members in the field of early childhood education. Because the pressure to be effective adds to the workload of the heads of kindergartens, there are few opportunities to give staff concrete feedback on a daily basis. Because peers are able to observe each other close at hand, their reciprocal feedback can compensate for that of the kindergarten head. In this study the practical training process of collegial feedback is studied and also the opportunities for feedback as a means of supporting professional development in the context of kindergarten. The development project involving the entire kindergarten community (N=21) was implemented in 2003-2004 through three developing cycles. The Johar´s Window , produced by Luft and Jung with the Model of Situational Leadership by Hersey and Blanchard, acted as a theoretical frame of reference. It has been used in this study both for its qualitative and its quantitative methods. The data were carried out through questions, interviews, diaries, written descriptions and monthly evaluations. The qualitative and quantitative methods were also used in analysing the data. The results showed that during the training process, the staff as a giver of feedback moved from the professional basic level to the professional maturity level. Their awareness of both their own and their peers´ know-how expanded from the initial state to the final state. It became evident that team size is the essential key element in the practise of giving feedback to team members. The team atmosphere and the commitment of the team members are in significant factors in the training of giving and receiving feedback. As a result of analyses, delivering feedback was grouped into three categories: developmental feedback, descriptive feedback and either supportive or destructive feedback. Receiving feedback was likewise groupped into three categories: aspiring to develop, unaccommodating and accepting. The ability to control feelings improved along with the skills of giving feedback; it was possible to analyse development through the professional development model represented in the theory of the study. The results showed that professional know-how of other kinds also developed during the process. Giving feedback among fellow workers enables team members to receive feedback everyday. Training to give feedback means examining a field of professional know-how and also formulating shared rules. The results of this study give support to previous studies that have emphasised practical training in natural circumstances. Keywords: feedback, professional development, learning at work

A mega-analysis of genome-wide association studies for major depressive disorder

Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18 759 independent and unrelated subjects of recent European ancestry (9240 MDD cases and 9519 controls). In the MDD replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases and 50 695 controls). We also conducted a cross-disorder meta-analysis using 819 autosomal SNPs with P<0.0001 for either MDD or the Psychiatric GWAS Consortium bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP cases/7775 controls). No SNPs achieved genome-wide significance in the MDD discovery phase, the MDD replication phase or in pre-planned secondary analyses (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal onset MDD or typical-like MDD from a latent class analyses of the MDD criteria). In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5 x 10(-8)), and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083-53 822 102, minimum P=5.9 x 10(-9) at rs2535629). Although this is the largest genome-wide analysis of MDD yet conducted, its high prevalence means that the sample is still underpowered to detect genetic effects typical for complex traits. Therefore, we were unable to identify robust and replicable findings. We discuss what this means for genetic research for MDD. The 3p21.1 MDD-BIP finding should be interpreted with caution as the most significant SNP did not replicate in MDD samples, and genotyping in independent samples will be needed to resolve its status.

Painting of Felix Mendelssohn-Bartholdy by Eduard Magnus Portraits Men

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Development of type I genetic markers from expressed sequence tags in highly polymorphic species

Expressed sequence tag (EST) databases provide a primary source of nuclear DNA sequences for genetic marker development in non-model organisms. To date, the process has been relatively inefficient for several reasons: - 1) priming site polymorphism in the template leads to inferior or erratic amplification; - 2) introns in the target amplicon are too large and/or numerous to allow effective amplification under standard screening conditions, and; - 3) at least occasionally, a PCR primer straddles an exon–intron junction and is unable to bind to genomic DNA template. The first is only a minor issue for species or strains with low heterozygosity but becomes a significant problem for species with high genomic variation, such as marine organisms with extremely large effective population sizes. Problems arising from unanticipated introns are unavoidable but are most pronounced in intron-rich species, such as vertebrates and lophotrochozoans. We present an approach to marker development in the Pacific oyster Crassostrea gigas, a highly polymorphic and intron-rich species, which minimizes these problems, and should be applicable to other non-model species for which EST databases are available. Placement of PCR primers in the 3′ end of coding sequence and 3′ UTR improved PCR success rate from 51% to 97%. Almost all (37 of 39) markers developed for the Pacific oyster were polymorphic in a small test panel of wild and domesticated oysters.

The extremophile Nicotiana benthamiana has traded viral defence for early vigour

A single lineage of Nicotiana benthamiana is widely used as a model plant1 and has been instrumental in making revolutionary discoveries about RNA interference (RNAi), viral defence and vaccine production. It is peerless in its susceptibility to viruses and its amenability in transiently expressing transgenes2,3. These unparalleled characteristics have been associated both positively and negatively with a disruptive insertion in the RNA-dependent RNA polymerase 1 gene, Rdr14–6. For a plant so routinely used in research, the origin, diversity and evolution of the species, and the basis of its unusual abilities, have been relatively unexplored. Here, by comparison with wild accessions from across the spectrum of the species’ natural distribution, we show that the laboratory strain of N. benthamiana is an extremophile originating from a population that has retained a mutation in Rdr1 for ∼0.8 Myr and thereby traded its defence capacity for early vigour and survival in the extreme habitat of central Australia. Reconstituting Rdr1 activity in this isolate provided protection. Silencing the functional allele in a wild strain rendered it hypersusceptible and was associated with a doubling of seed size and enhanced early growth rate. These findings open the way to a deeper understanding of the delicate balance between protection and vigour.