A Genome-Wide Association Study for Host Resistance to Ostreid Herpesvirus in Pacific Oysters (Crassostrea gigas)

Ostreid herpesvirus (OsHV) can cause mass mortality events in Pacific oyster aquaculture. While various factors impact on the severity of outbreaks, it is clear that genetic resistance of the host is an important determinant of mortality levels. This raises the possibility of selective breeding strategies to improve the genetic resistance of farmed oyster stocks, thereby contributing to disease control. Traditional selective breeding can be augmented by use of genetic markers, either via marker-assisted or genomic selection. The aim of the current study was to investigate the genetic architecture of resistance to OsHV in Pacific oyster, to identify genomic regions containing putative resistance genes, and to inform the use of genomics to enhance efforts to breed for resistance. To achieve this, a population of approximate to 1,000 juvenile oysters were experimentally challenged with a virulent form of OsHV, with samples taken from mortalities and survivors for genotyping and qPCR measurement of viral load. The samples were genotyped using a recently-developed SNP array, and the genotype data were used to reconstruct the pedigree. Using these pedigree and genotype data, the first high density linkage map was constructed for Pacific oyster, containing 20,353 SNPs mapped to the ten pairs of chromosomes. Genetic parameters for resistance to OsHV were estimated, indicating a significant but low heritability for the binary trait of survival and also for viral load measures (h2 0.12 - 0.25). A genome-wide association study highlighted a region of linkage group 6 containing a significant QTL affecting host resistance. These results are an important step toward identification of genes underlying resistance to OsHV in oyster, and a step toward applying genomic data to enhance selective breeding for disease resistance in oyster aquaculture.Peer reviewe

Detection of Quantitative Trait Loci (QTL) Related to Grilsing and Late Sexual Maturation in Atlantic Salmon (Salmo salar)

In Atlantic salmon aquaculture, early sexual maturation represents a major problem for producers. This is especially true for grilse, which mature after one sea winter before reaching a desirable harvest weight, rather than after two sea winters. Salmon maturing as grilse have a much lower market value than later maturing individuals. For this reason, most companies desire fish that grow fast and mature late. Marker-assisted selection has the potential to improve the efficiency of selection against early maturation and for late sexual maturation; however, studies identifying age of sexual maturation-related genetic markers are lacking for Atlantic salmon. Therefore, we used a 6.5K single-nucleotide polymorphism (SNP) array to genotype five families from the Mainstream Canada broodstock program and search for SNPs associated with early (grilsing) or late sexual maturation. There were 529 SNP loci that were variable across all five families, and this was the set that was used for quantitative trait loci (QTL) analysis. GridQTL identified two chromosomes, Ssa10 and Ssa21, containing QTL related to grilsing. In contrast, only one QTL, on Ssa18, was found linked to late maturation in Atlantic salmon. Our previous work on these five families did not identify genome-wide significant growth-related QTL on Ssa10, Ssa21, or Ssa18. Therefore, taken together, these results suggest that both grilsing and late sexual maturation are controlled independently of one another and also from growth-related traits. The identification of genomic regions associated with grilsing or late sexual maturation provide an opportunity to incorporate this information into selective breeding programs that will enhance Atlantic salmon farming

Detailed insights into pan-European population structure and inbreeding in wild and hatchery Pacific oysters (Crassostrea gigas) revealed by genome-wide SNP data.

Cultivated bivalves are important not only because of their economic value, but also due to their impacts on natural ecosystems. The Pacific oyster (Crassostrea gigas) is the world's most heavily cultivated shellfish species and has been introduced to all continents except Antarctica for aquaculture. We therefore used a medium-density single nucleotide polymorphism (SNP) array to investigate the genetic structure of this species in Europe, where it was introduced during the 1960s and has since become a prolific invader of coastal ecosystems across the continent. We analyzed 21,499 polymorphic SNPs in 232 individuals from 23 localities spanning a latitudinal cline from Portugal to Norway and including the source populations of Japan and Canada. We confirmed the results of previous studies by finding clear support for a southern and a northern group, with the former being indistinguishable from the source populations indicating the absence of a pronounced founder effect. We furthermore conducted a large-scale comparison of oysters sampled from the wild and from hatcheries to reveal substantial genetic differences including significantly higher levels of inbreeding in some but not all of the sampled hatchery cohorts. These findings were confirmed by a smaller but representative SNP dataset generated using restriction site-associated DNA sequencing. We therefore conclude that genomic approaches can generate increasingly detailed insights into the genetics of wild and hatchery produced Pacific oysters

Spanish medical students’ attitudes and views towards Mental Health and Psychiatry: a multicentric cross-sectional study.

Objective The aim of this study is to investigate the attitudes towards mental illness and psychiatry among fifth year Spanish medical students. Methods The study included 171 students from three medical schools located in different areas of Spain: Cádiz; UCA (n= 113), Madrid; San Pablo-CEU (n=22), and Barcelona; UAB (n=36). They responded, prior to their undergraduate medical course in psychiatry, to the AMI questionnaire to measure the attitudes towards mental illness and to Balon’s adapted questionnaire to investigate their view towards psychiatry. Results The students (93.4 %) had a positive attitude towards mental illness (AMI). Attitudes towards psychiatry were fairly positive with a few negative views, specifically regarding the role of psychiatrists (items 11 and 13) and the prestige of the specialty (item 16). There were some statistically significant differences between the three medical schools in the perception of psychiatry as a medical discipline. A better attitude towards mental illness was associated with a better view of the overall merits of psychiatry. Conclusions Findings suggest that Spanish medical students do not have a negative attitude towards mental illness and they have a good perception of psychiatry, although there are still some misconceptions about this specialty. These student’s attitudes could favor an appropriate management of patients suffering from mental illness

Fanconi-BRCA pathway mutations in childhood T-cell acute lymphoblastic leukemia

BRCA2 (also known as FANCD1) is a core component of the Fanconi pathway and suppresses transformation of immature T-cells in mice. However, the contribution of Fanconi-BRCA pathway deficiency to human T-cell acute lymphoblastic leukemia (T-ALL) remains undefined. We identified point mutations in 9 (23%) of 40 human T-ALL cases analyzed, with variant allele fractions consistent with heterozygous mutations early in tumor evolution. Two of these mutations were present in remission bone marrow specimens, suggesting germline alterations. BRCA2 was the most commonly mutated gene. The identified Fanconi-BRCA mutations encode hypomorphic or null alleles, as evidenced by their inability to fully rescue Fanconi-deficient cells from chromosome breakage, cytotoxicity and/or G2/M arrest upon treatment with DNA cross-linking agents. Disabling the tumor suppressor activity of the Fanconi-BRCA pathway is generally thought to require biallelic gene mutations. However, all mutations identified were monoallelic, and most cases appeared to retain expression of the wild-type allele. Using isogenic T-ALL cells, we found that BRCA2 haploinsufficiency induces selective hypersensitivity to ATR inhibition, in vitro and in vivo. These findings implicate Fanconi-BRCA pathway haploinsufficiency in the molecular pathogenesis of T-ALL, and provide a therapeutic rationale for inhibition of ATR or other druggable effectors of homologous recombination

T-Lymphoblastic Lymphoma Cells Express High Levels of BCL2, S1P1, and ICAM1, Leading to a Blockade of Tumor Cell Intravasation

The molecular events underlying the progression of T-lymphoblastic lymphoma (T-LBL) to acute T-lymphoblastic leukemia (T-ALL) remain elusive. In our zebrafish model, concomitant overexpression of bcl-2 with Myc accelerated T-LBL onset while inhibiting progression to T-ALL. The T-LBL cells failed to invade the vasculature and showed evidence of increased homotypic cell-cell adhesion and autophagy. Further analysis using clinical biopsy specimens revealed autophagy and increased levels of BCL2, S1P1, and ICAM1 in human T-LBL compared with T-ALL. Inhibition of S1P1 signaling in T-LBL cells led to decreased homotypic adhesion in vitro and increased tumor cell intravasation in vivo. Thus, blockade of intravasation and hematologic dissemination in T-LBL is due to elevated S1P1 signaling, increased expression of ICAM1, and augmented homotypic cell-cell adhesion.Stem Cell and Regenerative Biolog

Development of genomic markers associated to growth-related traits and sex determination in lumpfish (Cyclopterus lumpus)

Cleaner fish species have gained great importance in the control of sea lice, among them, lumpfish (Cyclopterus lumpus) has become one of the most popular. Lumpfish life cycle has been closed, and hatchery reproduction is now possible, however, current production is reliant on wild caught broodstock to meet the increasing demand. Selective breeding practices are called to play an important role in the successful breeding of most aquaculture species, including lumpfish. In this study, we analysed a lumpfish population for the identification of genomic markers linked to production traits. Sequencing of RAD libraries allowed us to identify, 7193 informative markers within the sampled individuals. Genome wide association analysis for sex, weight, condition factor and standard length was performed. One single major QTL region was identified for sex, while nine QTL regions were detected for weight, and three QTL regions for standard length. A total of 177 SNP markers of interest (from QTL regions) and 399 high Fst SNP markers were combined in a low-density panel, useful to obtain relevant genetic information from lumpfish populations. Moreover, a robust combined subset of 29 SNP markers (10 associated to sex, 14 to weight and 18 to standard length) provided over 90% accuracy in predicting the animal's phenotype by machine learning. Overall, our findings provide significant insights into the genetic control of important traits in lumpfish and deliver important genomic resources that will facilitate the establishment of selective breeding programmes in lumpfish