Multi-trait genomic selection for weevil resistance, growth, and wood quality in Norway spruce.

Plantation-grown trees have to cope with an increasing pressure of pest and disease in the context of climate change, and breeding approaches using genomics may offer efficient and flexible tools to face this pressure. In the present study, we targeted genetic improvement of resistance of an introduced conifer species in Canada, Norway spruce (Picea abies (L.) Karst.), to the native white pine weevil (Pissodes strobi Peck). We developed single- and multi-trait genomic selection (GS) models and selection indices considering the relationships between weevil resistance, intrinsic wood quality, and growth traits. Weevil resistance, acoustic velocity as a proxy for mechanical wood stiffness, and average wood density showed moderate-to-high heritability and low genotype-by-environment interactions. Weevil resistance was genetically positively correlated with tree height, height-to-diameter at breast height (DBH) ratio, and acoustic velocity. The accuracy of the different GS models tested (GBLUP, threshold GBLUP, Bayesian ridge regression, BayesCπ) was high and did not differ among each other. Multi-trait models performed similarly as single-trait models when all trees were phenotyped. However, when weevil attack data were not available for all trees, weevil resistance was more accurately predicted by integrating genetically correlated growth traits into multi-trait GS models. A GS index that corresponded to the breeders' priorities achieved near maximum gains for weevil resistance, acoustic velocity, and height growth, but a small decrease for DBH. The results of this study indicate that it is possible to breed for high-quality, weevil-resistant Norway spruce reforestation stock with high accuracy achieved from single-trait or multi-trait GS.

A catalog of annotated high-confidence SNPs from exome capture and sequencing reveals highly polymorphic genes in Norway spruce (Picea abies).

BACKGROUND: Norway spruce [Picea abies (L.) Karst.] is ecologically and economically one of the most important conifer worldwide. Our main goal was to develop a large catalog of annotated high confidence gene SNPs that should sustain the development of genomic tools for the conservation of natural and domesticated genetic diversity resources, and hasten tree breeding efforts in this species. RESULTS: Targeted sequencing was achieved by capturing P. abies exome with probes previously designed from the sequenced transcriptome of white spruce (Picea glauca (Moench) Voss). Capture efficiency was high (74.5%) given a high level of exome conservation between the two species. Using stringent criteria, we delimited a set of 61,771 high-confidence SNPs across 13,543 genes. To validate SNPs, a high-throughput genotyping array was developed for a subset of 5571 predicted SNPs representing as many different gene loci, and was used to genotype over 1000 trees. The estimated true positive rate of the resource was 84.2%, which was comparable with the genotyping success rate obtained for P. abies control SNPs recycled from previous genotyping efforts. We also analyzed SNP abundance across various gene functional categories. Several GO terms and gene families involved in stress response were found over-represented in highly polymorphic genes. CONCLUSION: The annotated high-confidence SNP catalog developed herein represents a valuable genomic resource, being representative of over 13 K genes distributed across the P. abies genome. This resource should serve a variety of population genomics and breeding applications in Norway spruce.

Expression of the growth hormone/insulin-like growth factor axis during Balb/c thymus ontogeny and effects of growth hormone upon ex vivo T cell differentiation.

AIMS: We address the question of the expression and the role of the growth hormone/insulin-like growth factor (GH/IGF) axis in the thymus. METHODS: Using RT-qPCR, the expression profile of various components of the somatotrope GH/IGF axis was measured in different thymic cell types and during thymus embryogenesis in Balb/c mice. The effect of GH on T cell differentiation was explored via thymic organotypic culture. RESULTS: Transcription of Gh, Igf1, Igf2 and their related receptors predominantly occurred in thymic epithelial cells (TEC), while a low level of Gh and Igf1r transcription was also evidenced in thymic T cells (thymocytes). Gh, Ghr, Ins2, Igf1, Igf2, and Igfr1 displayed distinct expression profiles depending on the developmental stage. The protein concentrations of IGF-1 and IGF-2 were in accordance with the profile of their gene expression. In fetal thymus organ cultures (FTOC) derived from Balb/c mice, treatment with exogenous GH resulted in a significant increase of double negative CD4-CD8- T cells and CD4+ T cells, together with a decrease in double positive CD4+CD8+ T cells. These changes were inhibited by concomitant treatment with GH and the GH receptor (GHR) antagonist pegvisomant. However, GH treatment also induced a significant decrease in FTOC Gh, Ghr and Igf1 expression. CONCLUSION: These data show that the thymotropic properties of the somatotrope GH/IGF-1 axis involve an interaction between exogenous GH and GHR expressed by TEC. Since thymic IGF-1 is not increased by GH treatment, the effects of GH upon T cell differentiation could implicate a different local growth factor or cytokine.

The role of the thymus in the integrated evolution of the recombinase-dependent adaptive immune response and the neuroendocrine system.

Before being able to react against infectious non-self-antigens, the immune system has to be educated in recognition and tolerance of neuroendocrine self-proteins. This sophisticated educational process takes place only in the thymus. The development of an autoimmune response directed to neuroendocrine glands has been shown to result from a thymus dysfunction in programming immunological self-tolerance to neuroendocrine-related antigens. This thymus dysfunction leads to a breakdown of immune homeostasis with an enrichment of 'forbidden' self-reactive T cells and a deficiency in self-antigen-specific natural regulatory T cells in the peripheral T lymphocyte repertoire. A large number of neuroendocrine self-antigens are expressed by the thymic epithelium, under the control of the autoimmune regulator (AIRE) gene/protein in the medulla. Based on the close homology and cross-tolerance between thymic type 1 diabetes-related self-antigens and peripheral antigens targeted in ß-cells by autoimmunity, a novel type of vaccination is currently developed for the prevention and cure of type 1 diabetes. If this approach were found to be effective in reprogramming immunological tolerance that is absent or broken in this disease, it could pave the way for the design of negative/tolerogenic self-vaccines against other endocrine and organ-specific autoimmune disorders.

Thymic self-antigens for the design of a negative/tolerogenic self-vaccination against type 1 diabetes.

Before being able to react against infectious nonself-antigens, the immune system has to be educated in the recognition and tolerance of neuroendocrine proteins and this critical process takes place only in the thymus. The development of the autoimmune diabetogenic response results from a thymus dysfunction in programing central self-tolerance to pancreatic insulin-secreting islet beta cells, leading to the breakdown of immune homeostasis with an enrichment of islet beta-cell reactive effector T cells and a deficiency of beta-cell specific natural regulatory T cells (nTregs) in the peripheral T-lymphocyte repertoire. Insulin-like growth factor 2 (IGF-2) is the dominant member of the insulin family expressed during fetal life by the thymic epithelium under the control of the autoimmune regulator (AIRE) gene/protein. The very low degree of insulin gene transcription in normal murine and human thymus explains why the insulin protein is poorly tolerogenic as demonstrated in many studies, including the failure of all clinical trials that have attempted immune tolerance to islet beta cells via various methods of insulin administration. On the basis of the close homology and crosstolerance between insulin, the primary T1D autoantigen, and IGF-2, the dominant self-antigen of the insulin family, a novel type of vaccination, so-called 'negative/tolerogenic self-vaccination', is currently being developed for the prevention and cure of T1D. If this approach were found to be effective for reprograming immunological tolerance in T1D, it could pave the way for the design of other self-vaccines against autoimmune endocrine diseases, as well as other organ-specific autoimmune diseases.