Advanced backcross QTL analysis and comparative mapping with RIL QTL studies and GWAS provide an overview of QTL and marker haplotype diversity for resistance to Aphanomyces root rot in pea (Pisum sativum).

Aphanomyces euteiches is the most damaging soilborne pea pathogen in France. Breeding of pea resistant varieties combining a diversity of quantitative trait loci (QTL) is a promising strategy considering previous research achievements in dissecting polygenic resistance to A. euteiches. The objective of this study was to provide an overview of the diversity of QTL and marker haplotypes for resistance to A. euteiches, by integrating a novel QTL mapping study in advanced backcross (AB) populations with previous QTL analyses and genome-wide association study (GWAS) using common markers. QTL analysis was performed in two AB populations derived from the cross between the susceptible spring pea variety "Eden" and the two new sources of partial resistance "E11" and "LISA". The two AB populations were genotyped using 993 and 478 single nucleotide polymorphism (SNP) markers, respectively, and phenotyped for resistance to A. euteiches in controlled conditions and in infested fields at two locations. GWAS and QTL mapping previously reported in the pea-Aphanomyces collection and from four recombinant inbred line (RIL) populations, respectively, were updated using a total of 1,850 additional markers, including the markers used in the Eden x E11 and Eden x LISA populations analysis. A total of 29 resistance-associated SNPs and 171 resistance QTL were identified by GWAS and RIL or AB QTL analyses, respectively, which highlighted 10 consistent genetic regions confirming the previously reported QTL. No new consistent resistance QTL was detected from both Eden x E11 and Eden x LISA AB populations. However, a high diversity of resistance haplotypes was identified at 11 linkage disequilibrium (LD) blocks underlying consistent genetic regions, especially in 14 new sources of resistance from the pea-Aphanomyces collection. An accumulation of favorable haplotypes at these 11 blocks was confirmed in the most resistant pea lines of the collection. This study provides new SNP markers and rare haplotypes associated with the diversity of Aphanomyces root rot resistance QTL investigated, which will be useful for QTL pyramiding strategies to increase resistance levels in future pea varieties.

An integrative Study Showing the Adaptation to Sub-Optimal Growth Conditions of Natural Populations of Arabidopsis thaliana: A Focus on Cell Wall Changes.

In the global warming context, plant adaptation occurs, but the underlying molecular mechanisms are poorly described. Studying natural variation of the model plant Arabidopsisthaliana adapted to various environments along an altitudinal gradient should contribute to the identification of new traits related to adaptation to contrasted growth conditions. The study was focused on the cell wall (CW) which plays major roles in the response to environmental changes. Rosettes and floral stems of four newly-described populations collected at different altitudinal levels in the Pyrenees Mountains were studied in laboratory conditions at two growth temperatures (22 vs. 15 °C) and compared to the well-described Col ecotype. Multi-omic analyses combining phenomics, metabolomics, CW proteomics, and transcriptomics were carried out to perform an integrative study to understand the mechanisms of plant adaptation to contrasted growth temperature. Different developmental responses of rosettes and floral stems were observed, especially at the CW level. In addition, specific population responses are shown in relation with their environment and their genetics. Candidate genes or proteins playing roles in the CW dynamics were identified and will deserve functional validation. Using a powerful framework of data integration has led to conclusions that could not have been reached using standard statistical approaches.

Diverse types of genomic evidence converge on alcohol use disorder risk genes.

BACKGROUND: Alcohol use disorder (AUD) is one of the most common forms of substance use disorders with a strong contribution of genetic (50%-60%) and environmental factors. Genome-wide association studies (GWAS) have identified a number of AUD-associated variants, including those in alcohol metabolism genes. These genetic variants may modulate gene expression, making individuals more susceptible to AUD. A long-term alcohol consumption can also change the transcriptome patterns of subjects via epigenetic modulations. METHODS: To explore the interactive effect of genetic and epigenetic factors on AUD, we conducted a secondary analysis by integrating GWAS, CNV, brain transcriptome and DNA methylation data to unravel novel AUD-associated genes/variants. We applied the mega-analysis of OR (MegaOR) method to prioritise AUD candidate genes (AUDgenes). RESULTS: We identified a consensus set of 206 AUDgenes based on the multi-omics data. We demonstrated that these AUDgenes tend to interact with each other more frequent than chance expectation. Functional annotation analysis indicated that these AUDgenes were involved in substance dependence, synaptic transmission, glial cell proliferation and enriched in neuronal and liver cells. We obtained a multidimensional evidence that AUD is a polygenic disorder influenced by both genetic and epigenetic factors as well as the interaction of them. CONCLUSION: We characterised multidimensional evidence of genetic, epigenetic and transcriptomic data in AUD. We found that 206 AUD associated genes were highly expressed in liver, brain cerebellum, frontal cortex, hippocampus and pituitary. Our studies provides important insights into the molecular mechanism of AUD and potential target genes for AUD treatment.

A Convergent Study of Genetic Variants Associated With Crohn's Disease: Evidence From GWAS, Gene Expression, Methylation, eQTL and TWAS.

Crohn's Disease (CD) is one of the predominant forms of inflammatory bowel disease (IBD). A combination of genetic and non-genetic risk factors have been reported to contribute to the development of CD. Many high-throughput omics studies have been conducted to identify disease associated risk variants that might contribute to CD, such as genome-wide association studies (GWAS) and next generation sequencing studies. A pressing need remains to prioritize and characterize candidate genes that underlie the etiology of CD. In this study, we collected a comprehensive multi-dimensional data from GWAS, gene expression, and methylation studies and generated transcriptome-wide association study (TWAS) data to further interpret the GWAS association results. We applied our previously developed method called mega-analysis of Odds Ratio (MegaOR) to prioritize CD candidate genes (CDgenes). As a result, we identified consensus sets of CDgenes (62-235 genes) based on the evidence matrix. We demonstrated that these CDgenes were significantly more frequently interact with each other than randomly expected. Functional annotation of these genes highlighted critical immune-related processes such as immune response, MHC class II receptor activity, and immunological disorders. In particular, the constitutive photomorphogenesis 9 (COP9) signalosome related genes were found to be significantly enriched in CDgenes, implying a potential role of COP9 signalosome involved in the pathogenesis of CD. Finally, we found some of the CDgenes shared biological functions with known drug targets of CD, such as the regulation of inflammatory response and the leukocyte adhesion to vascular endothelial cell. In summary, we identified highly confident CDgenes from multi-dimensional evidence, providing insights for the understanding of CD etiology.

A first integrative study of the identity and origins of the British Dwarf Pill Millipede populations, Trachysphaera cf. lobata (Diplopoda, Glomerida, Glomeridae).

Three populations of the pill millipede genus Trachysphaera Heller 1858 are present in Great Britain, one on the Isle of Wight, one in South Wales and one in mid-Wales. To identify and characterize the British Trachysphaera populations, the intraspecific and interspecific variation of the populations in South Wales and on the Isle of Wight were studied and evaluated in a first integrative study of members of Trachysphaera, utilizing barcoding and SEM. DNA was extracted from 28 British Trachysphaera and 10 French T. lobata (Ribaut 1954) specimens, one each of French T. cf. drescoi (Conde and Demange 1961) and T. pyrenaica (Ribaut 1908), and one of Spanish T. cf. rousseti (Demange 1959); the barcoding fragment of the COI gene was amplified and their genetic intra- and interpopulation distances compared with one another using two Italian T. spp. and one Croatian T. schmidti Heller 1858 specimens as near outgroups. To compare the genetic distances with the morphological characters, 15 characters of a total of 13 British Trachysphaera, together with two specimens of T.pyrenaica, two T. cf. drescoi and one of T. cf. rousseti were imaged, using the same individuals utilized for DNA extraction. Albeit both British populations are genetically distant, they are closely related (1.9-2.5% p-distance) to French T.lobata, corroborating results of earlier studies. Between different Trachysphaera species, genetic distance was high (16.7-18.8%). The morphological study showed the non-reliability of key taxonomic characters in Trachysphaera, with genetically identical individuals exhibiting morphological variation, especially on the telopods. The only observed morphological characters constant within and different between species were the number of rows of sclerotized bacilli on the tergites, as well as the shape of the male and female anal shield. Both, barcoding and the morphological study identify the British Trachysphaera populations as T. lobata.