Homoeologous exchanges cause extensive dosage-dependent gene expression changes in an allopolyploid crop.

Structural variation is a major source of genetic diversity and an important substrate for selection. In allopolyploids, homoeologous exchanges (i.e. between the constituent subgenomes) are a very frequent type of structural variant. However, their direct impact on gene content and gene expression had not been determined. Here, we used a tissue-specific mRNA-Seq dataset to measure the consequences of homoeologous exchanges (HE) on gene expression in Brassica napus, a representative allotetraploid crop. We demonstrate that expression changes are proportional to the change in gene copy number triggered by the HEs. Thus, when homoeologous gene pairs have unbalanced transcriptional contributions before the HE, duplication of one copy does not accurately compensate for loss of the other and combined homoeologue expression also changes. These effects are, however, mitigated over time. This study sheds light on the origins, timing and functional consequences of homeologous exchanges in allopolyploids. It demonstrates that the interplay between new structural variation and the resulting impacts on gene expression, influences allopolyploid genome evolution.

Identification and isolation of a Fel d 1-like molecule as a major rabbit allergen.

BACKGROUND: Rabbits are increasingly kept as domestic pets. Several rabbit allergens have been characterized. However, their sequences are still elusive, and none of these molecules are available for diagnosis. OBJECTIVE: We sought to isolate major allergens from the rabbit Oryctolagus cuniculus and to investigate their importance in sensitized patients. METHODS: Proteins were extracted from rabbit hair, and IgE-reactive proteins were purified by using sequential chromatography. Allergens were characterized by means of N-terminal sequencing and mass spectrometry. IgE reactivity to a new allergen was analyzed in sera of 35 patients sensitized to rabbits in a domestic setting. A model of the crystal structure of the isolated proteins was constructed. RESULTS: A new IgE-reactive allergen, Ory c 3, was identified as rabbit lipophilin. The molecule that belongs to the secretoglobin family is a heterodimer of 18 to 19 kDa composed of 2 polypeptide chains, CL2 and AL. CL2 has a predicted N-linked glycosylation site confirmed by using mass spectrometry. Of the 35 patients with rabbit allergy studied, 27 (77%) had IgE to both the glycosylated and deglycosylated Ory c 3 heterodimer. Allergenicity of Ory c 3 was confirmed by using skin prick tests and the basophil activation assay. Modeling of the structure revealed a marked homology to Fel d 1, the major cat allergen. However, no IgE cross-reactivity was detected between Fel d 1 and Ory c 3. CONCLUSION: The rabbit lipophilin heterodimer AL-CL2 has been identified as a major rabbit allergen. After Fel d 1, Ory c 3 is the second mammalian secretoglobin shown to be a major allergen.

Corrigendum: FANCM Limits Meiotic Crossovers in Brassica Crops.

[This corrects the article DOI: 10.3389/fpls.2018.00368.].

Development of a concise QOL questionnaire for brain tumor patients.

BACKGROUND: The purpose of this study was to develop and validate a self-administered questionnaire to measure the health-related quality of life (QOL) of patients with brain cancer. We wanted to assess both core and disease-specific concerns in a single, easy-to-use instrument, thus promoting concision and clinical utility. The questionnaire departs from its predecessors in that it was designed for- and validated among French speaking Canadians. METHODS: A focus group of health professionals was used to develop items for the questionnaire, which was later validated with 105 patients suffering from brain cancer. The underlying structure of the questionnaire was investigated using principal component analysis and confirmed using a principal factor analysis. RESULTS: The final version of the questionnaire contains 30 items. Seven multi-item scales, tapping into distinct dimensions of QOL, were uncovered (i.e., functional well-being, symptom severity/fear of death, social support/acceptance of disease, autonomy in personal care, digestive symptomatology, neurocognitive function, and pain). Assessment of reliability revealed elevated internal consistency for each of the seven scales (Cronbach coefficient alpha .65), whereas known-groups validity (anchor-based approach) revealed that the different dimensions uniquely discriminated between patients with different functional levels (Karnofsky Performance Scores) and clinical status (exposure to neurosurgery, radiotherapy, and use of chemotherapy and anticonvulsants). CONCLUSION: Our QOL questionnaire, the Sherbrooke Neuro-Oncology Assessment Scale, or SNAS, taps into both core and disease-specific issues relevant to neuro-oncology patients. It has good validity and reliability, and clearly reflects the multidimensional nature of QOL. Depending on the research focus, it may be used in clinical trials to track the impact of disease and/or treatment on satisfaction, functional status, and general well-being.

Systemic versus Pulmonary Bleeding in Lung Infection: Value of CT in Two Cases.

Bronchial and pulmonary artery aneurysms are rare causes of hemoptysis in the course of lung infection, for which early diagnosis and treatment are essential to prevent fatal bleeding. Depending on patient condition, these occurrences are amenable to computed tomography (CT) to determine both the cause of hemoptysis and the bleeding site in order to plan the most effective bleeding-control procedure. In this report, we illustrate the importance of the bleeding site identification using CT in two cases of infection-related hemoptysis.

Reducing MSH4 copy number prevents meiotic crossovers between non-homologous chromosomes in Brassica napus.

In allopolyploids, correct chromosome segregation requires suppression of non-homologous crossovers while levels of homologous crossovers are ensured. To date, no mechanism able to specifically inhibit non-homologous crossovers has been described in allopolyploids other than in bread wheat. Here, we show that reducing the number of functional copies of MSH4, an essential gene for the main crossover pathway, prevents non-homologous crossovers in allotetraploid Brassica napus. We show that non-homologous crossovers originate almost exclusively from the MSH4-dependent recombination pathway and that their numbers decrease when MSH4 returns to single copy in B. napus; by contrast, homologous crossovers remain unaffected by MSH4 duplicate loss. We also demonstrate that MSH4 systematically returns to single copy following numerous independent polyploidy events, a pattern that is probably not by chance. These results suggest that stabilization of allopolyploid meiosis can be enhanced by loss of a key meiotic recombination gene.

FANCM Limits Meiotic Crossovers in Brassica Crops.

Meiotic crossovers (COs) are essential for proper chromosome segregation and the reshuffling of alleles during meiosis. In WT plants, the number of COs is usually small, which limits the genetic variation that can be captured by plant breeding programs. Part of this limitation is imposed by proteins like FANCM, the inactivation of which results in a 3-fold increase in COs in Arabidopsis thaliana. Whether the same holds true in crops needed to be established. In this study, we identified EMS induced mutations in FANCM in two species of economic relevance within the genus Brassica. We showed that CO frequencies were increased in fancm mutants in both diploid and tetraploid Brassicas, Brassica rapa and Brassica napus respectively. In B. rapa, we observed a 3-fold increase in the number of COs, equal to the increase observed previously in Arabidopsis. In B. napus we observed a lesser but consistent increase (1.3-fold) in both euploid (AACC) and allohaploid (AC) plants. Complementation tests in A. thaliana suggest that the smaller increase in crossover frequency observed in B. napus reflects residual activity of the mutant C copy of FANCM. Altogether our results indicate that the anti-CO activity of FANCM is conserved across the Brassica, opening new avenues to make a wider range of genetic diversity accessible to crop improvement.