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941.
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943.
Potential of a tomato MAGIC population to decipher the genetic control of quantitative traits and detect causal variants in the resequencing era 下载免费PDF全文
Laura Pascual Nelly Desplat Bevan E. Huang Aurore Desgroux Laure Bruguier Jean‐Paul Bouchet Quang H. Le Betty Chauchard Philippe Verschave Mathilde Causse 《Plant biotechnology journal》2015,13(4):565-577
Identification of the polymorphisms controlling quantitative traits remains a challenge for plant geneticists. Multiparent advanced generation intercross (MAGIC) populations offer an alternative to traditional linkage or association mapping populations by increasing the precision of quantitative trait loci (QTL) mapping. Here, we present the first tomato MAGIC population and highlight its potential for the valorization of intraspecific variation, QTL mapping and causal polymorphism identification. The population was developed by crossing eight founder lines, selected to include a wide range of genetic diversity, whose genomes have been previously resequenced. We selected 1536 SNPs among the 4 million available to enhance haplotype prediction and recombination detection in the population. The linkage map obtained showed an 87% increase in recombination frequencies compared to biparental populations. The prediction of the haplotype origin was possible for 89% of the MAGIC line genomes, allowing QTL detection at the haplotype level. We grew the population in two greenhouse trials and detected QTLs for fruit weight. We mapped three stable QTLs and six specific of a location. Finally, we showed the potential of the MAGIC population when coupled with whole genome sequencing of founder lines to detect candidate SNPs underlying the QTLs. For a previously cloned QTL on chromosome 3, we used the predicted allelic effect of each founder and their genome sequences to select putative causal polymorphisms in the supporting interval. The number of candidate polymorphisms was reduced from 12 284 (in 800 genes) to 96 (in 54 genes), including the actual causal polymorphism. This population represents a new permanent resource for the tomato genetics community. 相似文献
944.
Samuel C. B. Stubbs Edison Johar Frilasita A. Yudhaputri Benediktus Yohan Marsha S. Santoso Rahma F. Hayati Dionisius Denis Barbara A. Blacklaws Ann M. Powers R. Tedjo Sasmono Khin Saw Aye Myint Simon D. W. Frost 《PLoS neglected tropical diseases》2020,14(12)
BackgroundChikungunya virus (CHIKV) is an important emerging and re-emerging public health problem worldwide. In Indonesia, where the virus is endemic, epidemiological information from outside of the main islands of Java and Bali is limited.Methodology/Principal FindingsFour hundred and seventy nine acutely febrile patients presenting between September 2017–2019 were recruited from three city hospitals situated in Ambon, Maluku; Banjarmasin, Kalimantan; and Batam, Batam Island as part of a multi-site observational study. CHIKV RNA was detected in a single serum sample while a separate sample was IgM positive. IgG seroprevalence was also low across all three sites, ranging from 1.4–3.2%. The single RT-PCR positive sample from this study and 24 archived samples collected during other recent outbreaks throughout Indonesia were subjected to complete coding region sequencing to assess the genetic diversity of Indonesian strains. Phylogenetic analysis revealed all to be of a single clade, which was distinct from CHIKV strains recently reported from neighbouring regions including the Philippines and the Pacific Islands.Conclusions/SignificanceChikungunya virus strains from recent outbreaks across Indonesia all belong to a single clade. However, low-level seroprevalence and molecular detection of CHIKV across the three study sites appears to contrast with the generally high seroprevalences that have been reported for non-outbreak settings in Java and Bali, and may account for the relative lack of CHIKV epidemiological data from other regions of Indonesia. 相似文献
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946.
Mackay M Bussa MP Aranow C Uluğ AM Volpe BT Huerta PT Argyelan M Mandel A Hirsch J Diamond B Eidelberg D 《Molecular medicine (Cambridge, Mass.)》2011,17(11-12):1349-1356
The mediators of tissue damage in systemic lupus erythematosus (SLE) such as antibodies, cytokines and activated immune cells have direct access to most organs in the body but must penetrate the blood-brain barrier (BBB) to gain access to brain tissue. We hypothesized that compromise of the BBB occurs episodically such that the brain will acquire tissue damage slowly and not at the same rate as other organs. On the basis of these assumptions, we wished to determine if duration of disease correlated with brain injury, as measured with functional magnetic resonance imaging (fMRI), and if this was independent of degree of tissue damage in other organs. We investigated differences in brain activation patterns using fMRI in 13 SLE patients stratified by disease duration of ≤2 years (short-term [ST]) or ≥10 years (long-term [LT]). Two fMRI paradigms were selected to measure working memory and emotional response (fearful faces task). Performance in the working memory task was significantly better in the ST group for one and two shape recall; however, both groups did poorly with three shape recall. Imaging studies demonstrated significantly increased cortical activation in the ST group in regions associated with cognition during the two shape retention phase of the working memory task (P < 0.001) and increased amygdala (P < 0.05) and superior parietal (P < 0.01) activation in response to the fearful faces paradigm. In conclusion, analysis of activation patterns stratified by performance accuracy, differences in co-morbid disease, corticosteroid doses or disease activity suggests that these observed differences are attributable to SLE effects on the central nervous system exclusive of vascular disease or other confounding influences. Our hypothesis is further supported by the lack of correlation between regional brain abnormalities on fMRI and the Systemic Lupus International Collaborating Clinics (SLICC) damage index. 相似文献
947.
Hill L Jeganathan V Chinnasamy P Grimaldi C Diamond B 《Molecular medicine (Cambridge, Mass.)》2011,17(3-4):211-220
It is clear that estrogen can accelerate and exacerbate disease in some lupus-prone mouse strains. It also appears that estrogen can contribute to disease onset or flare in a subset of patients with lupus. We have previously shown estrogen alters B-cell development to decrease lymphopoiesis and increase the frequency of marginal zone B cells. Furthermore, estrogen diminishes B-cell receptor signaling and allows for the increased survival of high-affinity DNA-reactive B cells. Here, we analyze the contribution of estrogen receptor α or β engagement to the altered B-cell maturation and selection mediated by increased exposure to estrogen. We demonstrate that engagement of either estrogen receptor α or β can alter B-cell maturation, but only engagement of estrogen receptor α is a trigger for autoimmunity. Thus, maturation and selection are regulated differentially by estrogen. These observations have therapeutic implications. 相似文献
948.
Ichikawa M Bawn S Maw NN Htun LL Thein M Gyi A Sunn K Katakura K Itagaki T 《Parasitology international》2011,60(4):474-479
Fasciola spp. in Myanmar were characterized on the basis of spermatogenesis status and DNA markers of nuclear internal transcribed spacer 1 (ITS1) and mitochondrial NADH dehydrogenase subunit 1 (nad1). We collected 88 adult flukes from Yangon, Lashio, and Myitkyina. Spermatogenesis status was analyzed by the presence of sperm in the seminal vesicles, and 8 aspermic and 80 spermic flukes were detected. The flukes were identified on the basis of spermatogenesis status and ITS1 types which were analyzed by a PCR-RFLP method, and 80 spermic flukes were identified as F. gigantica. A very low detection rate of aspermic Fasciola sp. indicated that they are not established in Myanmar. In phylogenetic analyses, the 7 aspermic Fasciola sp. from Myitkyina displayed a haplotype in nad1 sequence, which was identical to that of aspermic Fasciola sp. from other Asian countries including China. Therefore, they were probably introduced from China through an infected domestic ruminant. On the other hand, 17 nad1 haplotypes detected in F. gigantica belonged to 2 clades unique to Myanmar, each with a distinct founder haplotype in a network analysis. This indicated a unique history of F. gigantica introduction into Myanmar involving ancient artificial movements of domestic ruminants. 相似文献
949.
Giang Ho TT Stultiens A Dubail J Lapière CM Nusgens BV Colige AC Deroanne CF 《Molecular biology of the cell》2011,22(17):3263-3275
RhoGTPases are key signaling molecules regulating main cellular functions such as migration, proliferation, survival, and gene expression through interactions with various effectors. Within the RhoA-related subclass, RhoA and RhoC contribute to several steps of tumor growth, and the regulation of their expression affects cancer progression. Our aim is to investigate their respective contributions to the acquisition of an invasive phenotype by using models of reduced or forced expression. The silencing of RhoC, but not of RhoA, increased the expression of genes encoding tumor suppressors, such as nonsteroidal anti-inflammatory drug-activated gene 1 (NAG-1), and decreased migration and the anchorage-independent growth in vitro. In vivo, RhoC small interfering RNA (siRhoC) impaired tumor growth. Of interest, the simultaneous knockdown of RhoC and NAG-1 repressed most of the siRhoC-related effects, demonstrating the central role of NAG-1. In addition of being induced by RhoC silencing, NAG-1 was also largely up-regulated in cells overexpressing RhoA. The silencing of RhoGDP dissociation inhibitor α (RhoGDIα) and the overexpression of a RhoA mutant unable to bind RhoGDIα suggested that the effect of RhoC silencing is indirect and results from the up-regulation of the RhoA level through competition for RhoGDIα. This study demonstrates the dynamic balance inside the RhoGTPase network and illustrates its biological relevance in cancer progression. 相似文献
950.
Lee K Kunkeaw N Jeon SH Lee I Johnson BH Kang GY Bang JY Park HS Leelayuwat C Lee YS 《RNA (New York, N.Y.)》2011,17(6):1076-1089
Noncoding RNAs have drawn significant attention in biology recently. Whereas the current research is highly inclined to microRNAs, research on other noncoding RNAs has lagged behind. Here, we investigated a novel noncoding RNA that has been known as precursor microRNA miR-886 (pre-miR-886). Pre-miR-886 has been proposed also as a vault RNA, a component of the vault complex implicated in cancer drug resistance. We identified pre-miR-886 as a 102-nucleotide-long, abundant cytoplasmic RNA that is neither a genuine pre-microRNA nor a vault RNA. Pre-miR-886 is physically associated with PKR (Protein Kinase RNA-activated), an interferon-inducible and double-stranded RNA dependent kinase. The suppression of pre-miR-886 activates PKR and its downstream pathways, eIF2α phosphorylation and the NF-κB pathway, leading to impaired cell proliferation. We also found that pre-miR-886 is suppressed in a wide-range of cancer cell lines and in clinical specimens. This study is the first intense characterization of pre-miR-886 as well as the initial report on its function as a PKR regulator, which suggests a critical role in tumorigenesis. 相似文献