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糖尿病肾病遗传学研究进展 总被引:6,自引:0,他引:6
糖尿病肾病是糖尿病最严重的慢性并发症之一, 不同种族的发病率分析和家族聚集性研究显示遗传因素是糖尿病肾病发生、发展的重要因素。文章从3个方面对糖尿病肾病的遗传学研究进展进行综述:“候选基因”的关联研究、连锁分析和全基因组关联研究。关联研究及荟萃分析显示一些候选基因与糖尿病肾病显著相关, 包括ACE、AGT和PPARG等基因; 连锁分析及全基因组连锁分析发现多个糖尿病肾病的易感染色体位点; 随着高通量测序技术和芯片技术的发展, 全基因组关联研究已成为糖尿病肾病遗传学研究的重要途径。虽然遗传因素在糖尿病肾病发病中占据重要的位置, 但还不能完全解释糖尿病肾病的发病原因, 因为糖尿病肾病的发生还受环境因素的影响, 然而糖尿病肾病的遗传学研究可为糖尿病肾病发病机制研究以及药物治疗靶点研究提供一定的理论依据。 相似文献
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Parkin and the molecular pathways of Parkinson's disease 总被引:10,自引:0,他引:10
Parkinson's disease (PD) is a neurodegenerative disease characterized by the selective demise of specific neuronal populations leading to impairment of motor functions. Recent genetic studies have uncovered several genes involved in inherited forms of the disease. These gene products are implicated in the biochemical pathways underlying the etiology of sporadic PD. Mutations in the parkin gene causal of autosomal recessive juvenile parkinsonism highlight that ubiquitin-mediated proteolysis may play an important role in the pathobiology of PD. 相似文献
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Pabst S Hammerstingl C Hundt F Gerhardt T Grohé C Nickenig G Woitas R Skowasch D 《PloS one》2012,7(4):e35310
Pulmonary hypertension (PH) is common in patients with dialysis-dependent chronic kidney disease and is an independent predictor of mortality. However, specific hemodynamics of the pulmonary circulation, changes induced by hemodialysis and characterization into pre- or postcapillary PH have not been evaluated in patients with chronic kidney disease. We assessed consecutive patients with end-stage chronic kidney disease in WHO FC ≥ II with dyspnea unexplained by other causes on hemodialysis (group 1, n = 31) or without dialysis (group 2, n = 31) using right heart catheterization (RHC). In group 1, RHC was performed before and after dialysis. In end-stage chronic kidney disease, prevalence of precapillary PH was 13% (4/31), and postcapillary PH was discovered in 65% (20/31). All four cases of precapillary PH were unmasked after dialysis. In group 2, two cases of precapillary PH were detected (6%), and postcapillary PH was diagnosed in 22 cases (71%). This is the first study examining a large cohort of patients with chronic kidney disease invasively by RHC for the prevalence of PH. The prevalence of precapillary PH was 13% in patients with end-stage kidney disease. That suggests careful screening for precapillary PH in this selected patient population. RHC should be performed after hemodialysis. 相似文献
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Zhilian Li Xinling Liang Shuangxin Liu Zhiming Ye Yuanhan Chen Wenjian Wang Ruizhao Li Lixia Xu Zhonglin Feng Wei Shi 《PloS one》2014,9(12)
BackgroundPulmonary hypertension (PH) was recently recognized as a common complication of end-stage renal disease (ESRD) that causes an increased risk of mortality. Epidemiological data for this disorder in earlier stages of chronic kidney disease (CKD) and its association with cardiovascular (CV) morbidity are scarce.MethodsWe retrospectively analyzed 2,351 Chinese CKD patients with complete clinical records and echocardiography data between Jan 2008 and May 2012. The patients were divided into the following 6 groups: CKD Stages 1–4; Stage 5 for those not on or initiated on hemodialysis for <3 months; and Stage 5D for the patients undergoing hemodialysis for ≥3 months. The prevalence of PH and CV morbidity was investigated, and their association was evaluated with a logistic regression model.ResultsPH was detected in 426 patients (18.1%). Mild, moderate and severe PH was diagnosed in 12.1%, 4.9% and 1.1% of the patients, respectively. Severe PH was detected in CKD Stages 5 and 5D. CV morbidity was found in 645 patients (27.4%). Compared with the non-PH group, the PH group had a higher risk for cardiac disease but not for cerebrovascular disease risk. PH severity was associated with cardiac morbidity risk [odds ratio (95% CI) for mild PH: 1.79 (1.30–2.47); moderate PH: 2.75 (1.73–4.37); severe PH: 3.90 (1.46–10.42)].ConclusionsOur study showed for the first time the epidemiology profile of PH across the spectrum of CKD. Mild-to-moderate PH occurs with more frequency in advanced CKD, and severe PH is scarce in non-ESRD CKD. PH in CKD is associated with cardiac but not cerebrovascular disease, with increasing cardiac morbidity seen with increasing PH severity. Evidence from prospective studies addressing PH in this population is needed to predict cardiac events. 相似文献
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Manuel Jonas Richter Svenja Lena Tiede Natascha Sommer Thomas Schmidt Werner Seeger Hossein Ardeschir Ghofrani Ralph Schermuly Henning Gall 《PloS one》2016,11(11)
BackgroundCirculating angiopoietin-1 (Ang-1) has been linked to pulmonary hypertension (PH) in experimental studies. However, the clinical relevance of Ang-1 as a biomarker in PH remains unknown. We aimed to investigate the prognostic and clinical significance of Ang-1 in PH using data from the prospectively recruiting Giessen PH Registry.MethodsPatients with suspected PH (without previous specific pulmonary arterial hypertension [PAH] therapy) who underwent initial right heart catheterization (RHC) in our national referral center between July 2003 and May 2012 and who agreed to optional biomarker analysis were included if they were diagnosed with idiopathic PAH, connective tissue disease-associated PAH (CTD-PAH), PH due to left heart disease (PH-LHD), or chronic thromboembolic PH (CTEPH), or if PH was excluded by RHC (non-PH controls). The association of Ang-1 levels with disease severity (6-minute walk distance and pulmonary hemodynamics) was assessed using linear regression, and the impact of Ang-1 levels on transplant-free survival (primary endpoint) and clinical worsening was assessed using Kaplan—Meier curves, receiver operating characteristic (ROC) analyses, and Cox regression.Results151 patients (39, 39, 32, and 41 with idiopathic PAH, CTD-PAH, PH-LHD, and CTEPH, respectively) and 41 non-PH controls were included. Ang-1 levels showed no significant difference between groups (p = 0.8), and no significant associations with disease severity in PH subgroups (p ≥ 0.07). In Kaplan—Meier analyses, Ang-1 levels (stratified by quartile) had no significant impact on transplant-free survival (p ≥ 0.27) or clinical worsening (p ≥ 0.51) in PH subgroups. Regression models found no significant association between Ang-1 levels and outcomes (p ≥ 0.31). ROC analyses found no significant cut-off that would maximize sensitivity and specificity.ConclusionsDespite a strong pathophysiological association in experimental studies, this first comprehensive analysis of Ang-1 in PH subgroups suggests that Ang-1 is not a predictive and clinically relevant biomarker in PH. 相似文献
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Xu C Chang C Yuan J Han H Yang K Zhao L Li W Li Y Zhang H Rahman S Zhang J 《基因组蛋白质组与生物信息学报(英文版)》2004,2(2):109-118
The mammalian liver has a very strong regeneration capacity after partial hepatectomy (PH). To further learn the genes participating in the liver regeneration (LR), 551 cDNAs selected from subtracted cDNA libraries of the regenerating rat liver were screened by microarray, and their expression profiles were studied by cluster and generalization analyses. Among them, 177 genes were identified unreported and up-or down-regulated more than twofold at one or more time points after PH, of which 62 genes were down-regulated to less than 0.5; 99 genes were up-regulated to 2-10 folds, and 16 genes were either up- or down-regulated at different time points during LR. By using BLAST and GENSCAN, these genes were located on responsible chromosomes with 131 genes on the long arms of the chromosomes. The cluster and generalization analyses showed that the gene expression profiles are similar in 2 and 4, 12 and 16, 96 and 144 h respectively after PH, suggesting that the actions of the genes expressed in the same profiles are similar, and those expressed in different profiles have less similarity. However, the types,characteristics and functions of the 177 genes remain to be further studied. 相似文献
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Jing Liu Bo Feng Zhibin Xu Xiaoli Fan Fei Jiang Xiufeng Jin Jun Cao Fang Wang Qin Liu Li Yang Tao Wang 《Molecular breeding : new strategies in plant improvement》2018,38(1):1
Wheat (Triticum aestivum L.) is one of the most productive and important crops and its yield potential and quality characteristics are tightly linked with the global food security. In this study, genome-wide association study (GWAS) was conducted for yield and quality-related traits. Based on the high-density wheat 90K Illumina iSelect SNP Array, 192 bread wheat lines from southwest China, including 25 synthetic hexaploid wheat lines, 80 landraces, and 87 cultivars were analyzed. Association analysis results indicated that there were 57, 27, 30, and 34 SNPs associated with plant height (PH), grain protein content (GPC), thousand kernel weight (TKW), and SDS sedimentation volume (SSV) have been detected, respectively. Then, integrating RNA-Seq with bioinformatics analysis, 246 candidate genes (102 for GPC, 52 for TKW, and 92 for SSV) were found. Further analysis indicated that one up-regulated and two down-regulated expression genes affect GPC. Additionally, two haplotypes significantly affecting PH were detected in a 2.2-Mb genome region encompassing a gene which encoded an ubiquitin-specific protease, TaUBP24. The functional markers of TaUBP24 have been developed, which could be used for marker-assisted selection to improve wheat quality and yield. 相似文献
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Linkage disequilibrium patterns vary with chromosomal location: a case study from the von Willebrand factor region. 总被引:9,自引:6,他引:3
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W. S. Watkins R. Zenger E. O'Brien D. Nyman A. W. Eriksson M. Renlund L. B. Jorde 《American journal of human genetics》1994,55(2):348-355
Linkage disequilibrium analysis has been used as a tool for analyzing marker order and locating disease genes. Under appropriate circumstances, disequilibrium patterns reflect recombination events that have occurred throughout a population's history. As a result, disequilibrium mapping may be useful in genomic regions of < 1 cM where the number of informative meioses needed to detect recombinant individuals within pedigrees is exceptionally high. Its utility for refining target areas for candidate disease genes before initiating chromosomal walks and cloning experiments will be enhanced as the relationship between linkage disequilibrium and physical distance is better understood. To address this issue, we have characterized linkage disequilibrium in a 144-kb region of the von Willebrand factor gene on chromosome 12. Sixty CEPH and 12 von Willebrand disease families were genotyped for five PCR-based markers, which include two microsatellite repeats and three single-base-pair substitutions. Linkage disequilibrium and physical distance between polymorphisms are highly correlated (rm = -.76; P < .05) within this region. None of the five markers showed significant disequilibrium with the von Willebrand disease phenotype. The linkage disequilibrium/physical distance relationship was also analyzed as a function of chromosomal location for this and eight previously characterized regions. This analysis revealed a general trend in which linkage disequilibrium dissipates more rapidly with physical distance in telomeric regions than in centromeric regions. This trend is consistent with higher recombination rates near telomeres. 相似文献
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Marjolein Lisette den Toom Guy Grinwis Robert-Jan van Suylen Susanne Adetokunbo Boroffka Pim de Jong Frank Geurt van Steenbeek Viktor Szatmári 《Acta veterinaria Scandinavica》2018,60(1):78
Background
Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary arterial hypertension (PAH) in humans and can be classified in idiopathic, heritable, drug and radiation-induced, and associated with connective tissue disease or human immunodeficiency virus infection. Recently, biallelic mutations of the EIF2AK4 gene have been discovered as a cause for an autosomal recessive form of PVOD in humans. In dogs, PAH is poorly characterized and is generally considered to be idiopathic or secondary to (for example) congenital left-to right cardiovascular shunts or heartworm disease. However, recently, the pathologic features resembling human PVOD were retrospectively described in post-mortem lung samples of dogs presenting with respiratory distress and idiopathic pulmonary hypertension (PH), which suggests that PVOD contributes to an unknown percentage of cases with unexplained PH. In dogs, information on the clinical presentation of PVOD is scarce and the cause and pathogenesis of this disease is still unknown.Case presentation
An 11-year-old, intact male German Shepherd dog (GSD) was presented with a 2-day history of acute-onset dyspnea and generalized weakness. Physical examination, laboratory analysis, thoracic radiography, echocardiography, a computed tomography scan and an ante mortem lung biopsy demonstrated severe arterial hypoxemia and severe PH but were not diagnostic for a known disease syndrome. Based on the poor reaction to therapy with oxygen, sildenafil, pimobendan and dexamethasone the dog was euthanized. Histopathology of the lungs showed venous and arterial remodelling, segmental congestion of alveolar capillaries and foci of vascular changes similar to human pulmonary capillary hemangiomatosis, indicating that the dog suffered from PVOD. Whole genome sequencing analysis was performed on the case and a healthy GSD. Validation was performed by Sanger sequencing of five additional GSD's unknown for any form of respiratory stress and aged ≥?10 years. No causal variants were found in the genes that are known to be involved in human PVOD and PAH.Conclusions
This case report confirms that PVOD should be a diagnostic consideration in dogs presenting with dyspnea and unexplained PH. In the present case, no casual genetic mutations known to be involved in humans with PVOD and PAH were found.15.
Extensive gene expression analysis was carried out after a 0, 4, 36, 72, 96 h short interval successive partial hepatectomy
(SISPH) was performed. A total of 185 elements were identified as differing by more than two-fold in their expression levels
at one or more time points. Of these 185 elements, 103 were up-regulated, 82 were down-regulated and 86 elements were unreported
genes. Quite a few genes were previously unknown to be involved in liver regeneration (LR). Using cluster and general analysis,
we found that the genes at five time points of the SISPH share eight different types of different expression profiles and
eight distinct temporal induction or suppression patterns. A comparison of the gene expression in SISPH with that after PH
found that 41 genes were specifically altered in SISPH, and 144 genes were simultaneously up-regulated or down-regulated in
SISPH and after PH, but they were present in different amounts at the different time points. The conclusions are that (i)
microarrays combined with suppressive subtractive hybridization (SSH) can effectively identify genes involved in LR on a large
scale; (ii) more genes were up-regulated than down-regulated; (iii) there are fewer abundantly expressed genes than those
with increased levels of 2–5 fold. 相似文献
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Lin Chen Yong-xiang Li Chunhui Li Yunsu Shi Yanchun Song Dengfeng Zhang Yu Li Tianyu Wang 《BMC plant biology》2018,18(1):366
Background
The pentatricopeptide repeat (PPR) gene family is one of the largest gene families in land plants (450 PPR genes in Arabidopsis, 477 PPR genes in rice and 486 PPR genes in foxtail millet) and is important for plant development and growth. Most PPR genes are encoded by plastid and mitochondrial genomes, and the gene products regulate the expression of the related genes in higher plants. However, the functions remain largely unknown, and systematic analysis and comparison of the PPR gene family in different maize genomes have not been performed.Results
In this study, systematic identification and comparison of PPR genes from two elite maize inbred lines, B73 and PH207, were performed. A total of 491 and 456 PPR genes were identified in the B73 and PH207 genomes, respectively. Basic bioinformatics analyses, including of the classification, gene structure, chromosomal location and conserved motifs, were conducted. Examination of PPR gene duplication showed that 12 and 15 segmental duplication gene pairs exist in the B73 and PH207 genomes, respectively, with eight duplication events being shared between the two genomes. Expression analysis suggested that 53 PPR genes exhibit qualitative variations in the different genetic backgrounds. Based on analysis of the correlation between PPR gene expression in kernels and kernel-related traits, four PPR genes are significantly negatively correlated with hundred kernel weight, 12 are significantly negatively correlated with kernel width, and eight are significantly correlated with kernel number. Eight of the 24 PPR genes are also located in metaQTL regions associated with yield and kernel-related traits in maize. Two important PPR genes (GRMZM2G353195 and GRMZM2G141202) might be regarded as important candidate genes associated with maize kernel-related traits.Conclusions
Our results provide a more comprehensive understanding of PPR genes in different maize inbred lines and identify important candidate genes related to kernel development for subsequent functional validation in maize.17.
RAHMAN Salman 《中国科学:生命科学英文版》2005,48(6):624-635
After partial hepatectomy (PH), the remnant paren-chyma can completely recover lost liver mass and function in about one week[1,2]. Although adult hepa-tocytes are normally quiescent, they are readily primed to pass from G0 to G1 phase within 2―6 h after PH. The first peak of DNA synthesis appears 24 h after PH, while cell division peaks at 36 h. The liver cells then enter a second cell cycle, and redifferentiation and reconstruction of structure and function[3―6] take place. A great nu… 相似文献
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Jiaoping Zhang Qijian Song Perry B Cregan Randall L Nelson Xianzhi Wang Jixiang Wu Guo-Liang Jiang 《BMC genomics》2015,16(1)