genetic inheritance

遗传遗传
  • 文章类型: Journal Article
    神经发育是一个高度有组织和复杂的过程,涉及中枢神经系统的持久且通常不可逆的变化。遗传性神经传递障碍(IDNT)是一组遗传性疾病,其中神经传递主要受到影响,导致早期大脑发育异常,表现为神经发育障碍和其他慢性疾病。原则上,IDNT(特别是单基因原因的那些)适合通过精确的遗传校正进行基因替代疗法。然而,基因替代疗法的实际挑战仍然是其从长凳到床边翻译的主要障碍。我们讨论了IDNT基因替代疗法开发的关键考虑因素。作为一个例子,我们描述了我们正在进行的琥珀酸半醛脱氢酶缺乏症基因替代疗法的工作,GABA分解代谢紊乱.
    Neurodevelopment is a highly organized and complex process involving lasting and often irreversible changes in the central nervous system. Inherited disorders of neurotransmission (IDNT) are a group of genetic disorders where neurotransmission is primarily affected, resulting in abnormal brain development from early life, manifest as neurodevelopmental disorders and other chronic conditions. In principle, IDNT (particularly those of monogenic causes) are amenable to gene replacement therapy via precise genetic correction. However, practical challenges for gene replacement therapy remain major hurdles for its translation from bench to bedside. We discuss key considerations for the development of gene replacement therapies for IDNT. As an example, we describe our ongoing work on gene replacement therapy for succinic semialdehyde dehydrogenase deficiency, a GABA catabolic disorder.
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  • 文章类型: Journal Article
    目的:卵母细胞供体和受体如何看待与供体和后代之间核DNA转移相关的遗传联系?
    结论:无论他们是供体还是受体,个人非常重视遗传遗产的传播,因为94.5%的人会选择原核转移方法,以在卵母细胞捐赠的背景下保留这种遗传联系。
    背景:自1983年以来,卵母细胞捐赠的使用在世界范围内有所增加。自1980年代后期以来在法国演出,最初提供给卵巢早衰的女性,它的适应症已经逐步扩大,现在在许多适应症中提出了防止遗传遗传疾病的传播。由于法国ART中心难以招募卵母细胞捐献者,这导致获得卵母细胞捐献的等待时间增加。几篇文章讨论了如何公平地将供体卵母细胞分配给夫妇,但是很少有人采访普通人群中的女性来记录她们对卵母细胞捐赠的感受,作为捐赠者或接受者,以及卵母细胞捐赠者和出生孩子之间遗传联系的重要性。线粒体替代疗法(MRT)是一种最初为有传播线粒体DNA突变风险的女性开发的技术。最近,MRT已被考虑用于胚胎停滞和卵母细胞再生,因为它可以通过将卵母细胞核转移到健康的供体卵母细胞细胞质中来帮助雌性繁殖自己的遗传物质。
    方法:我们于2021年1月至2021年12月进行了意见调查,在此期间,1956名妇女完成了问卷。由于对所有问题的回答不完整,13名参与者被排除在分析之外。因此,1943年妇女被纳入研究。
    方法:我们专门为这项研究开发了一份问卷,它是使用Drag\'nSurvey®软件创建和分发的。问卷由21个项目组成,并与使用白板动画软件创建的视频一起显示。目的是分析某些因素是否,比如年龄,教育水平,婚姻状况,儿童数量,使用ART怀孕,视频观看,以及有关卵母细胞捐献的知识,与对卵母细胞捐赠的感觉有关,通过使用单变量条件逻辑回归模型。这种统计方法还用于评估女性是否更倾向于考虑使用原核转移技术而不是整个卵母细胞捐赠。随后使用逻辑回归在多变量模型中测试在单变量分析中发现具有统计学意义的所有参数。
    结果:大多数女性担心捐赠卵母细胞的生物学遗传贡献(94.8%)。女性不愿意捐献卵母细胞的最常见原因是她们不愿意传递她们的遗传物质(33.3%)。最初不愿捐赠卵母细胞的妇女中有近70%表示,如果使用捐赠的细胞质和原核转移技术进行卵母细胞捐赠,她们将重新考虑自己的决定。同时,>75%的受访者提到接受细胞质捐赠会更容易。接受调查的人口比例最大(94.5%)表示支持其合法化。
    结论:在这项研究中,很大一部分反应来自有医学或辅助医学背景的个人,可能在潜在的捐赠者中引入招聘偏见。对有关成为卵母细胞供体的愿望的问题的缺失率为13.6%,而关于成为卵母细胞细胞质供体的问题有23%的缺失应答率。这些缺失的响应可能会在数据的解释中引入偏差。
    结论:这项研究首次证明,对于所研究的法国人口来说,卵母细胞胞质捐献与前核移植的结合可以提供一种有希望的方法,以提高供体和受体对卵母细胞捐献的接受度。
    背景:本研究未使用外部资金。作者没有利益冲突。
    背景:不适用。
    OBJECTIVE: How do oocyte donors and recipients perceive the genetic link related to the transfer of nuclear DNA between donors and offspring?
    CONCLUSIONS: Whether they are donors or recipients, individuals attach great importance to the transmission of their genetic heritage, since 94.5% would opt for the pronuclear transfer method to preserve this genetic link in the context of oocyte donation.
    BACKGROUND: Since 1983, the use of oocyte donation has increased worldwide. Performed in France since the late 1980s and initially offered to women with premature ovarian insufficiency, its indications have progressively expanded and now it is proposed in many indications to prevent the transmission of genetically inherited diseases. This has resulted in an increase in the waiting time for access to oocyte donation due to the difficulty in recruiting oocyte donors in French ART centres. Several articles have discussed how to fairly distribute donor oocytes to couples, but few have interviewed women in the general population to record their feelings about oocyte donation, as either the donor or recipient and the importance given to the genetic link between the oocyte donors and the children born. Mitochondrial replacement therapy (MRT) is a technique originally developed for women at risk of transmitting a mitochondrial DNA mutation. Recently, MRT has been considered for embryo arrest and oocyte rejuvenation as it could help females to reproduce with their own genetic material through the transfer of their oocyte nucleus into a healthy donor oocyte cytoplasm.
    METHODS: We conducted an opinion survey from January 2021 to December 2021, during which 1956 women completed the questionnaire. Thirteen participants were excluded from the analysis due to incomplete responses to all the questions. Consequently, 1943 women were included in the study.
    METHODS: We specifically developed a questionnaire for this study, which was created and distributed using the Drag\'n Survey® software. The questionnaire consisted of 21 items presented alongside a video created with whiteboard animation software. The aim was to analyse whether certain factors, such as age, education level, marital status, number of children, use of ART for pregnancy, video viewing, and knowledge about oocyte donation, were associated with feelings towards oocyte donation, by using a univariate conditional logistic regression model. This statistical method was also used to assess whether women would be more inclined to consider oocyte donation with the pronuclear transfer technique rather than the whole oocyte donation. All parameters found to be statistically significant in the univariate analysis were subsequently tested in a multivariate model using logistic regression.
    RESULTS: Most women were concerned about the biological genetic contribution of the donated oocyte (94.8%). The most common reason for a women\'s reluctance to donate their oocytes was their unwillingness to pass on their genetic material (33.3%). Nearly 70% of women who were initially hesitant to donate their oocytes indicated that they would reconsider their decision if the oocyte donation was conducted using donated cytoplasm and the pronuclear transfer technique. Concomitantly, >75% of the respondents mentioned that it would be easier to receive a cytoplasm donation. The largest proportion of the population surveyed (94.5%) expressed their support for its legalization.
    CONCLUSIONS: In this study, a substantial portion of the responses came from individuals with medical or paramedical backgrounds, potentially introducing a recruitment bias among potential donors. The rate of missing responses to the question regarding the desire to become an oocyte donor was 13.6%, while the question about becoming an oocyte cytoplasm donor had a missing response rate of 23%. These missing responses may introduce a bias in the interpretation of the data.
    CONCLUSIONS: This study was the first to demonstrate that, for the French population studied, the combination of oocyte cytoplasm donation with pronuclear transfer could offer a promising approach to enhance the acceptance of oocyte donation for both the donor and the recipient.
    BACKGROUND: No external funding was used for this study. The authors have no conflicts of interest.
    BACKGROUND: N/A.
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  • 文章类型: Editorial
    暂无摘要。
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  • 文章类型: Journal Article
    42,374名英国人(1600至2022年)的血统包含与第四表亲相距甚远的亲戚之间的社会结果相关性。这些相关性显示出惊人的模式。首先是跨家谱的社会地位的强烈持久性。每个世代的相关性仅下降0.79倍。即使是第四个表亲,只有五代前的共同祖先,显示出显著的状态相关性。第二个显著特点是,从1600年到2022年,谱系中与遗传距离的相关性下降没有变化。预计1600年至2022年之间英格兰的巨大社会变革将增加社会流动性。然而,2022年的人们与他们的血统亲属在结果上仍然保持着与工业化前英格兰完全相同的关联。第三个令人惊讶的特征是,相关性与加性遗传决定状态的简单模型的相关性相似,婚姻的遗传相关性为0.57。
    A lineage of 422,374 English people (1600 to 2022) contains correlations in social outcomes among relatives as distant as 4th cousins. These correlations show striking patterns. The first is the strong persistence of social status across family trees. Correlations decline by a factor of only 0.79 across each generation. Even fourth cousins, with a common ancestor only five generations earlier, show significant status correlations. The second remarkable feature is that the decline in correlation with genetic distance in the lineage is unchanged from 1600 to 2022. Vast social changes in England between 1600 and 2022 would have been expected to increase social mobility. Yet people in 2022 remain correlated in outcomes with their lineage relatives in exactly the same way as in preindustrial England. The third surprising feature is that the correlations parallel those of a simple model of additive genetic determination of status, with a genetic correlation in marriage of 0.57.
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  • 文章类型: Case Reports
    罗斯综合症是一种罕见的以补品瞳孔为特征的疾病,反射减退,和异常的节段性出汗。该疾病的病理生理学仍不清楚,个别患者报告多汗症或多汗症。我们提出一个男人的案子,57岁,他的右肢出现多汗症,左肢无汗症,和他的瞳孔的变化。该疾病与自身免疫性疾病的标志物无关,这支持了最近关于神经变性作用的研究结果。病人的儿子表现出类似的症状,这意味着遗传遗传在这个过程中。多学科方法对于罗斯综合征患者的诊断和最终治疗至关重要。
    Ross Syndrome is a rare disorder characterized by tonic pupils, hyporeflexia, and abnormal segmental sweating. The pathophysiology of the disease remains unclear, with either hypohidrosis or hyperhidrosis reported in individual patients. We present the case of a man, aged 57 years, who presented with hyperhidrosis in his right extremities, anhidrosis in the left extremities, and changes in his pupils. The disease was not associated with markers of autoimmune disease, which supports recent research findings on the role of neurodegeneration. The patient\'s son was exhibiting similar symptoms, which implicates genetic inheritance in the process. A multidisciplinary approach is crucial for the diagnosis and ultimate management of patients with Ross Syndrome.
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  • 文章类型: Journal Article
    背景:重度抑郁症(MDD)的遗传负荷在生命早期发展为MDD的人群中可能更高。这项研究旨在调查患有MDD的青少年的父母是否更有可能患有MDD,双相情感障碍(BD),精神分裂症(SZ),酒精使用障碍,或物质使用障碍比没有MDD的青少年的父母。我们还检查了对抗抑郁治疗的反应是否预测了父母精神疾病的可能性。
    方法:总之,1,758名12-19岁的青少年患有抗抑郁药抗性抑郁症,包括7,032(1:4)年龄/性别匹配的患有抗抑郁药反应性抑郁症的青少年和7,032(1:4)年龄/性别匹配的对照。对入选个体的父母精神疾病进行评估。
    结果:患有MDD的青少年的父母更有可能被诊断为患有MDD,BD,SZ,酒精使用障碍,或物质使用障碍的父母比对照组。对抗抑郁药耐药的青少年的父母和对治疗耐药或对治疗有反应的青少年的母亲更有可能被诊断出患有精神疾病。
    结论:我们的研究表明,患有MDD的青少年的父母可能更有可能被诊断为MDD,BD,SZ,酒精使用障碍,或物质使用障碍比没有MDD的青少年的父母,提示这些精神疾病的障碍内传播和交叉障碍传播。此外,父母的性别和对抗抑郁治疗的反应可能会影响MDD的疾病内传播。
    BACKGROUND: The genetic load for major depressive disorder (MDD) may be higher in people who develop MDD earlier in life. This study aimed to investigate whether the parents of adolescents with MDD were more likely to have MDD, bipolar disorder (BD), schizophrenic disorder (SZ), alcohol use disorder, or substance use disorder than the parents of adolescents without MDD. We also examined whether the response to antidepressant treatment predicted the likelihood of parental psychiatric disorders.
    METHODS: In all, 1,758 adolescents aged 12-19 years with antidepressant-resistant depression, 7,032 (1:4) age-/sex-matched adolescents with antidepressant-responsive depression and 7,032 (1:4) age-/sex-matched controls were included. Parental psychiatric disorders of individuals enrolled were assessed.
    RESULTS: The parents of the adolescents with MDD were more likely to be diagnosed with MDD, BD, SZ, alcohol use disorder, or substance use disorder than the parents of the control group. The parents of adolescents who were antidepressant resistant and the mothers of adolescents who were either treatment resistant or treatment responsive were more likely to be diagnosed with a psychiatric disorder.
    CONCLUSIONS: Our study demonstrated that parents of adolescents with MDD may be more likely to be diagnosed with MDD, BD, SZ, alcohol use disorder, or substance use disorder than parents of adolescents without MDD, suggesting the within-disorder transmission and cross-disorder transmission of these psychiatric disorders. Furthermore, the parent\'s sex and the response to antidepressant treatment may affect the within-disorder transmission of MDD.
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  • 文章类型: Journal Article
    背景:Chenopodium专辑L.是春季种植的农作物中麻烦的杂草,并且已经记录了这种杂草的不同倍性水平。C.专辑的种群对麦草畏产生了抵抗力。在该种群中研究了麦草畏抗性的倍性和遗传水平。
    结果:通过流式细胞术确认C.alum的抗性和易感个体为四倍体。在十个抗性和易感个体之间进行配对杂交。用400ga.e.ha-1的麦草畏处理后,确认了来自五个杂交的八个F1个体具有抗性。这些人是自交的,在剂量反应实验中评估了其后代对麦草畏的反应,结果证实了抗性性状是显性的。此外,对分离模式的分析表明,当用200、400和800ga.e.ha-1的麦草畏处理时,所有F2后代的分离反应均符合3:1(抗性/易感性)比例,表明一个基因负责麦草畏抗性。
    结论:研究的四倍体C.alum种群中的麦草畏抗性由单个显性基因控制。这种类型的遗传表明对麦草畏抗性的选择可以容易地发生。©2022作者害虫管理科学由JohnWiley&SonsLtd代表化学工业学会出版。
    BACKGROUND: Chenopodium album L. is a troublesome weed in spring-planted crops, and different levels of ploidy have been documented for this weed species. A population of C. album has evolved resistance to dicamba. The level of ploidy and inheritance of dicamba resistance was studied in this population.
    RESULTS: The resistant and susceptible individuals of C. album were confirmed as tetraploid by flow cytometry. Pair-crosses were made between ten resistant and susceptible individuals. Eight F1 individuals from five crosses were confirmed resistant after treating with dicamba at 400 g a.e. ha-1 . These individuals were selfed, and the response of their progenies to dicamba was assessed in dose-response experiments, and the results confirmed the resistance trait was dominant. Furthermore, an analysis of the segregation patterns revealed that the segregation response of all F2 progenies fitted a 3:1 (resistant/susceptible) ratio when treated with dicamba at 200, 400 and 800 g a.e. ha-1 , suggesting a single gene was responsible for dicamba resistance.
    CONCLUSIONS: Dicamba resistance in the studied tetraploid population of C. album is governed by a single dominant gene. This type of inheritance suggests that selection for dicamba resistance can occur readily. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
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  • 文章类型: Case Reports
    该病例报告和文献综述的目的是表明家族性发作性疼痛综合征(FEPS)是一种非炎性遗传遗传性疼痛综合征。一个3岁的男孩出现在我们医院,他的前臂和膝盖以下的下肢疼痛超过3年。验血没有异常,血液涂片,肝肾功能检查,微量元素测试,细胞免疫试验,体液免疫试验,自身抗体测试,C反应蛋白(CRP)检测,红细胞沉降率(ESR)测试,以及肿瘤相关和骨髓细胞学检查。此外,影像学检查结果未见异常。从病人的病史来看,我们发现孩子的母亲有类似疾病的家族史。迄今为止,只有21例FEPS3是由钠电压门控通道α亚基11A(SCN11A)基因突变引起的。虽然发病年龄不同,他们中的大多数是在家庭中继承的。遗传检查结果表明,疼痛主要来自母系的遗传遗传。全外显子基因检测显示,疼痛是由SCN11A基因中c.674G>T和c.671T>C的2个杂合突变引起的。
    The purpose of this case report and literature review is to show that familial episodic pain syndrome (FEPS) is a non-inflammatory genetically inherited pain syndrome. A 3-year-old boy presented at our hospital with pain in both his forearms and lower limbs below the knees for more than 3 years. There were no abnormalities in the blood tests, blood smears, liver and kidney function tests, trace elements tests, cellular immunity test, humoral immunity test, autoantibody tests, C-reactive protein (CRP) test, erythrocyte sedimentation rate (ESR) test, and tumor-related and bone marrow cytology examinations. Additionally, the imaging examination results showed no abnormalities. From the patient\'s medical history, we found that the mother of the child had a family history of a similar disease. To date, only 21 cases of FEPS3 caused by the sodium voltage-gated channel alpha subunit 11A (SCN11A) gene mutation have been reported. Although the age of onset is different, most of them are inherited in families. The results of the genetic examination revealed that the pain mainly came from the genetic inheritance of the maternal family line. The whole exon gene test revealed that the pain was caused by 2 heterozygous mutations of c.674G > T and c.671T > C in the SCN11A gene.
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  • 文章类型: Journal Article
    全球范围内,杂草的除草剂抗性对粮食安全构成威胁。抗性通过一系列生理机制的共同选择而迅速发展,这些生理机制使植物能够在环境胁迫下生存。因此,我们假设胁迫耐受性和除草剂抗性在功能上是相关的。我们解决了两个问题:(i)父母一代的压力是否促进后代抗性的进化?(ii)这种进化是通过非遗传机制介导的吗?我们将草杂草的个体暴露于干旱中,并测试了这是否导致第一代除草剂抗性。就存活率和干重而言,我们发现遭受干旱的父母的后代对除草剂的抵抗力增强。我们的结果表明,杂草暴露于干旱可以在后代中赋予除草剂抗性,赋予除草剂抗性遗传力的机制是非遗传的。
    Globally, herbicide resistance in weeds poses a threat to food security. Resistance evolves rapidly through the co-option of a suite of physiological mechanisms that evolved to allow plants to survive environmental stress. Consequently, we hypothesize that stress tolerance and herbicide resistance are functionally linked. We address two questions: (i) does exposure to stress in a parental generation promote the evolution of resistance in the offspring? (ii) Is such evolution mediated through non-genetic mechanisms? We exposed individuals of a grass weed to drought, and tested whether this resulted in herbicide resistance in the first generation. In terms of both survival and dry mass, we find enhanced resistance to herbicide in the offspring of parents that had been exposed to drought. Our results suggest that exposure of weeds to drought can confer herbicide resistance in subsequent generations, and that the mechanism conferring heritability of herbicide resistance is non-genetic.
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  • 文章类型: Journal Article
    Irritable bowel syndrome (IBS) is a functional bowel disorder that is highly comorbid with mental disorders. However, few studies have examined the risk of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder, major depressive disorder (MDD), and schizophrenia in the offspring of parents with IBS. We used nationally representative cross-sectional survey data to analyze cross-generational transmission patterns of both IBS and major mental disorders. Odds ratio (OR) was calculated by using logistic regression models with adjustment for potential confounding factors. Offspring of parents with IBS were more likely to develop IBS themselves (OR = 2.41, 95% confidence interval (CI), 2.09-2.78), ADHD (OR = 1.33, 95% CI, 1.08-1.62), and MDD (OR = 1.32, 95% CI, 1.04-1.68) than the controls. Data stratification by parental sex revealed that paternal IBS increased risk of ADHD (OR = 1.34, 95% CI, 1.01-1.77) in the offspring, while maternal IBS increased the risk of MDD (OR = 1.51, 95% CI, 1.11-2.06). This is the first study to reveal parental IBS is associated with IBS, ADHD, and MDD among offspring, suggesting the necessity for early implementation of prevention strategies for at-risk children.
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