genetic models

遗传模型
  • 文章类型: Journal Article
    临床和临床前研究的证据表明,小脑有助于认知功能,包括社会行为。现在小脑在更广泛的行为中的作用已经得到证实,问题是小脑是否通过调节运动的相同机制对社会行为做出了贡献。这篇评论旨在回答小脑是否通过相同的途径引导运动和社会行为。它专注于小脑细胞的研究,突触,或以细胞类型特定的方式操纵基因,然后测试对社交和运动行为的影响。这些研究表明,在没有异常运动控制的情况下,解剖学限制和小脑皮质范围的操作都可能导致社交障碍,反之亦然。这些研究表明,小脑使用不同的细胞,突触,以及社会和运动行为的分子途径。未来的研究需要关注小脑有助于广泛的神经功能的不同机制。
    Evidence from clinical and preclinical studies has shown that the cerebellum contributes to cognitive functions, including social behaviors. Now that the cerebellum\'s role in a wider range of behaviors has been confirmed, the question arises whether the cerebellum contributes to social behaviors via the same mechanisms with which it modulates movements. This review seeks to answer whether the cerebellum guides motor and social behaviors through identical pathways. It focuses on studies in which cerebellar cells, synapses, or genes are manipulated in a cell-type specific manner followed by testing of the effects on social and motor behaviors. These studies show that both anatomically restricted and cerebellar cortex-wide manipulations can lead to social impairments without abnormal motor control, and vice versa. These studies suggest that the cerebellum employs different cellular, synaptic, and molecular pathways for social and motor behaviors. Future studies warrant a focus on the diverging mechanisms by which the cerebellum contributes to a wide range of neural functions.
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  • 文章类型: Journal Article
    以前的研究已经将遗传学与膝骨关节炎联系起来。血管紧张素转换酶(ACE)基因I/D多态性可能导致OA。然而,证据仍然不一致。这项研究检查了膝关节OA风险和ACE基因I/D多态性。
    我们探索了欧洲PMC,Medline,Scopus,和Cochrane图书馆使用关键字。使用纽卡斯尔-渥太华量表(NOS)评估了三个评估偏倚因素。纳入标准:(1)将研究人群分为膝关节OA患者和健康对照;(2)分析ACE基因I/D多态性;(3)病例对照或横断面调查。非膝关节OA的研究,数据不完整,没有全文被排除在外。使用随机效应模型计算比值比(OR)和95%置信区间(95%CI)。
    总共6项病例对照研究包括1,226名膝关节OA患者和1,145名健康受试者作为对照。我们的汇总分析显示,ACE基因I/D多态性与膝关节OA风险之间的显着关联仅在显性(DDID与II)[OR1.69(95%CI1.14-2.50),p=0.009,I2=72%],和IDvs.II[OR1.37(95%CI1.01-1.86),p=0.04,I2=43%]基因型模型。其他基因型模型,包括隐性(DD与ID+II),等位基因(Dvs.I),DDvs.ID,和DD与II模型未显示与膝关节OA风险显著相关。进一步的回归分析显示,种族和性别可能会影响几种基因型模型中的这些关系。
    显性和ID与ⅡACE基因I/D多态性模子显著增长膝关节OA风险。需要对更大样本和不同种族群体进行更多研究来证实我们的发现。种族亚组分析后,我们研究中的一些遗传模型显示出显著的异质性,大多数研究来自亚洲人口的亚洲国家,几乎没有阿拉伯人的证据。
    UNASSIGNED: Previous studies have linked genetics to knee osteoarthritis. Angiotensin-converting enzyme (ACE) gene I/D polymorphism may cause OA. However, evidence remains inconsistent. This study examines knee OA risk and ACE gene I/D polymorphism.
    UNASSIGNED: We explored Europe PMC, Medline, Scopus, and Cochrane Library using keywords. Three assessment bias factors were assessed using the Newcastle-Ottawa Scale (NOS). Criteria for inclusion: (1) Split the study population into knee OA patients and healthy controls; (2) Analysed the ACE gene I/D polymorphism; (3) Case-control or cross-sectional surveys. Studies with non-knee OA, incomplete data, and no full-text were excluded. The odds ratio (OR) and 95% confidence intervals (95% CI) were calculated using random-effect models.
    UNASSIGNED: A total of 6 case-control studies consist of 1,226 patients with knee OA and 1,145 healthy subjects as controls were included. Our pooled analysis revealed that a significant association between ACE gene I/D polymorphism and risk of knee OA was only seen in the dominant (DD + ID vs. II) [OR 1.69 (95% CI 1.14 - 2.50), p = 0.009, I2 = 72%], and ID vs. II [OR 1.37 (95% CI 1.01- 1.86), p = 0.04, I2 = 43%] genotype models. Other genotype models, including recessive (DD vs. ID + II), alleles (D vs. I), DD vs. ID, and DD vs. II models did not show a significant association with knee OA risk. Further regression analysis revealed that ethnicity and sex may influence those relationships in several genotype models.
    UNASSIGNED: Dominant and ID vs. II ACE gene I/D polymorphism models increased knee OA risk significantly. More research with larger samples and different ethnic groups is needed to confirm our findings. After ethnicity subgroup analysis, some genetic models in our study showed significant heterogeneities, and most studies are from Asian countries with Asian populations, with little evidence on Arabs.
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  • 文章类型: Editorial
    暂无摘要。
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  • 文章类型: Journal Article
    背景:海胆对受精知识有很大的贡献,胚胎发生,和细胞生物学。然而,直到现在,它们不是遗传模式生物,因为它们的世代时间长,缺乏饲养和基因操纵的工具。我们最近建立了海胆Lytechinuspictus,作为一个多代模型,由于其4-6个月的世代时间相对较短,并且易于实验室培养。为了充分利用这种新的多代物种,需要方法来进行生物样本库和共享转基因的皮氏乳杆菌精子。
    结果:这里,我们描述了一种方法,基于精子离子生理学,当储存在0°C时,可保持皮氏L.pictus和Strongylocentrotuspuricatus精子受精至少5-10周。我们还描述了一种冷冻保存这两个物种精子的新方法。两种物种的精子都可以冷冻和解冻至少两次,并且仍然会产生经历变态的幼虫。
    结论:我们描述的简单方法对两个物种都有效,实现>90%的胚胎发育和产生的幼虫经历变态成虫。我们希望这些方法对其他研究海洋无脊椎动物精子的人有用。
    BACKGROUND: Sea urchins have contributed greatly to knowledge of fertilization, embryogenesis, and cell biology. However, until now, they have not been genetic model organisms because of their long generation times and lack of tools for husbandry and gene manipulation. We recently established the sea urchin Lytechinus pictus, as a multigenerational model Echinoderm, because of its relatively short generation time of 4-6 months and ease of laboratory culture. To take full advantage of this new multigenerational species, methods are needed to biobank and share genetically modified L. pictus sperm.
    RESULTS: Here, we describe a method, based on sperm ion physiology that maintains L. pictus and Strongylocentrotus purpuratus sperm fertilizable for at least 5-10 weeks when stored at 0°C. We also describe a new method to cryopreserve sperm of both species. Sperm of both species can be frozen and thawed at least twice and still give rise to larvae that undergo metamorphosis.
    CONCLUSIONS: The simple methods we describe work well for both species, achieving >90% embryo development and producing larvae that undergo metamorphosis to juvenile adults. We hope that these methods will be useful to others working on marine invertebrate sperm.
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  • 文章类型: Journal Article
    毛轮是马的遗传特征,可能与气质和皮毛颜色有关。毛轮被描述为头发图案的变化,可能采取各种形式,如圆形和线性螺纹。我们首先对发轮(圆形和线性)进行了频率分析。接下来,计算了一个广义非线性模型来评估一些潜在影响因素的重要性,并进行了遗传参数估计。使用ENDOG软件v4.8估计所分析的所有动物的近交系数。与线性螺纹相比,发现圆形毛发螺纹的马更常见。获得的遗传力范围为,总的来说,圆形螺纹(0.20至0.90)和线性螺纹(0.44至0.84)均为中高。在左右位置之间发现了高度的正相关,表明在某些位置有对称的趋势。毛轮的偏侧性也得到了证明,最集中在左侧,尤其是灰色的马,在眼睛中心线下方显示圆形螺纹,在之前的一篇论文中,这与更冷静、更温顺的气质有关。
    Hair whorls are a hereditary feature in horses that may be associated with temperament and coat color. Hair whorls are described as changes in the hair pattern and may take various forms, such as circular and linear whorls. We first carried out a frequency analysis of hair whorls (circular and linear). Next, a Generalized Non-Linear Model was computed to assess the significance of some potential influencing factors, and a genetic parameter estimation was performed. ENDOG software v4.8 was used to estimate the inbreeding coefficient of all the animals analyzed. It was more common to find horses with circular hair whorls than with linear whorls. The heritability ranges obtained were, in general, medium-high for both circular whorls (0.20 to 0.90) and linear whorls (0.44 to 0.84). High positive correlations were found on the between left and right positions, indicating a tendency to symmetry in certain locations. The laterality of hair whorls was also evidenced, with the biggest concentration on the left-hand side, particularly in gray horses, showing circular whorls below the central line of eyes, which has been associated in a previous paper with a calmer and more docile temperament.
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  • 文章类型: Journal Article
    癫痫是一种慢性脑部疾病,考虑到全世界所有年龄段受影响的人数,最常见的神经系统疾病之一。自1993年以来,已经发布了超过20种新型抗癫痫药物(ASM),尽管我们对癫痫发生背后的分子机制的理解取得了重大进展,超过三分之一的患者仍然对现有的治疗方法有抵抗力。部分原因是大多数现有药物仅针对癫痫发作抑制而不是基础过程。了解这种神经系统疾病的起源需要进行人类神经系统和遗传研究。然而,样本量的限制,伦理问题,人体临床试验中对适当对照的要求(许多患者已经接受过抗癫痫药物治疗)强调了对补充模型的要求.到目前为止,癫痫的哺乳动物模型有助于揭示这种疾病的根本原因,但是与动物繁殖相关的高成本,低吞吐量,和监管限制他们的研究限制了他们在药物筛选中的有用性。这里,我们概述了癫痫建模的最新技术,描述了最新使用的黄金标准动物模型,并回顾了该研究领域的可能替代方法。我们的重点将主要放在体外,在体外,和体内幼虫斑马鱼模型有助于癫痫建模和药物筛选中的3R。我们提供了目前可用的药理学和遗传学方法的描述,以及基因编辑方法的持续发展所提供的可能性。特别是基于CRISPR/Cas9的,用于高通量疾病建模和抗癫痫药物测试。
    Epilepsy is a chronic brain disease and, considering the amount of people affected of all ages worldwide, one of the most common neurological disorders. Over 20 novel antiseizure medications (ASMs) have been released since 1993, yet despite substantial advancements in our understanding of the molecular mechanisms behind epileptogenesis, over one-third of patients continue to be resistant to available therapies. This is partially explained by the fact that the majority of existing medicines only address seizure suppression rather than underlying processes. Understanding the origin of this neurological illness requires conducting human neurological and genetic studies. However, the limitation of sample sizes, ethical concerns, and the requirement for appropriate controls (many patients have already had anti-epileptic medication exposure) in human clinical trials underscore the requirement for supplemental models. So far, mammalian models of epilepsy have helped to shed light on the underlying causes of the condition, but the high costs related to breeding of the animals, low throughput, and regulatory restrictions on their research limit their usefulness in drug screening. Here, we present an overview of the state of art in epilepsy modeling describing gold standard animal models used up to date and review the possible alternatives for this research field. Our focus will be mainly on ex vivo, in vitro, and in vivo larval zebrafish models contributing to the 3R in epilepsy modeling and drug screening. We provide a description of pharmacological and genetic methods currently available but also on the possibilities offered by the continued development in gene editing methodologies, especially CRISPR/Cas9-based, for high-throughput disease modeling and anti-epileptic drugs testing.
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  • 文章类型: Meta-Analysis
    背景:两种多态性,据报道,位于FSHR胞内结构域的rs6165和rs6166会影响卵泡发生,类固醇生成和卵母细胞成熟。一些研究强调了FSHR多态性在PCOS中的作用,但这些发现是相互矛盾的。进行了荟萃分析,以破译新出现的观点。
    方法:使用PubMed进行了全面的文献检索,PCOSkb,谷歌学者。新渥太华量表已用于评估每篇文章的质量。为了评估rs6165和rs6166多态性在不同遗传模型下的关联强度,计算具有95%置信区间(CI)的比值比.
    结果:本研究共选取20篇。在汇总分析和种族分层后,多态性rs6165仍然与PCOS的发病无关。此外,rs6166在印度人口中表现出明显的保护,添加剂,和等位基因模型(OR=0.7,CI:0.54-0.9,p=0.006,OR=0.65,CI:0.48-0.89,p=0.006,OR=0.82,CI:0.7-0.95,p=0.01)以及等位基因模型下高加索人群的低至中度风险(OR=1.17,CI:1.04-1.32,p=0.01)。
    结论:这项荟萃分析提示rs6166的GG基因型对PCOS具有保护作用,以特定于人群的方式。
    BACKGROUND: Two polymorphisms, rs6165 and rs6166 located in the intracellular domain of FSHR has been reported to affect folliculogenesis, steroidogenesis and oocyte maturation. Several studies have highlighted the role of FSHR polymorphisms in PCOS but the findings are conflicting. A meta-analysis was carried out to decipher the emerging perspectives.
    METHODS: A comprehensive literature search was made using PubMed, PCOSkb, and Google Scholar. New Ottawa Scale has been utilized to evaluate the quality of each article. To evaluate the strength of association under different genetic models of rs6165 and rs6166 polymorphisms, odds ratio with a 95% confidence interval (CI) was calculated.
    RESULTS: A total of 20 articles were selected for the present study. In pooled analysis and after the stratification by ethnicity, polymorphism rs6165 remains unrelated to the onset of PCOS. Besides, rs6166 exhibits significant protection in the Indian population under recessive, additive, and allele models (OR = 0.7, CI: 0.54-0.9, p = 0.006, OR = 0.65, CI: 0.48-0.89, p = 0.006, OR = 0.82, CI: 0.7-0.95, p = 0.01, respectively) and low to moderate risk in the Caucasian population under allele model (OR = 1.17, CI: 1.04-1.32, p = 0.01).
    CONCLUSIONS: This meta-analysis suggests that GG genotype of rs6166 provides protection against PCOS, in a population-specific manner.
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  • 文章类型: Journal Article
    有据可查的是,大多数经济性状具有复杂的遗传结构,该结构受加性和非加性基因作用的控制。因此,了解这种复杂性状的潜在遗传结构可以帮助理解这些性状如何响应育种和交配程序中的选择。使用全基因组信息计算和估计绵羊经济性状的非加性效应可能很重要,因为非加性基因在基因组育种值的预测准确性和对选择的遗传响应中起着重要作用。
    本研究旨在评估非加性效应(优势和上位性)对绵羊体重性状遗传参数估算的影响。
    这项研究使用了属于752只苏格兰黑脸羔羊的表型和基因型。本研究中考虑的三个活重性状包括在16、20和24周的体重中)。三种遗传模型包括加性(AM)、加法+优势(ADM),加性+优势+上位性(ADEM),被使用。
    16周龄(BW16)体重的狭义遗传力为0.39、0.35和0.23,20周龄(BW20)为0.55、0.54和0.42,最后24周龄(BW24)为0.16、0.12和0.02,ADM,和ADEM模型,分别。加性遗传模型显著优于非加性遗传模型(p<0.01)。BW16,BW20和BW24的优势变异占总表型的38%,6%和30%,分别。此外,上位性变异占这些性状总表型变异的39、0.39和47%,分别。此外,我们的结果表明,活重性状最重要的SNP在3号染色体上(三个SNPS,包括s12606.1,OAR3_221188082.1和OAR3_4106875.1),8(OAR8_16468019.1、OAR8_18067475.1和OAR8_18043643.1),和19(OAR19_18010247.1),根据全基因组关联分析,采用加性和非加性遗传模型。
    结果强调,非加性遗传效应在控制苏格兰黑脸羔羊16-24周龄时的体重变化中起着重要作用。
    预期使用高密度SNP面板以及加性效应和非加性效应的联合建模可以导致对遗传参数的更好估计和预测。
    UNASSIGNED: It\'s well-documented that most economic traits have a complex genetic structure that is controlled by additive and non-additive gene actions. Hence, knowledge of the underlying genetic architecture of such complex traits could aid in understanding how these traits respond to the selection in breeding and mating programs. Computing and having estimates of the non-additive effect for economic traits in sheep using genome-wide information can be important because; non-additive genes play an important role in the prediction accuracy of genomic breeding values and the genetic response to the selection.
    UNASSIGNED: This study aimed to assess the impact of non-additive effects (dominance and epistasis) on the estimation of genetic parameters for body weight traits in sheep.
    UNASSIGNED: This study used phenotypic and genotypic belonging to 752 Scottish Blackface lambs. Three live weight traits considered in this study were included in body weight at 16, 20, and 24 weeks). Three genetic models including additive (AM), additive + dominance (ADM), and additive + dominance + epistasis (ADEM), were used.
    UNASSIGNED: The narrow sense heritability for weight at 16 weeks of age (BW16) were 0.39, 0.35, and 0.23, for 20 weeks of age (BW20) were 0.55, 0.54, and 0.42, and finally for 24 weeks of age (BW24) were 0.16, 0.12, and 0.02, using the AM, ADM, and ADEM models, respectively. The additive genetic model significantly outperformed the non-additive genetic model (p < 0.01). The dominance variance of the BW16, BW20, and BW24 accounted for 38, 6, and 30% of the total phenotypic, respectively. Moreover, the epistatic variance accounted for 39, 0.39, and 47% of the total phenotypic variances of these traits, respectively. In addition, our results indicated that the most important SNPs for live weight traits are on chromosomes 3 (three SNPS including s12606.1, OAR3_221188082.1, and OAR3_4106875.1), 8 (OAR8_16468019.1, OAR8_18067475.1, and OAR8_18043643.1), and 19 (OAR19_18010247.1), according to the genome-wide association analysis using additive and non-additive genetic model.
    UNASSIGNED: The results emphasized that the non-additive genetic effects play an important role in controlling body weight variation at the age of 16-24 weeks in Scottish Blackface lambs.
    UNASSIGNED: It is expected that using a high-density SNP panel and the joint modeling of both additive and non-additive effects can lead to better estimation and prediction of genetic parameters.
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  • 文章类型: Journal Article
    Dairy cattle are highly susceptible to heat stress. Heat stress causes a decline in milk yield, reduced dry matter intake, reduced fertility rates, and alteration of physiological traits (e.g., respiration rate, rectal temperature, heart rates, pulse rates, panting score, sweating rates, and drooling score) and other biomarkers (oxidative heat stress biomarkers and stress response genes). Considering the significant effect of global warming on dairy cattle farming, coupled with the aim to reduce income losses of dairy cattle farmers and improve production under hot environment, there is a need to develop heat tolerant dairy cattle that can grow, reproduce and produce milk reasonably under the changing global climate and increasing temperature. The identification of heat tolerant dairy cattle is an alternative strategy for breeding thermotolerant dairy cattle for changing climatic conditions. This review synthesizes information pertaining to quantitative genetic models that have been applied to estimate genetic parameters for heat tolerance and relationship between measures of heat tolerance and production and reproductive performance traits in dairy cattle. Moreover, the review identified the genes that have been shown to influence heat tolerance in dairy cattle and evaluated the possibility of using them in genomic selection programmes. Combining genomics information with environmental, physiological, and production parameters information is a crucial strategy to understand the mechanisms of heat tolerance while breeding heat tolerant dairy cattle adapted to future climatic conditions. Thus, selection for thermotolerant dairy cattle is feasible.
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  • 文章类型: Journal Article
    根癌农杆菌会在其感染的植物组织上引起容易可见的宏观结构的形成,称为冠gall。早在17世纪,生物学家的记录就注意到了这些不寻常的植物生长,并开始研究它们形成的基础。这些研究最终导致了感染因子的分离,A.根癌,几十年的研究揭示了根癌通过稳定的水平遗传转移到植物中引起冠胆的显着机制。这一基本发现在植物的遗传操作中产生了一系列仍在进行中的应用。由于对根癌农杆菌及其在植物病害中的作用的深入研究,这种病原体被开发为研究许多细菌共有的关键过程的模型,包括发病过程中的宿主感知,DNA转移和毒素分泌,细菌细胞间通讯,质粒生物学,最近,不对称细胞生物学和复合基因组协调和进化。因此,根癌的研究对微生物学和植物生物学的不同领域产生了巨大的影响,远远超出了其显着的农业应用。在这次审查中,我们试图强调根癌的丰富多彩的历史作为一个研究系统,以及当前正在积极展示其作为模型微生物的价值和效用的领域。
    Agrobacterium tumefaciens incites the formation of readily visible macroscopic structures known as crown galls on plant tissues that it infects. Records from biologists as early as the 17th century noted these unusual plant growths and began examining the basis for their formation. These studies eventually led to isolation of the infectious agent, A. tumefaciens, and decades of study revealed the remarkable mechanisms by which A. tumefaciens causes crown gall through stable horizontal genetic transfer to plants. This fundamental discovery generated a barrage of applications in the genetic manipulation of plants that is still under way. As a consequence of the intense study of A. tumefaciens and its role in plant disease, this pathogen was developed as a model for the study of critical processes that are shared by many bacteria, including host perception during pathogenesis, DNA transfer and toxin secretion, bacterial cell-cell communication, plasmid biology, and more recently, asymmetric cell biology and composite genome coordination and evolution. As such, studies of A. tumefaciens have had an outsized impact on diverse areas within microbiology and plant biology that extend far beyond its remarkable agricultural applications. In this review, we attempt to highlight the colorful history of A. tumefaciens as a study system, as well as current areas that are actively demonstrating its value and utility as a model microorganism.
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