BACKGROUND & AIMS: :Transmission from the vertebrate host to the mosquito vector represents a major population bottleneck in the malaria life cycle that can successfully be targeted by intervention strategies. However, to date only about 25 parasite proteins expressed during this critical phase have been functionally analysed by gene disruption. We describe the first systematic, larger scale generation and phenotypic analysis of Plasmodium berghei knockout (KO) lines, characterizing 20 genes encoding putatively secreted proteins expressed by the ookinete, the parasite stage responsible for invasion of the mosquito midgut. Of 12 KO lines that were generated, six showed significant reductions in parasite numbers during development in the mosquito, resulting in a block in transmission of five KOs. While expression data, time point of essential function and mutant phenotype correlate well in three KOs defective in midgut invasion, in three KOs that fail at sporulation, maternal inheritance of the mutant phenotype suggests that essential function occurs during ookinete formation and thus precedes morphological abnormalities by several days.

背景与目标： ：从脊椎动物宿主到蚊媒的传播代表了疟疾生命周期中的主要人口瓶颈，可以通过干预策略成功地将其作为目标。然而，迄今为止，在该关键阶段表达的大约25种寄生虫蛋白已通过基因破坏进行了功能分析。我们描述了伯氏疟原虫基因敲除（KO）线的第一个系统的，大规模的生成和表型分析，表征了由假定的由蚊子表达的寄生虫阶段所表达的假定的分泌蛋白编码的20个基因。在产生的12条KO系中，有6条在蚊子的发育过程中显示出寄生虫数量的显着减少，导致5个KO的传播受阻。虽然表达数据，基本功能的时间点和突变体表型在中肠侵袭缺陷的三个KO中有很好的相关性，但在三个孢子形成失败的KO中，突变体表型的母体遗传表明基本功能发生在卵形细胞形成期间，因此先于形态异常发生。几天。

BACKGROUND & AIMS: :The clinical importance of microbiomes to the chronicity of wounds is widely appreciated, yet little is understood about patient-specific processes shaping wound microbiome composition. Here, a two-cohort microbiome-genome wide association study is presented through which patient genomic loci associated with chronic wound microbiome diversity were identified. Further investigation revealed that alternative TLN2 and ZNF521 genotypes explained significant inter-patient variation in relative abundance of two key pathogens, Pseudomonas aeruginosa and Staphylococcus epidermidis. Wound diversity was lowest in Pseudomonas aeruginosa infected wounds, and decreasing wound diversity had a significant negative linear relationship with healing rate. In addition to microbiome characteristics, age, diabetic status, and genetic ancestry all significantly influenced healing. Using structural equation modeling to identify common variance among SNPs, six loci were sufficient to explain 53% of variation in wound microbiome diversity, which was a 10% increase over traditional multiple regression. Focusing on TLN2, genotype at rs8031916 explained expression differences of alternative transcripts that differ in inclusion of important focal adhesion binding domains. Such differences are hypothesized to relate to wound microbiomes and healing through effects on bacterial exploitation of focal adhesions and/or cellular migration. Related, other associated loci were functionally enriched, often with roles in cytoskeletal dynamics. This study, being the first to identify patient genetic determinants for wound microbiomes and healing, implicates genetic variation determining cellular adhesion phenotypes as important drivers of infection type. The identification of predictive biomarkers for chronic wound microbiomes may serve as risk factors and guide treatment by informing patient-specific tendencies of infection.

背景与目标： ：微生物组对伤口慢性的临床重要性已广为人知，但对塑造伤口微生物组组成的患者特定过程知之甚少。在这里，提出了一项两队列微生物组-基因组广泛关联研究，通过该研究鉴定了与慢性伤口微生物组多样性有关的患者基因组位点。进一步的调查表明，替代的TLN2和ZNF521基因型解释了两种关键病原体（铜绿假单胞菌和表皮葡萄球菌）相对丰度的重大患者间差异。在铜绿假单胞菌感染的伤口中，伤口的多样性最低，伤口多样性的降低与治愈率之间存在显着的负线性关系。除了微生物组的特征外，年龄，糖尿病状态和遗传背景均显着影响愈合。使用结构方程模型识别SNP之间的共同方差，六个位点足以解释伤口微生物组多样性的53％的变化，这比传统的多元回归提高了10％。着眼于TLN2，rs8031916的基因型解释了替代转录本的表达差异，该差异在包含重要的粘着结合域方面也有所不同。假设这种差异与伤口微生物组和通过对粘着斑粘附和/或细胞迁移的细菌利用产生影响有关。相关的其他相关基因座功能丰富，通常在细胞骨架动力学中起作用。这项研究是第一个确定伤口微生物组和愈合的患者遗传决定因素的研究，涉及确定细胞粘附表型为感染类型重要驱动因素的遗传变异。慢性伤口微生物组的预测性生物标志物的鉴定可作为危险因素，并通过告知患者特定的感染趋势来指导治疗。

BACKGROUND & AIMS: :Hereditary diffuse gastric cancer and tylosis are autosomal dominant cancer susceptibility syndromes. Accumulating evidence also suggests a genetic contribution to Barrett's esophagus and adenocarcinoma, traditionally considered acquired disorders. In this article we review the current knowledge on the genetic mechanisms underlying hereditary diffuse gastric cancer, tylosis, and Barrett's esophagus. Hereditary diffuse gastric cancer is a paradigm for hereditary cancer susceptibility syndromes with E-cadherin implicated as the dominant oncogene in up to one-third of cases. Tylosis in contrast remains the paradox as whilst the putative abnormality has been localized to the long arm of chromosome 17, sequencing of this region has failed to reveal a disease causing mutation. In the case of Barrett's esophagus and adenocarcinoma, although a validated specific disease-associated gene is yet to be identified, the increasing body of evidence of a possible genetic link is paving the way for subsequent prognostic studies such as AspECT (Aspirin Esomeprazole Chemoprevention Trial). For the clinician these advances in understanding are already having implications for practice in terms of improved screening and the stratification of management strategies. As the mechanisms continue to be defined, there is the real possibility that these mechanisms could be exploited or subverted in the design of new therapies. In the meantime, however, clinicians should undertake rigorous biopsy programs to ensure early invasive lesions are detected.

背景与目标： ：遗传性弥漫性胃癌和Tylosis是常染色体显性遗传易感性综合征。越来越多的证据还表明，对巴雷特的食道和腺癌（传统上认为是获得性疾病）有遗传贡献。在本文中，我们回顾了有关遗传性弥漫性胃癌，Tylosis和Barrett食道的遗传机制的最新知识。遗传性弥漫性胃癌是遗传性癌症易感性综合征的范例，在多达三分之一的病例中，E-钙粘着蛋白被认为是主要的癌基因。相反，由于假定的异常定位在第17号染色​​体的长臂上，因此Tylosis仍然是一个悖论。对该区域的测序未能揭示引起突变的疾病。就Barrett食道和腺癌而言，尽管尚未确定经过验证的与疾病相关的特定基因，但越来越多的可能的遗传关联证据为诸如AspECT（阿司匹林，埃索美拉唑化学预防试验）等后续预后研究铺平了道路。 。对于临床医生而言，这些理解的进步已经对改善筛查和管理策略分层方面的实践产生了影响。随着机制的不断定义，在新疗法的设计中很可能会利用或颠覆这些机制。但是，与此同时，临床医生应进行严格的活检程序，以确保早期发现侵袭性病变。

BACKGROUND & AIMS: :Gordon syndrome is a rare inherited monogenic form of hypertension, which is associated with hyperkalaemia and metabolic acidosis. Since the recognition of this predominantly autosomal dominant condition in the 1960s, the study of families with Gordon syndrome has revealed four genes WNK1, WNK4, KLHL3, and CUL3 to be implicated in its pathogenesis after a phenotype-genotype correlation was realised. The encoded proteins Kelch-like 3 and Cullin 3 interact to form a ring-like complex to ubiquitinate WNK-kinase 4, which, in normal circumstances, interacts with the sodium chloride co-symporter (NCC), the epithelial sodium channel (ENaC), and the renal outer medullary potassium channel (ROMK) in an inhibitory manner to maintain normokalaemia and normotension. WNK-kinase 1 has an inhibitory action on WNK-kinase 4. Mutations in WNK1, WNK4, KLHL3, and CUL3 all result in the accumulation of WNK-kinase 4 and subsequent hypertension, hyperkalaemia, and metabolic acidosis. This review explains the clinical aspects, disease mechanisms, and molecular genetics of Gordon syndrome.

背景与目标： ：Gordon综合征是一种罕见的遗传性单基因型高血压，与高钾血症和代谢性酸中毒有关。自从1960年代认识到这种主要的常染色体显性遗传状态以来，戈登综合症家族的研究已经揭示了四个基因WNK1，WNK4，KLHL3和CUL3，它们在表型与基因型相关性实现后与其发病机理有关。编码的蛋白Kelch-like 3和Cullin 3相互作用形成环状复合物以泛素化WNK激酶4，在正常情况下，WNK激酶4与氯化钠辅助符号（NCC），上皮钠通道（ENaC）相互作用，以及以抑制方式维持肾脏正常血钾和正常血压的肾外延髓钾通道（ROMK）。 WNK激酶1对WNK激酶4具有抑制作用。WNK1，WNK4，KLHL3和CUL3中的突变均导致WNK激酶4的积累，进而导致高血压，高钾血症和代谢性酸中毒。这篇综述解释了戈登综合症的临床方面，疾病机制和分子遗传学。

BACKGROUND & AIMS: AIM:To assess the progress and impact of genetic studies in the addictions arena and to present this information in a form accessible to the general readership of Addiction. METHODS:Review of the evidence that genes are involved in addiction, approaches to their identification, current findings and the potential implications. RESULTS:Family, twin and adoption studies provide strong evidence that addiction runs in families and that this is determined in part by genetic factors. Two main molecular genetic approaches, namely linkage and association, have been adopted to identify the specific genes involved. Both methods are fraught with problems. Linkage is limited by issues of sensitivity, and association by false positives. Perhaps the strongest finding in psychiatric genetics to date is the impressive effect that a single genetic variant, in the aldehyde dehydrogenase 2 gene, has on drinking behaviour and reducing the risk of developing alcohol dependence. Other findings are currently less robust; however, the implications of elucidating the genetic underpinning of addiction will be profound. CONCLUSIONS:Addiction genetics is a developing science that has yet to prove its worth in the clinical setting.

背景与目标： 目的：评估成瘾领域基因研究的进展和影响，并以成瘾的一般读者可以访问的形式呈现此信息。
方法：回顾基因与成瘾有关的证据，鉴定方法，当前发现和潜在影响。
结果：家庭，双胞胎和收养研究提供了有力的证据，证明成瘾在家庭中蔓延，并且这部分是由遗传因素决定的。已经采用两种主要的分子遗传学方法，即连锁和关联，来鉴定涉及的特定基因。两种方法都充满问题。关联性受到敏感性问题的限制，而关联则受到误报的限制。迄今为止，在精神病学遗传学方面最强的发现可能是醛脱氢酶2基因中的单个遗传变异对饮酒行为和降低发展成酒精依赖风险的令人印象深刻的影响。目前，其他发现还不那么可靠。然而，阐明成瘾的遗传基础的意义将是深远的。
结论：成瘾遗传学是一门发展中的科学，尚未在临床环境中证明其价值。

BACKGROUND & AIMS: :Age-related cognitive decline (ACD) is the gradual process of decreasing of cognitive function over age. Most genetic risk factors for ACD have been identified in European populations and there are no reports in admixed Latin American individuals. We performed admixture mapping, genome-wide association analysis (GWAS), and fine-mapping to examine genetic factors associated with 15-year cognitive trajectory in 1,407 Brazilian older adults, comprising 14,956 Mini-Mental State Examination measures. Participants were enrolled as part of the Bambuí-Epigen Cohort Study of Aging. Our admixture mapping analysis identified a genomic region (3p24.2) in which increased Native American ancestry was significantly associated with faster ACD. Fine-mapping of this region identified a single nucleotide polymorphism (SNP) rs142380904 (β = -0.044, SE = 0.01, p = 7.5 × 10-5) associated with ACD. In addition, our GWAS identified 24 associated SNPs, most in genes previously reported to influence cognitive function. The top six associated SNPs accounted for 18.5% of the ACD variance in our data. Furthermore, our longitudinal study replicated previous GWAS hits for cognitive decline and Alzheimer's disease. Our 15-year longitudinal study identified both ancestry-specific and cosmopolitan genetic variants associated with ACD in Brazilians, highlighting the need for more trans-ancestry genomic studies, especially in underrepresented ethnic groups.

背景与目标： ：年龄相关的认知能力下降（ACD）是随着年龄增长而认知功能逐渐下降的过程。在欧洲人群中已经发现了大多数ACD的遗传风险因素，在混合的拉丁美洲人中没有任何报道。我们进行了混合作图，全基因组关联分析（GWAS）和精细映射，以检查与1,407名巴西老年人的15年认知轨迹有关的遗传因素，包括14,956项迷你精神状态检查措施。参加者参加了Bambuí-Epigen老年研究队列。我们的掺混物作图分析确定了一个基因组区域（3p24.2），其中美洲原住民血统增加与更快的ACD密切相关。对该区域的精细映射鉴定了与ACD相关的单核苷酸多态性（SNP）rs142380904（β＝＝-0.044，SE ＝＝ 0.01，p ＝＝ 7.5 ＝×10-5）。此外，我们的GWAS还鉴定了24个相关的SNP，其中大多数在先前报道过影响认知功能的基因中。在我们的数据中，排名前六位的相关SNP占ACD方差的18.5％。此外，我们的纵向研究复制了先前的GWAS减低认知功能和阿尔茨海默氏病的命中率。我们进行了15年的纵向研究，确定了巴西人与ACD相关的祖先特异性和世界性遗传变异，强调需要进行更多的跨祖先的基因组研究，尤其是在代表性不足的族裔群体中。

BACKGROUND & AIMS: :The role of genetics in heart disease diagnosis and management is expanding daily. Clear genetic components have been found for diseases such as hypertrophic cardiomyopathy, heart failure, and coronary artery disease. Rhythm disturbances with genetic components are atrial fibrillation and long QT syndrome. Gene therapies to treat cardiac diseases include those designed to prevent vein graft stenosis and those that promote coronary angiogenesis.

背景与目标： 遗传学在心脏病诊断和管理中的作用每天都在增加。已发现疾病的明确遗传成分，例如肥厚型心肌病，心力衰竭和冠状动脉疾病。具有遗传成分的节律紊乱是心房颤动和长QT综合征。治疗心脏疾病的基因疗法包括旨在预防静脉移植狭窄的疗法和促进冠状血管生成的疗法。

BACKGROUND & AIMS: :Cyanobacteria are one of the principal sources of volatile organic compounds (VOCs) which cause offensive taste and odor (T&O) in drinking and recreational water, fish, shellfish and other seafood. Although non-toxic to humans, these T&O compounds severely undermine public trust in these commodities, resulting in substantial costs in treatment, and lost revenue to drinking water, aquaculture, food and beverage and tourist/hospitality industries. Mitigation and control have been hindered by the complexity of the communities and processes which produce and modify T&O events, making it difficult to source-track the major producer(s) and the factors governing VOC production and fate. Over the past decade, however, advances in bioinformatics, enzymology, and applied detection technologies have greatly enhanced our understanding of the pathways, the enzymes and the genetic coding for some of the most problematic VOCs produced by cyanobacteria. This has led to the development of tools for rapid and sensitive detection and monitoring for the VOC production at source, and provided the basis for further diagnostics of endogenous and exogenous controls. This review provides an overview of current knowledge of the major cyanobacterial VOCs, the producers, the biochemistry and the genetics and highlight the current applications and further research needs in this area.

背景与目标： ：蓝细菌是挥发性有机化合物（VOC）的主要来源之一，这些挥发性有机化合物在饮用水和娱乐用水，鱼类，贝类和其他海鲜中引起令人反感的味道和气味（T＆O）。尽管这些T＆O化合物对人体无毒，但严重破坏了公众对这些商品的信任，从而导致了可观的治疗费用，并给饮用水，水产养殖，食品和饮料以及旅游/接待业损失了收入。产生和修改T＆O事件的社区和流程的复杂性阻碍了缓解和控制，这使得难以追踪主要生产者以及控制VOC生产和命运的因素。然而，在过去的十年中，生物信息学，酶学和应用检测技术的进步极大地增强了我们对蓝细菌产生的一些最有问题的VOC的途径，酶和遗传编码的理解。这导致开发了用于从源头快速，灵敏地检测和监测VOC生产的工具，并为进一步诊断内源性和外源性控制提供了基础。这篇综述概述了主要蓝藻VOC，生产者，生物化学和遗传学的最新知识，并着重介绍了该领域的当前应用和进一步的研究需求。

BACKGROUND & AIMS: :Apart from classroom presentations to their instructors and peer groups, STEM students have limited opportunities or encouragement to engage in guided communication of scientific concepts to others (family, friends, or the general public). A critical need exists for accurate, comprehensible science to be disseminated to these groups. To develop student proficiency in communication of complex biomolecular concepts impacting diverse audiences, I introduce learning approaches and assessments easily adapted to fit the needs of individual instructors and any molecular biology or biochemistry laboratory or lecture course in a remote/online environment. To help students develop an appreciation of the needs of different audiences and the nuanced drivers of clear communication, I provided them the choice of projects of similar length: Option (1) Create a scientific news release and short podcast or video clip newscast describing a recent advancement in understanding the molecular/biochemical basis of a disease; or Option (2) Create a lesson plan and mini-video designed to teach a simple biochemical or molecular mechanism of disease with learning objectives, a brief activity, and appropriate assessment mechanisms. Students who chose the scientific news release/newscast activity distilled complex biomolecular concepts using the 5 W's of journalism-who, what, where, why, when-and learned to accurately communicate the relevance of advanced scientific discoveries and recent events for a broader audience. Students who chose the lesson plan designed activities centered on biomolecular science concepts that build upon what their audience already knows, revealing possibilities for undergraduates to contribute to educational outreach to secondary school teachers and classes.

背景与目标： ：除了课堂上向其讲师和同龄人的演讲之外，STEM学生在与他人（家人，朋友或公众）进行科学概念的指导性交流方面的机会或鼓励也很有限。迫切需要将准确，易于理解的科学传播给这些群体。为了提高学生对影响不同受众的复杂生物分子概念进行交流的能力，我介绍了适合于个别讲师以及任何分子生物学或生物化学实验室或远程/在线环境中的课程的教学方法和评估方法，可以轻松地适应这些要求。为了帮助学生理解不同受众的需求以及清晰沟通的细微驱动力，我为他们提供了类似时长的项目选择：选项（1）创建科学新闻发布以及简短的播客或视频剪辑新闻播报，描述近期新闻在了解疾病的分子/生化基础方面的进步；或选项（2）创建课程计划和微型视频，以教授简单的疾病生化或分子机制为目标，并提供学习目标，简短活动和适当的评估机制。选择科学新闻发布/新闻播报活动的学生使用新闻的5 W蒸馏了复杂的生物分子概念-他们是谁，什么，在哪里，为什么，何时何地-并学会了向更广泛的受众准确传达先进的科学发现和近期事件的相关性。选择课程计划的学生设计了围绕生物分子科学概念的活动，这些概念建立在听众已经知道的基础上，从而揭示了大学生为中学教师和班级的教育拓展做出贡献的可能性。

BACKGROUND & AIMS: :Salmonella serotype Typhimurium is a facultative intracellular pathogen that causes a systemic infection in naturally, or experimentally, infected mice. After oral contamination, Typhimurium colonizes the ileal mucosa and Peyer's patches and invades draining mesenteric lymph nodes. From these primary sites of infection, bacteria dissiminate to the reticuloendothelial system and proliferate rapidly in spleen and liver. Several virulence factors are encoded by chromosomal genes. The ability of Typhimurium to adhere to and invade epithelial cells has been associated with flagella, pili of type I and mannose-resistant haemagglutinating activity. By comparing the virulence of isogenic strains, it appeared that these traits played a marginal role and were not essential for full virulence expression. It is now clear that other surface structures are important for the invasiness capacity of Typhimurium. To multiply in the reticuloendothelial system, a complete lipopolysaccharide is necessary for the bacteria in resisting serum bactericidal activity and producing tissue damage. Salmonella have evolved a specialized iron-binding ligand, termed enterobactin, to acquire iron necessary for their multiplication. Enterobactin competes with the host iron-binding proteins (transferrin or lactoferrin) to secure the iron required by the bacteria. Though the presence of an enterotoxin in Salmonella is still controversial, there is now substantial evidence to support this concept. Recently, a gene encoding an enterotoxin has been cloned from Typhimurium and expressed in E. coli. Typhimurium strains harbour a 90 kilobases (kb) plasmid which is essential for virulence. This plasmid encodes virulence factors required for replication of Salmonella in liver and spleen. It was postulated that the plasmid allowed Typhimurium to multiply in Kupffer cells and in splenic macrophages. The virulence-associated region of the plasmid restored full virulence to plasmidless strains. Transposon insertion mutagenesis demonstrated the existence of two DNA sequences, designated Vir A and Vir B, which are essential for virulence expression. The Vir A region has been sequenced; it encodes four polypeptides with apparent molecular mass of 27,000, 28,000, 33,000 and 70,000. The Vir B region encodes two polypeptides of 38,000 and 43,000. In an attempt to identify bacterial components contributing to invasion of HeLa cells by Salmonella serovar Typhi, we cloned a 30 kb DNA sequence necessary for entry of bacteria into epithelial cells. However, this sequence is not sufficient for conferring an invasive phenotype to E. coli strains. From this DNA fragment, a short segment of 487 bp was subcloned, sequenced and used as probe to detect Salmonella.(ABSTRACT TRUNCATED AT 400 WORDS)

背景与目标： 沙门氏菌血清型鼠伤寒沙门氏菌是一种兼性的细胞内病原体，可在自然或实验感染的小鼠中引起全身性感染。口腔污染后，鼠伤寒菌定居在回肠粘膜和派伊尔斑片上，并侵入排泄的肠系膜淋巴结。细菌从这些主要的感染部位扩散到网状内皮系统，并在脾脏和肝脏中迅速繁殖。几种毒力因子由染色体基因编码。鼠伤寒杆菌粘附和侵袭上皮细胞的能力与鞭毛，I型菌毛和抗甘露糖的血凝活性有关。通过比较同基因菌株的毒力，看来这些性状只发挥了边际作用，对于完整的毒力表达并不是必不可少的。现在清楚的是，其他表面结构对于鼠伤寒的侵袭能力也很重要。为了在网状内皮系统中繁殖，细菌必须具有完整的脂多糖才能抵抗血清杀菌活性并产生组织损伤。沙门氏菌已经进化出一种专门的铁结合配体，称为肠杆菌素，以获取繁殖所需的铁。肠杆菌素与宿主铁结合蛋白（运铁蛋白或乳铁蛋白）竞争，以确保细菌所需的铁。尽管沙门氏菌中肠毒素的存在仍存在争议，但现在有大量证据支持这一概念。最近，已经从鼠伤寒中克隆了编码肠毒素的基因并在大肠杆菌中表达。鼠伤寒沙门氏菌菌株带有一个90 kb的质粒，该质粒对于毒力至关重要。该质粒编码沙门氏菌在肝和脾中复制所需的毒力因子。推测该质粒允许鼠伤寒杆菌在库普弗细胞和脾巨噬细胞中繁殖。质粒的毒力相关区域恢复了无质粒菌株的全部毒力。转座子插入诱变表明存在两个DNA序列，命名为Vir A和Vir B，这对于毒力表达至关重要。 Vir A区已被测序；它编码四种表观分子量分别为27,000、28,000、33,000和70,000的多肽。 Vir B区编码两个38,000和43,000的多肽。为了鉴定导致鼠伤寒沙门氏菌侵袭HeLa细胞的细菌成分，我们克隆了一个30 k​​b的DNA序列，该序列是细菌进入上皮细胞所必需的。然而，该序列不足以赋予大肠杆菌菌株侵袭性表型。从该DNA片段中克隆了487 bp的短片段，进行了测序并用作检测沙门氏菌的探针。（摘要截短了400字）

BACKGROUND & AIMS: :Although the multiple interacting genes affecting complex traits can readily be dissected, how much genotype-environment interactions contribute to variation in complex traits remains elusive. A recent study that quantified several behavioral phenotypes on the same mouse strains in different laboratories decades apart, shows that some behavioral differences between laboratories remain greatly replicable, whereas others are less robust over time. This report, together with studies from Drosophila, stresses the importance of understanding genotype-environment interactions.

背景与目标： ：尽管可以轻易地分析影响复杂性状的多种相互作用基因，但是基因型-环境相互作用在复杂性状变异中的贡献仍然不清楚。一项最近的研究量化了相隔数十年的不同实验室中相同小鼠品系上的几种行为表型，结果表明，实验室之间的某些行为差异仍然可以很好地复制，而其他的随着时间的推移则不那么稳健。该报告与果蝇研究一起强调了了解基因型与环境相互作用的重要性。

BACKGROUND & AIMS: BACKGROUND:A wide range in antibody titers has been found after immunization with the varicella vaccine, although the basis for these differences has not been described. METHODS:To evaluate the contribution of a genetic component in the immune response to the varicella vaccine, concordance for six-week postimmunization antibody titers was evaluated among 248 biologic siblings who participated in varicella vaccine clinical trials by comparing all pairs of siblings (151 pairs) to all possible unrelated, nonsibling pairs created from within this same cohort (30,477 pairs). RESULTS:Postimmunization antibody titers after 1 varicella vaccine dose were within the range observed historically among healthy vaccinees, with 85.4% of subjects having antibody responses greater than the approximate correlate of protection of 5 gpELISA units. Postimmunization antibody titers within sibling pairs clustered together more than or less than 10 gpELISA units when compared with within nonsibling pairs (P < 0.0001). Postimmunization titers within sibling pairs were also quantitatively closer together than were those within unrelated, nonsibling pairs (P = 0.022). The age-adjusted intraclass correlation coefficient indicated that the heritability of the varicella vaccine immune response is 45% (95% confidence interval of 15-75%). CONCLUSIONS:Similarities in siblings' response to varicella vaccine are supportive of the hypothesis that genetic factors play a role in the antibody response to the varicella vaccine.

背景与目标： 背景：水痘疫苗免疫后发现抗体效价范围很广，尽管尚未描述这些差异的基础。
方法：为了评估遗传成分在水痘疫苗免疫反应中的贡献，通过比较所有成对兄弟姐妹（151对），评估了参加水痘疫苗临床试验的248位生物学兄弟姐妹中六周免疫后抗体滴度的一致性。从同一队列中创建的所有可能的不相关，非同级对（30,477对）。
结果：接种一剂水痘疫苗后的免疫后抗体滴度在健康疫苗史上观察到的范围内，其中85.4％的受试者的抗体应答大于5 gpELISA单位保护的近似相关性。同胞对内的免疫后抗体滴度与非同胞对内的相比大于或小于10 gpELISA单位（P <0.0001）。同胞对中的免疫后效价在数量上也比不相关，非同胞对中的免疫后效价更接近（P = 0.022）。年龄调整后的组内相关系数表明，水痘疫苗免疫反应的遗传度为45％（95％置信区间为15-75％）。
结论：兄弟姐妹对水痘疫苗反应的相似性支持以下假说：遗传因素在对水痘疫苗的抗体反应中起作用。

BACKGROUND & AIMS: :Primary hyperoxaluria type 1 (PH1) is an autosomal recessive inborn error of glyoxylate metabolism caused by a deficiency of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). At the enzymic level, PH1 is usually heterogeneous. Several novel enzymic phenotypes have been identified, including the mistargeting of AGT from the peroxisomes to mitochondria, and the aggregation of AGT in the peroxisomal matrix. Seven PH1-specific point mutations, as well as a number of clinically useful normal polymorphisms, have been found so far in the AGT gene. The molecular elucidation of PH1 has led to changes in almost all aspects of its clinical management, most notably treatment. Liver transplantation as a form of enzyme replacement therapy has been used successfully in the treatment of PH1 over the last 10 years, but the long-term solution lies in gene therapy. Although PH1 is, in many respects, an ideal candidate for gene therapy, the strategies eventually adopted will need to take into account its unique metabolic and enzymic characteristics.

背景与目标： ：原发性高草酸尿症1型（PH1）是由肝脏特有的过氧化物酶体酶丙氨酸：乙醛酸氨基转移酶（AGT）缺乏引起的乙醛酸代谢的常染色体隐性先天性错误。在酶水平上，PH1通常是异质的。已经鉴定出几种新颖的酶表型，包括AGT从过氧化物酶体到线粒体的错误定位，以及AGT在过氧化物酶体基质中的聚集。迄今为止，在AGT基因中发现了七个PH1特异性点突变以及许多临床上有用的正常多态性。 PH1的分子阐明已导致其临床管理几乎所有方面的变化，尤其是治疗。在过去的十年中，肝脏移植作为一种酶替代疗法已成功用于治疗PH1，但长期的解决方案在于基因疗法。尽管在许多方面，PH1是基因治疗的理想候选者，但最终采用的策略仍需考虑其独特的代谢和酶学特征。

BACKGROUND & AIMS: :In the spring semester of 2020, colleges and universities adopted online teaching as the primary modality due to campus closure for social distancing. While lectures could be more readily converted to online classes, biology labs were challenging to handle since students could not physically conduct experiments in lab classrooms. In the present report, various online teaching materials, including educational and research videos, simulation labs, and real research data, were utilized to achieve the learning objectives of the originally in-person lab classes of an upper-level undergraduate genetics course. Furthermore, certain advantages of online teaching, such as detailed and high-quality annotation of lecture slides using the Apple Pencil and iPad, were observed. While online teaching has its unique strengths, it could not provide students with hands-on experience in performing real biology experiments to master technical skills; the latter are essential for students to develop a career in conducting research in an academic or industrial laboratory setting. Hence, a well-designed hybrid modality of using online teaching to complement conventional face-to-face instruction may allow for better teaching in undergraduate biology courses.

背景与目标： ：在2020年春季学期，由于校园因社交疏远而关闭，高校采用在线教学作为主要方式。尽管可以更轻松地将讲座转换为在线课程，但是生物学实验室在处理挑战方面存在挑战，因为学生无法在实验室教室中进行物理实验。在本报告中，利用各种在线教学材料，包括教育和研究视频，模拟实验室和真实的研究数据，以实现高级遗传学本科课程原本面对面的实验室课程的学习目标。此外，还观察到了在线教学的某些优势，例如使用Apple Pencil和iPad进行演讲幻灯片的详细和高质量注释。尽管在线教学具有其独特的优势，但它无法为学生提供进行实际生物学实验以掌握技术技能的动手经验。后者对于学生在学术或工业实验室环境中开展研究事业至关重要。因此，使用在线教学补充常规的面对面教学的精心设计的混合形式可以更好地在本科生物学课程中进行教学。

BACKGROUND & AIMS: :Traits related to energy balance and obesity are exceptionally complex, with varying contributions of genetic susceptibility and interacting environmental factors. The use of mouse models has been a powerful driving force in understanding the genetic architecture of polygenic traits such as obesity. However, the use of mouse models for analysis of complex traits is at an important crossroad. Genome-wide association studies in humans are now leading to direct identification of obesity genes. In this review, we focus on three areas representing the current and future roles of mouse models regarding genetics of complex obesity. First, we summarize increasingly powerful ways to harness the strength of mouse models for discovery of genes affecting polygenic obesity. Second, we examine the status of using a systems biology approach to dissect the genetic architecture of obesity. And third, we explore the effects of recent findings indicating increasing levels of complexity in the nature of variation underlying, and the heritability of, complex traits such as obesity.

背景与目标： ：与能量平衡和肥胖有关的性状异常复杂，遗传易感性和相互作用的环境因素的贡献各不相同。鼠标模型的使用已成为了解肥胖等多基因性状遗传结构的强大动力。但是，使用鼠标模型分析复杂性状正处于重要的十字路口。人类的全基因组关联研究现在正导致肥胖基因的直接鉴定。在这篇综述中，我们集中在三个方面，它们代表了关于复杂肥胖症遗传学的小鼠模型的当前和未来作用。首先，我们总结了越来越强大的方法来利用小鼠模型的力量来发现影响多基因肥胖的基因。其次，我们研究了使用系统生物学方法剖析肥胖症遗传结构的现状。第三，我们探索了最近发现的影响，这些结果表明，潜在的变异性及其复杂性（如肥胖症）的遗传性的复杂性水平不断提高。