BACKGROUND & AIMS: The dendritic distribution of mitral/tufted (M/T) cells in the opossum accessory olfactory bulb (AOB) was investigated using intracellular injection of Lucifer yellow and DiI labeling. Lucifer yellow labeling demonstrated that the primary dendrites of M/T cells are restricted to one of the two subregions (anterior or posterior) of the glomerular layer. When DiI was placed in the anterior or posterior subregion of the glomerular layer, virtually all of the labeled cell bodies in the AOB were located in the anterior or posterior part of the M/T cell layer, respectively. These results demonstrate that the anterior and posterior subregions of the AOB glomerular layer are termination sites for dendrites belonging to distinct populations of M/T cells.

背景与目标： 使用细胞内注射路西法黄和DiI标记研究了负鼠辅助嗅球 (AOB) 中二尖瓣/簇状 (M/T) 细胞的树突分布。路西法黄色标记表明，M/T细胞的主要树突仅限于肾小球层的两个子区域 (前或后) 之一。当将DiI放置在肾小球层的前部或后部子区域时，AOB中几乎所有标记的细胞体分别位于M/T细胞层的前部或后部。这些结果表明，AOB肾小球层的前部和后部亚区是属于M/T细胞不同群体的树突的终止部位。

BACKGROUND & AIMS: OBJECTIVE:Statins reduce inflammation and risk of myocardial infarction (MI). Because the myeloid IgA Fc receptor encoded by FCAR mediates inflammation, we hypothesized that the FCAR Asp92Asn polymorphism is associated with risk of MI and that this risk would be modified by pravastatin. METHODS AND RESULTS:In the placebo arm of the Cholesterol and Recurrent Events (CARE) study, male carriers of the 92Asn allele had an adjusted hazard ratio for incident MI of 1.68 (95% CI 1.10 to 2.57); relative risk reduction by pravastatin was 69% in carriers and 12% in noncarriers (P(interaction)=0.007). In the placebo arm of the all-male West of Scotland Coronary Prevention Study (WOSCOPS), carriers had an adjusted odds ratio for incident coronary heart disease (CHD) of 1.46 (90% CI 1.05 to 2.03); for pravastatin compared with placebo treatment, the adjusted odds ratios were 0.55 (95% CI 0.32 to 0.93) in carriers and 0.65 (95% CI 0.51 to 0.83) in noncarriers (P(interaction)=0.55). CONCLUSIONS:Carriers of 92Asn had increased risk of MI in CARE and increased odds of CHD in WOSCOPS. Pravastatin significantly reduced risk in carriers in both CARE and WOSCOPS. A genotype by treatment interaction was observed in CARE but not in WOSCOPS.

背景与目标：

BACKGROUND & AIMS: :Vitamin D deficiency is associated with osteoporosis and is thought to increase the risk of cancer and CVD. Despite these numerous potential health effects, data on vitamin D status at the population level and within key subgroups are limited. The aims of the present study were to examine patterns of 25-hydroxyvitamin D (25(OH)D) levels worldwide and to assess differences by age, sex and region. In a systematic literature review using the Medline and EMBASE databases, we identified 195 studies conducted in forty-four countries involving more than 168 000 participants. Mean population-level 25(OH)D values varied considerably across the studies (range 4·9-136·2 nmol/l), with 37·3 % of the studies reporting mean values below 50 nmol/l. The highest 25(OH)D values were observed in North America. Although age-related differences were observed in the Asia/Pacific and Middle East/Africa regions, they were not observed elsewhere and sex-related differences were not observed in any region. Substantial heterogeneity between the studies precluded drawing conclusions on overall vitamin D status at the population level. Exploratory analyses, however, suggested that newborns and institutionalised elderly from several regions worldwide appeared to be at a generally higher risk of exhibiting lower 25(OH)D values. Substantial details on worldwide patterns of vitamin D status at the population level and within key subgroups are needed to inform public health policy development to reduce risk for potential health consequences of an inadequate vitamin D status.

背景与目标： 维生素d缺乏与骨质疏松症有关，被认为会增加患癌症和CVD的风险。尽管有这些潜在的健康影响，但人口水平和关键亚组中维生素d状况的数据有限。本研究的目的是检查世界范围内25-羟基维生素d (25(OH)D) 水平的模式，并评估年龄，性别和地区的差异。在使用Medline和EMBASE数据库的系统文献综述中，我们确定了在44个国家进行的195项研究，涉及168 000多名参与者。在整个研究中，平均人口水平25(OH) d值差异很大 (范围为4·9-136·2 nmol/l)，37·3% 的研究报告平均值低于50 nmol/l。在北美观察到最高的25(OH) d值。尽管在亚洲/太平洋和中东/非洲地区观察到与年龄相关的差异，在其他地方没有观察到它们，在任何地区也没有观察到性别相关的差异。研究之间的实质性异质性排除了对人口水平总体维生素d状况的结论。然而，探索性分析，建议来自世界各地的几个地区的新生儿和住院老人似乎普遍处于较低的25(OH) d值的较高风险中。需要在人口水平和关键亚组中详细了解全球范围内的维生素d状况，以告知公共卫生政策制定以降低潜在健康后果的风险维生素d水平不足。

BACKGROUND & AIMS: :Middle East and North Africa (MENA) encompass very unique populations, with a rich history and encompasses characteristic ethnic, linguistic and genetic diversity. The genetic diversity of MENA region has been largely unknown. The recent availability of whole-exome and whole-genome sequences from the region has made it possible to collect population-specific allele frequencies. The integration of data sets from this region would provide insights into the landscape of genetic variants in this region. We integrated genetic variants from multiple data sets systematically, available from this region to create a compendium of over 26 million genetic variations. The variants were systematically annotated and their allele frequencies in the data sets were computed and available as a web interface which enables quick query. As a proof of principle for application of the compendium for genetic epidemiology, we analyzed the allele frequencies for variants in transglutaminase 1 (TGM1) gene, associated with autosomal recessive lamellar ichthyosis. Our analysis revealed that the carrier frequency of selected variants differed widely with significant interethnic differences. To the best of our knowledge, al mena is the first and most comprehensive repertoire of genetic variations from the Arab, Middle Eastern and North African region. We hope al mena would accelerate Precision Medicine in the region.

背景与目标： : 中东和北非 (MENA) 涵盖了非常独特的人口，具有丰富的历史，并包含了独特的种族，语言和遗传多样性。MENA地区的遗传多样性在很大程度上是未知的。该地区最近获得的全外显子组和全基因组序列使收集特定人群的等位基因频率成为可能。来自该地区的数据集的整合将提供对该地区遗传变异景观的见解。我们系统地整合了来自该地区的多个数据集的遗传变异，以创建超过2600万个遗传变异的汇编。对变体进行了系统注释，并计算了它们在数据集中的等位基因频率，并可以作为web界面使用，从而可以快速查询。作为遗传流行病学学纲要应用原理的证明，我们分析了转谷氨酰胺酶1 (TGM1) 基因变异的等位基因频率，与常染色体隐性层状鱼鳞病有关。我们的分析表明，所选变体的载波频率差异很大，种族间差异很大。据我们所知，al mena是来自阿拉伯，中东和北非地区的第一个也是最全面的遗传变异库。我们希望al mena能够加快该地区的精准医学。

BACKGROUND & AIMS: OBJECTIVE:To investigate the simultaneous occurrence of more than 1 Clostridium difficile ribotype in patients' stool samples at the time of diagnostic testing. METHODS:Stool samples submitted for diagnostic testing for the presence of toxigenic C. difficile were obtained for 102 unique patients. A total of 95 single colonies of C. difficile per stool sample were isolated on selective media, subcultured alongside negative (uninoculated) controls, and polymerase chain reaction (PCR) ribotyped using capillary gel electrophoresis. RESULTS:Capillary-based PCR ribotyping was successful for 9,335 C. difficile isolates, yielding a median of 93 characterized isolates per stool sample (range, 69-95). More than 1 C. difficile ribotype was present in 16 of 102 (16%) C. difficile infection (CDI) cases; 2 of the 16 mixtures were composed of at least 3 ribotypes, while the remaining 14 were composed of at least 2. CONCLUSIONS:Deep sampling of patient stool samples coupled with capillary-based PCR ribotyping identified a high rate of mixed CDI cases compared with previous estimates. Studies seeking to quantify the clinical significance of particular C. difficile ribotypes should account for mixed cases of disease.

背景与目标：

BACKGROUND & AIMS: :Nonradioactive sequence-specific oligonucleotide (SSO) probes specific for the HLA-DP beta locus have been used in a simple dot-blot assay to DP beta-type samples amplified by the polymerase chain reaction (pcr) from Caucasoid (n = 24) and Japanese (n = 23) patients with multiple sclerosis (ms) as well as ethnically matched controls. In contrast to previous reports, no DP beta allele was found to be increased in either patient population. However, the results do show a dramatic difference in the allele frequencies between the two control populations, further emphasizing the need for ethnically matched controls in studies of HLA and disease.

背景与目标： : 对hla-dp β 基因座特异的非放射性序列特异性寡核苷酸 (SSO) 探针已用于简单的斑点印迹分析，通过聚合酶链反应 (pcr) 从高加索人 (n = 24) 扩增的DP β 型样品) 和日本 (n = 23) 多发性硬化症患者 (ms) 以及种族匹配的对照。与以前的报告相反，在两种患者人群中均未发现DP β 等位基因增加。然而，结果确实显示了两个对照人群之间等位基因频率的显着差异，进一步强调了在HLA和疾病研究中需要种族匹配的对照。

BACKGROUND & AIMS: :We developed bulked segregant analysis as a method for rapidly identifying markers linked to any specific gene or genomic region. Two bulked DNA samples are generated from a segregating population from a single cross. Each pool, or bulk, contains individuals that are identical for a particular trait or genomic region but arbitrary at all unlinked regions. The two bulks are therefore genetically dissimilar in the selected region but seemingly heterozygous at all other regions. The two bulks can be made for any genomic region and from any segregating population. The bulks are screened for differences using restriction fragment length polymorphism probes or random amplified polymorphic DNA primers. We have used bulked segregant analysis to identify three random amplified polymorphic DNA markers in lettuce linked to a gene for resistance to downy mildew. We showed that markers can be reliably identified in a 25-centimorgan window on either side of the targeted locus. Bulked segregant analysis has several advantages over the use of near-isogenic lines to identify markers in specific regions of the genome. Genetic walking will be possible by multiple rounds of bulked segregation analysis; each new pair of bulks will differ at a locus identified in the previous round of analysis. This approach will have widespread application both in those species where selfing is possible and in those that are obligatorily outbreeding.

背景与目标： : 我们开发了大量的分离物分析，作为一种快速识别与任何特定基因或基因组区域相关的标记的方法。从单个杂交的分离种群中产生两个大量的DNA样本。每个池或整体包含对于特定性状或基因组区域相同但在所有未连接区域任意的个体。因此，这两个大块在选定区域在遗传上是不同的，但在所有其他区域似乎是杂合的。这两个大块可以用于任何基因组区域和任何分离的种群。使用限制性片段长度多态性探针或随机扩增的多态性DNA引物筛选大块的差异。我们已经使用大量的分离物分析来鉴定生菜中的三个随机扩增的多态性DNA标记，这些标记与抗霜霉病的基因相关。我们表明，可以在目标基因座两侧的25厘摩根窗口中可靠地识别出标记。与使用近等基因系鉴定基因组特定区域中的标记相比，大量分离物分析具有多个优势。通过多轮膨胀的分离分析，遗传行走是可能的; 每对新的大块在上一轮分析中确定的基因座上会有所不同。这种方法将在可能自交的物种和强制近交的物种中得到广泛应用。

BACKGROUND & AIMS: :A cross-sectional survey was conducted of sexually transmitted diseases (STDs) and risky behaviors among 407 drug abusers in treatment facilities in 1998. Infections with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), herpes simplex virus type 2 (HSV-2), and syphilis were detected by testing serum antibody levels; chlamydia and gonorrhea were detected by testing nucleic acid levels in urine. Logistic regression analysis was performed to measure associations. Prevalences of antibodies were as follows: to HSV-2, 44.4%; to HCV, 35.1%; to HBV, 29.5%; to HIV, 2.7%. The prevalence of syphilis was 3.4%; of chlamydia, 3.7%; and of gonorrhea, 1.7%. Of the 407 subjects, approximately 62% had markers for 1 of the STDs. HIV infection was associated with African American race, use of smokable freebase (crack) cocaine, and STD history. HBV infection was associated with age >30 years, injecting drugs, needle sharing, a history of treatment for drug abuse, and African American race. HCV infection was associated with an age >30 years, injecting drugs, and needle sharing, and HSV-2 infection with an age >30 years, female sex, and African American race. Syphilis was associated with a history of STDs. High prevalences of STDs among drug abusers indicate the need for integration of STD screening and treatment into drug treatment programs.

背景与目标： : 对1998年治疗机构中的407名吸毒者进行了性传播疾病 (std) 和危险行为的横断面调查。检测血清抗体水平，检测人类免疫缺陷病毒 (HIV) 、乙型肝炎病毒 (HBV) 、丙型肝炎病毒 (HCV) 、单纯疱疹病毒2型 (HSV-2) 、梅毒感染; 检测尿液中核酸水平，检测衣原体和淋病。进行Logistic回归分析以测量关联。抗体的患病率如下: HSV-2，44.4%; HCV，35.1%; HBV，29.5%; HIV，2.7%。梅毒的患病率为3.4%; 衣原体，3.7%; 淋病，1.7%。在407名受试者中，大约62% 名具有1个性病的标志物。HIV感染与非裔美国人种族，使用可吸烟的免费可卡因 (快克) 和性病史有关。HBV感染与年龄> 30岁，注射药物，共用针头，药物滥用治疗史和非裔美国人有关。HCV感染与年龄> 30岁，注射毒品和共用针头有关，HSV-2感染与年龄> 30岁，女性和非裔美国人有关。梅毒与性病史有关。吸毒者中性病的患病率很高，这表明需要将性病筛查和治疗纳入药物治疗计划。

BACKGROUND & AIMS: :This investigation examined differences in symptom patterns of two different trauma samples using the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). MMPI-2s of 122 male combat veterans seeking outpatient treatment for combat-related PTSD were compared with those of 64 PTSD-diagnosed adults seeking outpatient treatment for the effects of child sexual abuse (CSA). We examined variables related to degree of health concerns, depression, somatization, anger and hostility, masculine-feminine traits, paranoid ideation, anxiety, difficulties thinking and concentrating, elevated mood, and social introversion, as well as test-taking attitude. MANOVAs revealed between-group differences on several variables. However, when analyses controlled for the effect of age, nearly all differences disappeared; the only remaining difference was in a scale measuring anger. Thus, it appears CSA survivors and combat veterans are much more similar than different in their clinical presentation on the MMPI-2. Conceptual issues in the assessment of PTSD are discussed.

背景与目标： : 这项调查使用明尼苏达州多相人格量表-2 (MMPI-2) 检查了两种不同创伤样本的症状模式差异。将122名寻求与战斗相关的PTSD进行门诊治疗的男性战斗退伍军人的MMPI-2s与64名经PTSD诊断为儿童性虐待 (CSA) 的门诊治疗的成年人进行了比较。我们研究了与健康问题程度，抑郁，躯体化，愤怒和敌意，男性女性特征，偏执观念，焦虑，思考和集中注意力的困难，情绪低落，社交内向以及应试态度有关的变量。MANOVAs揭示了几个变量的组间差异。但是，当分析控制了年龄的影响时，几乎所有差异都消失了。唯一剩下的差异是衡量愤怒的量表。因此，看来CSA幸存者和战斗退伍军人在MMPI-2上的临床表现要相似得多。讨论了PTSD评估中的概念问题。

BACKGROUND & AIMS: :Tungiasis (sand flea disease) is an ectoparasitic skin disease caused by the female sand flea/jigger flea (Tunga penetrans). As poverty is the major driving force of the disease, it can be called as a poverty-associated plague. It is one of the emerging neglected diseases in Latin America, Caribbean, sub-Saharan Africa, and India. The aim of the present scrutiny was to assess the public health impact of tungiasis, associated risk factors, and emerging opportunities to prevent and control tungiasis. Searches of PubMed, Google Scholar, and online search engines (Google, AOL, and Yahoo) using keywords "parasitic skin disease," "tungiasis," "sand flea," " tungiasis-associated risk factors," "tungiasis prevention and control," and their synonyms were used as a source of references. Searches were made without time limitations. Of 167 potential articles identified by these criteria, 51 appropriate were selected for review. Tungiasis is widespread in the resource-constrained settings of low-income economies. In the tropics, it is highly prevalent among the impoverished populations, but the associated risk factors are often poorly identified and remain uncontrolled. Though it is a self-limiting disease with considerable morbidity, the parasite may cause subsequent secondary morbidity through life-threatening complications and infections like cellulitis, tetanus, and death. However, the direct and indirect sociocultural, economic, and health impact of tungiasis is often undervalued and misunderstood. A systematic assessment on disease burden is still dearth and deficient. Over the decades, tungiasis has been largely neglected by the scientific community, policy makers, and healthcare stakeholders. In the endemic regions, even tungiasis is not listed for the disease control priorities in the regional, national, and international agenda. The majority of the epidermal parasitic skin diseases particularly tungiasis needs a sustainable global scientific research and control policy. This urges intensive efforts to develop a road map that delivers a clear vision towards zero new infection by designing low-cost prevention and control strategies. Besides, there is an urgency to develop culturally appropriate communication techniques and workable collaboration on a global scale by bringing all the stakeholders of endemic countries.

背景与目标： : Tungiasis (沙蚤病) 是由雌性沙蚤/跳蚤 (Tunga penetrans) 引起的一种外部寄生虫性皮肤病。由于贫困是该疾病的主要驱动力，因此可以将其称为与贫困相关的瘟疫。它是拉丁美洲，加勒比海地区，撒哈拉以南非洲和印度新兴的被忽视的疾病之一。本次审查的目的是评估外膜病对公共卫生的影响，相关的危险因素以及预防和控制外膜病的新兴机会。搜索PubMed，Google Scholar和在线搜索引擎 (Google，AOL和Yahoo)，使用关键字 “寄生性皮肤病”，“tungiasis”，“沙蚤”，“tungiasis相关危险因素”，“tungiasis预防和控制，” 和它们的同义词被用作参考文献的来源。搜索没有时间限制。在这些标准确定的167篇潜在文章中，选择了51篇合适的文章进行审查。在低收入经济体资源受限的环境中，突尼斯病很普遍。在热带地区，它在贫困人口中非常普遍，但相关的风险因素往往无法识别，并且仍然不受控制。尽管它是一种具有相当高发病率的自限性疾病，但该寄生虫可能会通过威胁生命的并发症和感染 (如蜂窝织炎，破伤风和死亡) 引起继发疾病。但是，tungiasis对社会文化，经济和健康的直接和间接影响常常被低估和误解。对疾病负担的系统评估仍然缺乏和不足。几十年来，tungiasis在很大程度上被科学界，政策制定者和医疗保健利益相关者所忽视。在流行地区，甚至在区域，国家和国际议程中也没有将tungiasis列为疾病控制重点。大多数表皮寄生性皮肤病，尤其是tungiasis，需要可持续的全球科学研究和控制政策。这敦促加紧努力，制定路线图，通过设计低成本的预防和控制策略，实现零新感染的清晰愿景。此外，迫切需要通过吸引流行国家的所有利益攸关方，在全球范围内发展文化上适当的交流技术和可行的合作。

BACKGROUND & AIMS: A genetic analysis realized, on Tunisian coasts, within and between two populations of a Teleostean (Sardina pilchardus) on one hand, and two populations of their parasitic Copepods (Peroderma cylindricum) on the other hand, reveal that(l) the 14 loci analysed are monomorphic in the Teleostean populations; (II) 3 loci among 13 investigated are polymorphic in the Copepod populations. Statistical tests from deviations of Hardy-Weinberg equilibrium and genotypic homogeneity show the existence of strong gene flows within and between Copepod populations. Thus, it seems that the Teleostean (Sardina pilchardus) and the Copepod (Peroderma cylindricum) constitute at least on Tunisian coasts, two homogeneous taxinomic units.

背景与目标： 在突尼斯沿海地区，一方面在两个硬骨种群 (Sardina pilchardus) 和两个寄生co足类种群 (Peroderma cylindricum) 之间和之间进行的遗传分析表明 (l) 所分析的14个基因座在硬骨种群中是单形的; (II) 在被调查的13个基因座中，有3个基因座在co足类种群中具有多态性。从Hardy-Weinberg平衡和基因型同质性的偏差进行的统计测试表明，co足类种群内部和之间存在强烈的基因流。因此，似乎Teleostean (Sardina pilchardus) 和co足类 (Peroderma cylindriicum) 至少在突尼斯海岸上构成了两个同质的taxinomic单位。

BACKGROUND & AIMS: :Informed consent is an essential requirement prior to clinical trial participation, however some 'vulnerable' groups, such as people with cognitive impairments and those in medical emergency situations, may lack decisional capacity to consent. This raises ethical and practical challenges when designing and conducting clinical trials involving these populations, who are frequently excluded as a result. Despite recent advances in improving informed consent processes, there has been far less attention paid to the enrolment of adults lacking capacity. Exclusion criteria are an important determinant of the external validity of clinical trial results. The exclusion of these populations, and consent-based recruitment biases which arise from the challenges of identifying and involving surrogate decision-makers, leads to trials which are not representative of the clinical population. This article discusses the involvement of adults who lack decisional capacity to consent in clinical trials and presents the advances over the previous decade and the remaining ethical challenges for the inclusion of this under-represented population in research.

背景与目标： : 知情同意是参与临床试验之前的基本要求，但是某些 “弱势” 群体，例如认知障碍患者和医疗紧急情况下的患者，可能缺乏决策同意能力。在设计和进行涉及这些人群的临床试验时，这提出了道德和实践方面的挑战，这些人群经常因此而被排除在外。尽管最近在改善知情同意程序方面取得了进展，但对缺乏能力的成年人的入学关注却少得多。排除标准是临床试验结果外部有效性的重要决定因素。这些人群被排除在外，以及由于识别和涉及替代决策者的挑战而产生的基于同意的招募偏见，导致无法代表临床人群的试验。本文讨论了缺乏决策能力的成年人参与临床试验的情况，并介绍了过去十年的进展以及将这一代表性不足的人群纳入研究的剩余伦理挑战。

BACKGROUND & AIMS: :Understanding the population genetic consequences of habitat heterogeneity requires assessing whether patterns of gene flow correspond to landscape configuration. Studies of the genetic structure of populations are still scarce for Neotropical forest birds. We assessed range-wide genetic structure and contemporary gene flow in the thorn-tailed rayadito (Aphrastura spinicauda), a passerine bird inhabiting the temperate forests of South America. We used 12 microsatellite loci to genotype 582 individuals from eight localities across a large latitudinal range (30°S-56°S). Using population structure metrics, multivariate analyses, clustering algorithms, and Bayesian methods, we found evidence for moderately low regional genetic structure and reduced gene flow towards the range margins. Genetic differentiation increased with geographic distance, particularly in the southern part of the species' distribution where forests are continuously distributed. Populations in the north seem to experience limited gene flow likely due to forest discontinuity, and may comprise a demographically independent unit. The southernmost population, on the other hand, is genetically depauperate and different from all other populations. Different analytical approaches support the presence of three to five genetic clusters. We hypothesize that the genetic structure of the species follows a hierarchical clustered pattern.

背景与目标： : 了解栖息地异质性的种群遗传后果需要评估基因流模式是否与景观配置相对应。对于新热带森林鸟类，对种群遗传结构的研究仍然很少。我们评估了栖息在南美温带森林中的雀形目鸟刺尾rayadio (Aphrastura spinicauda) 的范围内的遗传结构和当代基因流。我们使用12个微卫星基因座对大纬度范围 (30 ° S-56 ° S) 的8个地区的582个个体进行基因型。使用种群结构指标，多元分析，聚类算法和贝叶斯方法，我们发现了适度低区域遗传结构和减少向范围边缘的基因流的证据。遗传分化随着地理距离的增加而增加，尤其是在该物种分布的南部，那里的森林不断分布。北部的人口似乎经历了有限的基因流，这可能是由于森林的不连续性，并且可能是人口统计学上独立的单位。另一方面，最南端的人口在遗传上是不安全的，与所有其他人口都不同。不同的分析方法支持三到五个遗传簇的存在。我们假设该物种的遗传结构遵循分层聚类模式。

BACKGROUND & AIMS: BACKGROUND:Copy Number Variations (CNVs) are gain or loss of DNA segments that are known to play a role in shaping a wide range of phenotypes. In this study, we used two dairy cattle populations, Holstein Friesian and Jersey, to discover CNVs using the Illumina BovineHD Genotyping BeadChip aligned to the ARS-UCD1.2 assembly. The discovered CNVs were investigated for their functional impact and their population genetics features. RESULTS:We discovered 14,272 autosomal CNVs, which were aggregated into 1755 CNV regions (CNVR) from 451 animals. These CNVRs together cover 2.8% of the bovine autosomes. The assessment of the functional impact of CNVRs showed that rare CNVRs (MAF < 0.01) are more likely to overlap with genes, than common CNVRs (MAF ≥ 0.05). The Population differentiation index (Fst) based on CNVRs revealed multiple highly diverged CNVRs between the two breeds. Some of these CNVRs overlapped with candidate genes such as MGAM and ADAMTS17 genes, which are related to starch digestion and body size, respectively. Lastly, linkage disequilibrium (LD) between CNVRs and BovineHD BeadChip SNPs was generally low, close to 0, although common deletions (MAF ≥ 0.05) showed slightly higher LD (r2 = ~ 0.1 at 10 kb distance) than the rest. Nevertheless, this LD is still lower than SNP-SNP LD (r2 = ~ 0.5 at 10 kb distance). CONCLUSIONS:Our analyses showed that CNVRs detected using BovineHD BeadChip arrays are likely to be functional. This finding indicates that CNVs can potentially disrupt the function of genes and thus might alter phenotypes. Also, the population differentiation index revealed two candidate genes, MGAM and ADAMTS17, which hint at adaptive evolution between the two populations. Lastly, low CNVR-SNP LD implies that genetic variation from CNVs might not be fully captured in routine animal genetic evaluation, which relies solely on SNP markers.

背景与目标：

BACKGROUND & AIMS: :Risk assessment for nutrients assumes a single population with a normal distribution of indexes of requirements and excess. Toxic levels are by definition intakes above the upper level; for copper, however, because we lack noninvasive, sensitive biomarkers of storage or early damage from excess, excess is based on the infrequent occurrence of clinical disease, such as unexplained liver cirrhosis. We examine the limitations of this approach for copper given the very low prevalence of clinical and subclinical disease and suggest that the population risk for copper excess be based on hepatic copper loading as a potentially quantifiable measurement. The challenge ahead is to develop biomarkers that predict the population risk of elevated hepatic copper stores and thus the possibility of disease in a population.

背景与目标： : 营养素的风险评估假设单个人群的需求和过量指数呈正态分布。根据定义，毒性水平高于较高水平; 然而，对于铜，由于我们缺乏非侵入性、敏感的生物标志物储存或过量的早期损害，过量是基于临床疾病的罕见发生，如不明原因的肝硬化。鉴于临床和亚临床疾病的患病率非常低，我们研究了这种方法对铜的局限性，并建议铜过量的人群风险基于肝铜负荷作为潜在的可量化度量。未来的挑战是开发生物标志物，以预测肝铜存储升高的人群风险，从而预测人群中疾病的可能性。