基于混合泊松分布的新生突变识别算法北大核心CSCD

对个体而言,不经父母遗传而后天获得的突变称为新生突变,绝大多数癌症都起自新生突变。构建快速精确的变异识别算法将有助于对癌症的研究。然而,针对前期新生突变识别算法准确率不高,且耗时多等问题,本文引入了基于变异位点的先验概率分布模型,运用基于混合泊松分布的期望最大化(EM)算法对新生突变识别算法进行改进与优化,研究了有亲缘关系的新生突变的识别,并在识别精度与运算速度方面与已有算法进行对比。结果表明,基于混合泊松分布的期望最大化算法在提高运算速度的同时降低了假阳性比率,具有良好的识别效果。     

泊松分布在生物学中的应用

泊松分布广泛应用于遗传学的遗传图距计算、生物物理学的辐射生物学的定量分析、病毒学中的病毒感染率计算、分子生物学中一个基因文库所需克隆数的估计、PCR扩增片段保真率的估算以及酵母单双杂交中转化率的估计等学科领域,对此进行了简要评述。     

基于地理加权泊松模型的天然次生林进界株数空间分布与预测

基于帽儿山实验林场2004—2016年森林资源二类调查固定样地(共108块)数据,采用全局Poisson模型和4种空间尺度(2.5、5、10、15 km)下的地理加权泊松模型(geographically weighted Poisson regression, GWPR)对天然次生林进界株数的空间分布进行了研究,并对5种模型的拟合效果以及影响林分进界株数的因子进行了分析,利用莫兰指数描述了模型残差在全局和局域两种水平上的空间自相关性.结果表明: 本文所选的林分及地形因子都显著影响天然次生林进界株数的空间分布,林分平均胸径是最主要的影响因子;在小尺度(2.5 km)下GWPR模型拥有很高的拟合精度,产生了最大范围的模型参数估计值,得到了较好的模型参数局域化空间分布效果;在较小尺度(2.5和5 km)下GWPR模型产生了较小范围的模型残差,模型的稳定性得到提升;在小尺度(2.5 km)下GWPR模型残差的全局空间自相关性达到最低,局域空间自相关性显著减小,并形成了不同观测值少量聚类这一理想的空间分布模式;在对进界株数空间分布的模拟效果上,小尺度(2.5 km)下的局域模型明显好于全局模型.     

基于第二代测序数据识别肿瘤基因突变的工具比较

使用第二代测序数据来发现癌细胞中的基因组突变,一直是很重要的科学应用问题。此研究使用一个癌症病人的大量数据,评估了甄别基因组突变的几个现有工具。经过比较各工具的方法和正确率,本文发现各自都有自己的优点和缺点。针对这些优缺点,本文提供一些建议,让工具使用者能更好地选择合适的工具。     

长白松自然同龄种群分布格局的研究

以长白松（Ｐｉｎｕｓｓｙｌｖｅｓｔｒｉｆｏｒｍｉｓ）种群为例,通过种群发展历史、种群大小结构研究,发现种群的胸径服从正态分布Ｎ（１６．８７,６．８０２）,确认该种群为自然同龄种群．种群的空间分布格局呈很高的均匀性,趋于随机分布甚至均匀分布,分布格局动态表现出由均匀分布向随机分布变化的趋势．     

新生隐球菌Cap59缺陷株ura5突变株的筛选方法*

改进筛选新生隐球菌Cap59荚膜缺陷株ura5突变株的方法。采用硫酸二乙酯化学诱导新生隐球菌Cap59荚膜缺陷株 ,利用 5 氟乳清酸 (5 FOA)反筛选法筛选ura5尿嘧啶合成基因突变株。用新方法筛选到 2株Cap59荚膜缺陷株ura5突变株。建立了一种筛选新生隐球菌荚膜缺陷株ura5突变株的简易方法。     

松褐天牛产卵刻痕在黑松树干上分布规律的研究

调查和分析了松褐天牛Monochamus alternatusHope的产卵刻槽在寄主植物黑松上的分布情况,结果表明：产卵刻槽分布与寄主胸径和树高有一定的相关关系,黑松树干胸径在9～15 cm之间,树高在4～7 m之间最适合天牛产卵危害,其中在胸径9～13 cm范围内产卵刻槽数量最多,在此范围的寄主受天牛为害最重。天牛在胸径＞17 cm或树高＞7 m时,没有产卵刻槽分布。产卵刻槽集中分布于树干1～2 m位置,3 m以上很少有刻槽分布,同时,天牛产卵多在光线充足的地方,其中南面产卵刻槽数量最多。     

松突圆蚧黑蚜小蜂的产卵分布

采用m*－m方法分析了黑蚜小蜂的产卵频数分布,在25种密度组合下,产卵平均拥挤度m*的值从0．09（1：80）增加到2．96（9：5）,并建立了m*与蜂蚧比、m*与平均密度m的回归模型。结果表明,松突圆蚧黑蚜小蜂产复寄生卵的程度与寄生蜂密度呈正相关,与寄主密度呈负相关,产卵呈随机分布。     

混合位置尺度分布中分量参数的统计推断

本文讨论混合位置尺度分布当混合比已知时分量参数的假设检验和区间估计．本文所提出的方法基于广义枢轴模型．当只有感兴趣的参数未知时,检验的实际水平等于名义水平,且各置信域的实际覆盖率等于名义覆盖率．在更一般的场合,检验是相合的,并且各置信域的实际覆盖率趋于名义覆盖率．模拟显示我们的方法是令人满意的．     

枇杷园蜘蛛混合种群空间分布型的动态分析

枇杷园蜘蛛混合种群的空间分布型在不同季节存在差异,其空间分布型主要由枇杷园蜘蛛本身的生殖水平、游猎型和定居型数量的多寡,主要目标害虫的数量及分布,气候环境的变化及其越冬生态习性,枇杷园蜘蛛的种群密度及其种间竞争程度决定。     

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia

There are several lines of evidence supporting the role of de novo mutations as a mechanism for common disorders, such as autism and schizophrenia. First, the de novo mutation rate in humans is relatively high, so new mutations are generated at a high frequency in the population. However, de novo mutations have not been reported in most common diseases. Mutations in genes leading to severe diseases where there is a strong negative selection against the phenotype, such as lethality in embryonic stages or reduced reproductive fitness, will not be transmitted to multiple family members, and therefore will not be detected by linkage gene mapping or association studies. The observation of very high concordance in monozygotic twins and very low concordance in dizygotic twins also strongly supports the hypothesis that a significant fraction of cases may result from new mutations. Such is the case for diseases such as autism and schizophrenia. Second, despite reduced reproductive fitness¹ and extremely variable environmental factors, the incidence of some diseases is maintained worldwide at a relatively high and constant rate. This is the case for autism and schizophrenia, with an incidence of approximately 1% worldwide. Mutational load can be thought of as a balance between selection for or against a deleterious mutation and its production by de novo mutation. Lower rates of reproduction constitute a negative selection factor that should reduce the number of mutant alleles in the population, ultimately leading to decreased disease prevalence. These selective pressures tend to be of different intensity in different environments. Nonetheless, these severe mental disorders have been maintained at a constant relatively high prevalence in the worldwide population across a wide range of cultures and countries despite a strong negative selection against them². This is not what one would predict in diseases with reduced reproductive fitness, unless there was a high new mutation rate. Finally, the effects of paternal age: there is a significantly increased risk of the disease with increasing paternal age, which could result from the age related increase in paternal de novo mutations. This is the case for autism and schizophrenia³. The male-to-female ratio of mutation rate is estimated at about 4–6:1, presumably due to a higher number of germ-cell divisions with age in males. Therefore, one would predict that de novo mutations would more frequently come from males, particularly older males⁴. A high rate of new mutations may in part explain why genetic studies have so far failed to identify many genes predisposing to complexes diseases genes, such as autism and schizophrenia, and why diseases have been identified for a mere 3% of genes in the human genome. Identification for de novo mutations as a cause of a disease requires a targeted molecular approach, which includes studying parents and affected subjects. The process for determining if the genetic basis of a disease may result in part from de novo mutations and the molecular approach to establish this link will be illustrated, using autism and schizophrenia as examples.     

The Multiple Poisson Distribution,Its Characteristics and a Variety of Forms

The multiple Poisson distribution, known under different names, such as generalized Poisson, compound Poisson, composed Poisson, stuttering Poisson, Poisson power series, Poisson-stopped sum distribution, etc., plays an important role in discrete distribution theory. Here we want to show its basic characteristics, the variety of its forms and specify the generalizing distributions.     

Identification of de novo germline mutations and causal genes for sporadic diseases using trio‐based whole‐exome/genome sequencing

Whole‐genome or whole‐exome sequencing (WGS/WES) of the affected proband together with normal parents (trio) is commonly adopted to identify de novo germline mutations (DNMs) underlying sporadic cases of various genetic disorders. However, our current knowledge of the occurrence and functional effects of DNMs remains limited and accurately identifying the disease‐causing DNM from a group of irrelevant DNMs is complicated. Herein, we provide a general‐purpose discussion of important issues related to pathogenic gene identification based on trio‐based WGS/WES data. Specifically, the relevance of DNMs to human sporadic diseases, current knowledge of DNM biogenesis mechanisms, and common strategies or software tools used for DNM detection are reviewed, followed by a discussion of pathogenic gene prioritization. In addition, several key factors that may affect DNM identification accuracy and causal gene prioritization are reviewed. Based on recent major advances, this review both sheds light on how trio‐based WGS/WES technologies can play a significant role in the identification of DNMs and causal genes for sporadic diseases, and also discusses existing challenges.     

Some Approximations of the Borel-Tanner or the Generalized Poisson Distribution

This paper considers some approximations for the Borel-Tanner (Generalized Poisson) sums by using (i) Gram-Charlier Poisson expansion, (ii) Mixture of two Poisson distributions, (iii) Variance stabilizing technique, and (iv) negative binomial distribution. It has been found that the approximation obtained by using the negative binomial distribution seems to be more efficient than the other approximation.     

Statistical Significance of Mutation Frequencies,and the Power of Statistical Testing,Using the Poisson Distribution

The Poisson distribution may be employed to test whether mutation frequencies differ from control frequencies. This paper describes how this testing procedure may be used for either one-tailed or two-tailed hypotheses. It is also shown how the power of the statistical test can be calculated, the power being the probability of correctly concluding the null hypothesis to be false.     

Origin and timing of de novo variants implicated in type 2 von Willebrand disease

Very few studies have shown the real origin and timing of de novo variants (DNV) implicated in von Willebrand disease (VWD). We investigated four families with type 2 VWD. First, we conducted linkage analysis using single nucleotide variant genotyping to recognize the possible provenance of DNV. Second, we performed amplification refractory mutation system‐quantitative polymerase chain reaction to confirm the real origin of variant (~0% mutant cells) or presence of a genetic mosaic variant (0%–50% mutant cells) in three embryonic germ layer‐derived tissues and sperm cells. Then, three possible timings of DNV were categorized based on the relative likelihood of occurrence according to the number of cell divisions during embryogenesis. Two each with type 2B VWD (proband 1 p.Arg1308Cys, proband 4 p.Arg1306Trp) and type 2A VWD (proband 2 p.Leu1276Arg, proband 3 p.Ser1506Leu) were identified. Variant origins were identified for families 1, 2 and 3 and confirmed to originate from the mother, father and father, respectively. However, the father of family 4 was confirmed to have isolated germline mosaicism with 2.2% mutant sperm cells. Further investigation confirmed the paternal grandfather to be the origin of variant. Thus, we proposed that DNV originating from the two fathers most likely occurred at the single sperm cell, the one originating from the mother occurred at the zygote during the first few cellular divisions; alternatively, in family 4, the DNV most likely occurred at the early postzygotic development in the father. Our findings are essential for understanding genetic pathogenesis and providing accurate genetic counselling.     

Evolutionary history inferred from the de novo assembly of a nonmodel organism,the blue‐eyed black lemur

Lemurs, the living primates most distantly related to humans, demonstrate incredible diversity in behaviour, life history patterns and adaptive traits. Although many lemur species are endangered within their native Madagascar, there is no high‐quality genome assembly from this taxon, limiting population and conservation genetic studies. One critically endangered lemur is the blue‐eyed black lemur Eulemur flavifrons. This species is fixed for blue irises, a convergent trait that evolved at least four times in primates and was subject to positive selection in humans, where 5′ regulatory variation of OCA2 explains most of the brown/blue eye colour differences. We built a de novo genome assembly for E. flavifrons, providing the most complete lemur genome to date, and a high confidence consensus sequence for close sister species E. macaco, the (brown‐eyed) black lemur. From diversity and divergence patterns across the genomes, we estimated a recent split time of the two species (160 Kya) and temporal fluctuations in effective population sizes that accord with known environmental changes. By looking for regions of unusually low diversity, we identified potential signals of directional selection in E. flavifrons at MITF, a melanocyte development gene that regulates OCA2 and has previously been associated with variation in human iris colour, as well as at several other genes involved in melanin biosynthesis in mammals. Our study thus illustrates how whole‐genome sequencing of a few individuals can illuminate the demographic and selection history of nonmodel species.     

基于EST-SSR标记的平欧杂种榛品种鉴定

为建立准确、高效的平欧杂种榛品种鉴定方法,本研究收集目前国内普遍引种的平欧杂种榛品种(品系)43个,选用课题组已开发的12对EST-SSR引物进行品种鉴定方法研究。结果表明:不同引物在供试样品中的PIC值为0.3800~0.7839,平均为0.5113,各引物组合经毛细管电泳均显示出了良好的扩增效果;平欧杂种榛品种(品系)间的亲缘关系较为复杂,其中薄壳红和平欧62、平欧3和平欧7、平欧30和平欧48的遗传距离最近;引物CAF-2、CAF-3、CAF-12和CAF-13组合使用,可完全区分43个平欧杂种榛品种(品系),其中引物CAF-2与CAF-13组合使用,可鉴定16个主栽品种(品系)。上述研究结果为平欧杂种榛的品种鉴定提供了便捷、有效的方法,也可为其他榛属植物研究提供参考。     

Run or Die in the Evolution of New MicroRNAs—Testing the Red Queen Hypothesis on De Novo New Genes

The Red Queen hypothesis depicts evolution as the continual struggle to adapt. According to this hypothesis, new genes, especially those originating from nongenic sequences (i.e., de novo genes), are eliminated unless they evolve continually in adaptation to a changing environment. Here, we analyze two Drosophila de novo miRNAs that are expressed in a testis-specific manner with very high rates of evolution in their DNA sequence. We knocked out these miRNAs in two sibling species and investigated their contributions to different fitness components. We observed that the fitness contributions of miR-975 in Drosophila simulans seem positive, in contrast to its neutral contributions in D. melanogaster, whereas miR-983 appears to have negative contributions in both species, as the fitness of the knockout mutant increases. As predicted by the Red Queen hypothesis, the fitness difference of these de novo miRNAs indicates their different fates.