基于单体型重构的传递不平衡检验

传递不平衡检验是基于家系检测疾病位点与标记位点之间连锁与连锁不平衡的经典分析方法。论文针对紧密连锁位点,提出了单体型的传递不平衡检验方法,并把此方法用于分析IgA肾病的两紧密连锁位点的基因定位数据。首先在估计核心家系的单体型频率的基础上,重构单体型的传递/未传递的交叉分类表格,然后通过检验此表格的对称性与边缘齐性进行传递不平衡检验,同时,自编Excel宏命令VBA程序,用于家系数据单体型频率估计与重构。此方法充分利用所有家系信息,并能处理缺失数据。C2093T-C2081T的单体型多态性与IgA肾病关联。此方法推广了已有单体型传递不平衡检验。     

三参数Weibull分布参数的估计

主要给出了三参数Weibull分布参数极大似然法估计的一种方法.首先用矩阵法确定样本的均值、标准差和偏差系数;再利用现成的数表粗略地进行分布参数的点估计,然后以这些点估计值作为迭代初始点,用牛顿法进行迭代计算求解由三参数Weibull分布确定的似然方程,最终求得分布参数的估计值.实例表明,结果是令人满意的.     

多个正态总体均值与标准差比在简单树序约束下的最大似然估计

考虑k(k>3)个正态总体均值与标准差(均值和标准差均未知)之比在简单树序约束下最大似然估计的求解问题, 应用保序回归理论给出了计算均值和标准差最大似然估计的迭代算法, 并证明了所给迭代算法是收敛的, 给出了k=7时利用迭代算法的模拟结果.     

极大似然估计的几种求法

极大似然估计是参数估计的一种常用方法.本文探讨了极大似然估计的三种求法,并举例说明了这些方法在解决实际问题中的应用.     

纵向数据半参数Possion回归模型

建立了半参数纵向数据的Possion回归模型,并利用极大似然估计对此模型的参数进行了估计,讨论了它的Fisher信息矩阵,给出了似然方程的Newton-Raphson迭代求解过程.     

完全极大似然估计与分步极大似然估计

得到了完全极大似然估计的一个重要性质和线形模型、指数分布、均匀分布的完全极大似然估计和分步极大似然估计，并与矩估计和极大似然估计进行比较，结果表明了完全极大似然估计和分步极大似然估计的优良性。     

关于对数正态分布参数极大似然估计的讨论

利用图解法研究了由EM算法得出的有数据删失情况下对数正态分布参数的极大似然估计,得到了在Matlab中利用迭代算法计算参数估计值的方法.     

多个正态总体均值与标准差比在简单树序约束下的最大似然估计

考虑k(k>3)个正态总体均值与标准差（均值和标准差均未知）之比在简单树序约束下最大似然估计的求解问题, 应用保序回归理论给出了计算均值和标准差最大似然估计的迭代算法, 并证明了所给迭代算法是收敛的, 给出了k=7时利用迭代算法的模拟结果.     

基于似然深度的指数分布的参数估计

针对传统估计方法如极大似然估计对于服从指数分布且有污染的截尾数据的参数估计并不是很理想的问题,提出使用一种新的估计方法对其进行参数估计,即似然深度估计,并通过两组实验进行对比,结果显示利用似然深度估计方法得到的参数偏差和均方差较小,表明似然深度估计是一种估计服从指数分布且有污染的截尾数据参数的有效方法。     

利用F2群体估计远缘杂交中不育基因的位置和效应的最大似然法

提出了利用F2群体估计远缘杂交中不育基因位点的位置和效应的一种统计方法.利用共显性标记位点的异常分离,用最大似然法可以对不育基因与标记位点之间的重组值进行估计,还可以同时估计雌雄配子的存活率.给出了重组值和雌雄配子存活率的最大似然估计方法以及估计值的方差和置信区间.     

A method for haplotype inference in general pedigrees without recombination

The abundance of single nucleotide polymorphisms (SNPs) makes the haplotype-based method instead of single-maker-oriented method the main approach to association studies on QTL mapping. The key problem in haploptype-based method is how to reconstruct haplotypes from genotype data. Directly assaying haplotypes in diploid individuals by experimental methods is too expensive, therefore the in silico haplotyping-determination methods are the major choice at the present. This paper presents a rapid and reliable algorithm for haplotype reconstruction for tightly linked SNPs in general pedigrees. It is based on six rules and consists of three steps. First, the parental origins of alleles in offspring are assigned conditional on genotypes in parent-offspring trios; second, the redundant haplotypes are eliminated based on the six rules; and finally, the most likely haplotype combinations are chosen via maximum likelihood method. Our method was verified and compared with PEDPHASE by simulated data with different pedigree sizes, numbers of loci, and proportions of missing genotypes. The result shows that our algorithm was superior to PEDPHASE in terms of computing time and accuracy of haplotype estimation. The computing time for 100 runs was 10―15 times less and the accuracy was 4%―10% higher than PEDPHASE. The result also indicates that our method was very robust and was hardly affected by pedigree size, number of loci, and proportion of missing genotypes.     

中国西北少数民族东乡族的Y染色体微卫星单倍型分析

运用国际法医学界推荐的"最小单倍型"共7个微卫星位点(DYS19,DYS389Ⅰ,DYS389Ⅱ,DYS390,DYS391,DYS392,DYS393)和1个高多态性微卫星位点DYS385,采用PCR结合银染显色技术,对采自临夏回族自治区东乡县的133个健康男性个体的DNA,进行了Y染色体8个微卫星的等位基因及单倍型分布状况遗传多态性分析.结果显示,东乡族保留着较高的Y-STR遗传多态性,在测出的66个等位基因中共构建了110种单倍型,单倍型多样性为98.9%,表明该系统有较强的个体识别能力.另外,我们的研究可以为东乡族这一穆斯林民族的起源提供有价值的遗传资料.     

Evolutionary relationships of human populations from an analysis of nuclear DNA polymorphisms

The genetic relationships of human populations have been studied by comparing gene frequency data for protein and blood-group loci of different populations. DNA analysis now promises to be more informative since not only do the DNA coding sequences have more variation than their corresponding proteins but, in addition, noncoding DNA sequences display more extensive polymorphism. We have now studied the frequency of a group of closely linked nuclear DNA polymorphisms (haplotypes) in the beta-globin gene cluster of normal (beta A) chromosomes of individuals from eight diverse populations. We have found that all non-African populations share a limited number of common haplotypes whereas Africans have predominantly a different haplotype not found in other populations. Genetic distance analysis based on these nuclear DNA polymorphisms indicates a major division of human populations into an African and a Eurasian group.     

Detecting recent positive selection in the human genome from haplotype structure

The ability to detect recent natural selection in the human population would have profound implications for the study of human history and for medicine. Here, we introduce a framework for detecting the genetic imprint of recent positive selection by analysing long-range haplotypes in human populations. We first identify haplotypes at a locus of interest (core haplotypes). We then assess the age of each core haplotype by the decay of its association to alleles at various distances from the locus, as measured by extended haplotype homozygosity (EHH). Core haplotypes that have unusually high EHH and a high population frequency indicate the presence of a mutation that rose to prominence in the human gene pool faster than expected under neutral evolution. We applied this approach to investigate selection at two genes carrying common variants implicated in resistance to malaria: G6PD and CD40 ligand. At both loci, the core haplotypes carrying the proposed protective mutation stand out and show significant evidence of selection. More generally, the method could be used to scan the entire genome for evidence of recent positive selection.     

基于局部均值分解的高频金融数据波动率估计

为解决高频数据在风险评估中存在的非线性问题,提出了利用局部均值分解方法实现高频数据波动率估计。首先,采用高频模拟数据验证估计方法的可行性; 其次,将沪深300 指数不同频率收盘价作为研究对象,利用局部均值分解方法估计波动率,计算相对误差统计量。实验结果表明,利用局部均值分解方法可以有效实现高频数据波动率估计和解决高频数据中的非线性问题,随着抽样频率的增加,估计精度逐渐提高。该方法为高频数据波动率非参数估计提供了新的研究思路。     

Polymorphism of human Ia antigens: gene conversion between two DR beta loci results in a new HLA-D/DR specificity

The polymorphic HLA-DR beta-chains are encoded within the human major histocompatibility complex (MHC) by multiple loci resulting from gene duplications. Certain DR haplotypes can be grouped into families based on shared structural factors. We have studied the molecular basis of HLA-DR polymorphism within such a group which includes the haplotypes DR3, DR5 and DRw6. Molecular mapping of the DR beta-chain region allows true allelic comparisons of the two expressed DR beta-chain loci, DR beta I and DR beta III. At the more polymorphic locus, DR beta I, the allelic differences are clustered and may result from gene conversion events over very short distances. The gene encoding the HLA-DR3/Dw3 specificity has been generated by a gene conversion involving the DR beta I and the DR beta III loci of the HLA-DRw6/Dw18 haplotype, as recipient and donor gene, respectively. Based on which allele is found at DR beta III, the less polymorphic locus, two groups of haplotypes can be defined: DRw52a and DRw52b. The generation of HLA-DR polymorphism within the DRw52 supertypic group can thus be accounted for by a succession of gene duplication, divergence and gene conversion.     

机器结构声发射的表征:自由速度和导纳的测量

本文对机器结构声发射的表征作了实验研究.所推荐的源描述符要求对机器与支撑结构的接触点的自由速度作测量,同时对机器的源导纳作测量或估算.本文对平动和转动的速度测量作了讨论,对力和力矩导纳的测量也作了描述.对一个机器家族——为建筑物服务的离心风扇,在三个自由度、多支撑点上的源描述符进行了评价.数据的表示作了简化.从而使得同类型的机器和一个机器中不同振动分量间可以作比较.在所研究的机器中,似乎在低频区垂直力分量引起的发射占主要.然而力矩的贡献却随着频率的增加,其相对重要性也增加,可能在高频区会占据主要地位.     

中国人十四个群体中Gm和Km因子的分布

本文研究了中国昆明汉族、贵州汉族、广西侗族、大连汉族、山东汉族、沈阳朝鲜族、宁夏回族的Gm和Km因子的表型频率及四川、广西、武汉、上海、长春汉族和广西壮族、新疆维吾尔族共十四个群体的Gm单倍型频率、Km基因频率,并用Gm单倍型频率计算了中国14个群体与其他人种国家的3个群体间的遗传距离和这些群体的系统树。结果表明Gm分布不均一,提示早先大陆上存在的两个群体曾发生过迁移和混杂,在新疆维吾尔族和宁夏回族中均发现白种人和黄种人血缘融合的现象。群体中Km频率呈随机分布。     

Functional epistasis on a common MHC haplotype associated with multiple sclerosis

Genes in the major histocompatibility complex (MHC) encode proteins important in activating antigen-specific immune responses. Alleles at adjacent MHC loci are often in strong linkage disequilibrium; however, little is known about the mechanisms responsible for this linkage disequilibrium. Here we report that the human MHC HLA-DR2 haplotype, which predisposes to multiple sclerosis, shows more extensive linkage disequilibrium than other common caucasian HLA haplotypes in the DR region and thus seems likely to have been maintained through positive selection. Characterization of two multiple-sclerosis-associated HLA-DR alleles at separate loci by a functional assay in humanized mice indicates that the linkage disequilibrium between the two alleles may be due to a functional epistatic interaction, whereby one allele modifies the T-cell response activated by the second allele through activation-induced cell death. This functional epistasis is associated with a milder form of multiple-sclerosis-like disease. Such epistatic interaction might prove to be an important general mechanism for modifying exuberant immune responses that are deleterious to the host and could also help to explain the strong linkage disequilibrium in this and perhaps other HLA haplotypes.