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1.
The problem of inferring haplotype phase from a population of genotypes has received a lot of attention recently. This is partly due to the observation that there are many regions on human genomic DNA where genetic recombination is rare (Helmuth, 2001; Daly et al., 2001; Stephens et al., 2001; Friss et al., 2001). A Haplotype Map project has been announced by NIH to identify and characterize populations in terms of these haplotypes. Recently, Gusfield introduced the perfect phylogeny haplotyping problem, as an algorithmic implication of the no-recombination in long blocks observation, together with the standard population-genetic assumption of infinite sites. Gusfield's solution based on matroid theory was followed by direct theta(nm2) solutions that use simpler techniques (Bafna et al., 2003; Eskin et al., 2003), and also bound the number of solutions to the PPH problem. In this short note, we address two questions that were left open. First, can the algorithms of Bafna et al. (2003) and Eskin et al. (2003) be sped-up to O(nm + m2) time, which would imply an O(nm) time-bound for the PPH problem? Second, if there are multiple solutions, can we find one that is most parsimonious in terms of the number of distinct haplotypes. We give reductions that suggests that the answer to both questions is "no." For the first problem, we show that computing the output of the first step (in either method) is equivalent to Boolean matrix multiplication. Therefore, the best bound we can presently achieve is O(nm(omega-1)), where omega < or = 2.52 is the exponent of matrix multiplication. Thus, any linear time solution to the PPH problem likely requires a different approach. For the second problem of computing a PPH solution that minimizes the number of distinct haplotypes, we show that the problem is NP-hard using a reduction from Vertex Cover (Garey and Johnson, 1979).  相似文献   

2.
In Part 1 of this study (Weinbaum et al., 1988) a short time model has been proposed to describe the initial time dependent leakage of macromolecules at short distances (5 microns or less) from the exit of a transient open junction which the authors have hypothesized as a characteristic feature of endothelial cells in the process of turnover (Weinbaum et al., 1985). This open junction pathway has also been proposed (Weinbaum et al., 1988) to be the primary ultrastructural correlate of the 20 nm diameter large pore suggested by Renkin et al. (1977) using the predictions of cylindrical pore theory. The short time model in (Weinbaum et al., 1988), however, has major limitations in that it neglects the interaction between leakage sites, macromolecular entry through other pathways, the finite thickness of the vessel wall and the curvature of the cell perimeter. The longer time model developed herein will attempt to describe each of these features and also present an improved model and analytic solution for the steady state flux and uptake. In the previous steady state model developed by Weinbaum et al. (1985) the effect of the resistance of the transient open junctions and the non-isotropic diffusion in the underlying tissue due to the internal elastic lamina (IEL) were both neglected. New solutions are first presented which describe the effect of these important model refinements on the steady state macromolecular permeability of the major arteries. Time dependent solutions are then presented to predict the transient longer time labeling following the introduction of tracer macromolecules of varying size. These solutions and the corresponding short time solutions in Weinbaum et al. (1988) are the first solutions to our knowledge to describe the difficult time-dependent boundary value problem to determine how the channel exit concentration and flux at a leaky junction vary with time. This is accomplished by casting the boundary value problem in the form of an integral equation for the unknown flux at the cleft exit and then solving this problem using a specially designed numerical technique. The theoretical predictions are used to interpret the behavior of the localized leaks to HRP and albumin that have been reported in Stemerman et al. (1986) and our own recent experiments (Lin et al., 1988).  相似文献   

3.
We develop an approach for microarray differential expression analysis, i.e. identifying genes whose expression levels differ between two or more groups. Current approaches to inference rely either on full parametric assumptions or on permutation-based techniques for sampling under the null distribution. In some situations, however, a full parametric model cannot be justified, or the sample size per group is too small for permutation methods to be valid. We propose a semi-parametric framework based on partial mixture estimation which only requires a parametric assumption for the null (equally expressed) distribution and can handle small sample sizes where permutation methods break down. We develop two novel improvements of Scott's minimum integrated square error criterion for partial mixture estimation [Scott, 2004a,b]. As a side benefit, we obtain interpretable and closed-form estimates for the proportion of EE genes. Pseudo-Bayesian and frequentist procedures for controlling the false discovery rate are given. Results from simulations and real datasets indicate that our approach can provide substantial advantages for small sample sizes over the SAM method of Tusher et al. [2001], the empirical Bayes procedure of Efron and Tibshirani [2002], the mixture of normals of Pan et al. [2003] and a t-test with p-value adjustment [Dudoit et al., 2003] to control the FDR [Benjamini and Hochberg, 1995].  相似文献   

4.
We address the question, related with the origin of the genetic code, of why are there three bases per codon in the translation to protein process. As a follow-up to our previous work (Aldana et al., 1998, Martínez-Mekler et al., 1999a,b), we approach this problem by considering the translocation properties of primitive molecular machines, which capture basic features of ribosomal/messenger RNA interactions, while operating under prebiotic conditions. Our model consists of a short one-dimensional chain of charged particles (rRNA antecedent) interacting with a polymer (mRNA antecedent) via electrostatic forces. The chain is subject to external forcing that causes it to move along the polymer which is fixed in a quasi-one-dimensional geometry. Our numerical and analytic studies of statistical properties of random chain/polymer potentials suggest that, under very general conditions, a dynamics is attained in which the chain moves along the polymer in steps of three monomers. By adjusting the model in order to consider present-day genetic sequences, we show that the above property is enhanced for coding regions. Intergenic sequences display a behavior closer to the random situation. We argue that this dynamical property could be one of the underlying causes for the three-base codon structure of the genetic code  相似文献   

5.
Prostate cancer is one of the most common malignancies.The development and progression of prostate cancer are driven by a series of genetic and epigenetic events including gene amplification that activates oncogenes and chromosomal deletion that inactivates tumor suppressor genes.Whereas gene amplification occurs in human prostate cancer,gene deletion is more common,and a large number of chromosomal regions have been identified to have frequent deletion in prostate cancer,suggesting that tumor suppressor inactivation is more common than oncogene activation in prostatic carcinogenesis (Knuutila et al.,1998,1999;Dong,2001).Among the most frequently deleted chromosomal regions in prostate cancer,target genes such as NKX3-1 from 8p21,PTENfrom 10q23 andATBF1 from 16q22 have been identified by different approaches (He et al.,1997;Li et al.,1997;Sun et al.,2005),and deletion of these genes in mouse prostates has been demonstrated to induce and/or promote prostatic carcinogenesis.For example,knockout of Nkx3-1 in mice induces hyperplasia and dysplasia (Bhatia-Gaur et al.,1999;Abdulkadir et al.,2002) and promotes prostatic tumorigenesis (Abate-Shen et al.,2003),while knockout of Pten alone causes prostatic neoplasia (Wang et al.,2003).Therefore,gene deletion plays a causal role in prostatic carcinogenesis (Dong,2001).  相似文献   

6.
特马豆克阶是奥陶系底部第一个阶,笔石是特马豆克阶高分辨率地层划分与对比的重要化石类群。江南斜坡带是我国早奥陶世特马豆克期漂浮笔石分异度和丰度最高的相区之一,位于该区的湖南益阳南坝剖面,发育有完整的上特马豆克阶笔石地层,特马豆克阶-弗洛阶界线附近地层连续,上特马豆克阶笔石地层研究已取得较大进展,但下特马豆克阶地层缺乏系统研究。近年来,通过对该剖面笔石标本的不间断采集,新识别出下特马豆克阶笔石带Rhabdinopora flabelliformis parabola带。到目前为止,湖南益阳南坝剖面特马豆克阶可以识别出5个笔石带,自下而上依次为:Rhabdinopora flabelliformis parabola带、Adelograptus tenellus带、Aorograptus victoriae带、Araneograptus murrayi带以及Hunnegraptus copiosus带。基于目前已识别出的笔石带,参考国内外同期笔石地层资料,本文详细讨论华南特马豆克期笔石带序列,并与国内外同期地层进行精确对比。  相似文献   

7.
Flow cytometry is extensively used for the isolation of discreet populations of cells from complex pools. The advent of autofluorescent (AFP) reporters such as wild type Green Fluorescent Protein (wtGFP) (Chalfie et al., 1994) and its variants, including enhanced green fluorescent protein (EGFP) and enhanced yellow fluorescent protein (EYFP) (Cormack et al., 1996), as vital reporters opens up the possibility of sorting live reporter-expressing cells. Moreover the use of these reporters in transgenics (Okabe et al., 1997) or mice carrying homologously targeted loci (Godwin et al., 1998) should enable the direct isolation of reporter-expressing cells from any desired lineage. Here we have assessed this approach in transgenic mice. ES cell-mediated transgenesis was used for generating a line of mice that express an autofluorescent EYFP reporter in the heart and part of the neural tube at midgestation. Pools of fluorescent cells harboring and expressing the EYFP reporter were isolated from defined regions of embryos and their origin confirmed by assaying the expression of domain-defined marker genes. Such a tool should prove useful for gaining access to any given lineage that can be fluorescent protein reporter tagged.  相似文献   

8.
The organization and evolution of the subtelomeric and pericentromeric regions of human chromosomes exhibit unique characteristics compared to other regions of the genome. As shown in Fig. 1 the functional elements of the centromere and telomere are comprised of highly repetitive DNA sequences, which are responsible for carrying out the main mechanistic duties of these two regions: chromosome segregation and end replication, respectively. The nature of the repeats in these two regions and their function have been reviewed separately and, therefore, will not be discussed in more detail here (Sullivan et al., 1996, 2001; McEachern et al., 2000; Henikoff et al., 2001). Adjacent to these functional element regions, the centromere and telomere regions share an interesting architecture as depicted in Fig. 1. For both pericentromeric and subtelomeric regions, blocks of recent genomic duplications form a zone of shared sequence homologies between certain subsets of human chromosomes. The dynamic nature and evolutionary history of these regions and the unique DNA sequence adjacent to them will be the focus of this review.  相似文献   

9.
Summary During the last few years much has been learned regarding signals that target proteins into peroxisomes. The emphasis in the near future will undoubtedly shift towards the elucidation of the mechanism of import. The use of mammalian and yeast cells deficient in peroxisome assembly and/or import (Zoeller & Raetz, 1986; Erdmann et al., 1989; Cregg et al., 1990; Morand et al., 1990; Tsukamoto, Yokota & Fujiki, 1990) should provide a handle on the genes (Erdmann et al., 1991; Tsukamoto et al., 1991) involved in these processes. This will have to be coupled with further development of in vitro systems which will permit the dissection of the steps in the translocation of proteins into peroxisomes. Though some progress has been made in the development of such assays (Imanaka et al., 1987; Small et al., 1987, 1988; Miyazawa et al., 1989), the fragility of peroxisomes and the absence of biochemical hallmarks of import (such as protein modifications or proteolytic processing) have hindered progress. Since peroxisomes exist in the form of a reticulum in mammalian cells (Gorgas, 1984), all peroxisome purification schemes (from mammalian cells at least) must undoubtedly rupture the peroxisomes, which then reseal to form vesicular structures. Additionally, the reliance on the latency of catalase alone as a major criterion for the integrity of peroxisomes ignores the fact that many other matrix proteins leak out of peroxisomes at vastly different rates during purification of the organelles (Thompson & Krisans, 1990). In view of these problems, the development of peroxisomal transport assays with semi-intact cells would also constitute an important advance. It is very likely that in the next few years we will witness some major advances in our understanding of the mechanism by which proteins enter this organelle.I would like to thank all the members of my lab and my collaborators, past and present, whose hard work provided the material for this review. This work has been supported by grants from the March of Dimes Foundation (#1081) and the NIH (DK41737).  相似文献   

10.
Idowu et al., in this edition of Plant and Soil describe a welcome new tool that allows farmers to optimize the management of their fields. It is based on a holistic approach that integrates assays of soil physical, chemical and biological parameters into an easily understandable, low-cost and quantitative estimate of soil quality or “health”. It can facilitate tracking and understanding of the short and long term effects of different management approaches on soil (and crop) health. Most of the assays used are based on traditional, labour-intensive techniques. The tool could be improved through employment of assay technologies that are under development. For example, Idowu et al., in this edition investigated the use of near infra-red spectroscopy as a replacement for some of the traditional soil assays. Similarly, future developments in remote spectroscopic assays, using satellite, airborne or land-based platforms may facilitate further improvement.  相似文献   

11.
《The New phytologist》1999,142(3):589-591
In the November 1998 issue of New Phytologist , we published the Tansley review 'Gibberellins: regulating genes and germination' by Sian Ritchie and Simon Gilroy ( New Phytol. (1998) 140 , 363–383). Since its publication, it has come to our attention that text associated with Fig. 4 was omitted during production. The correct figure is reprinted here in full.
We apologise to the author and to our readers for this mistake.
Figure 4. Promoter sequences of various genes expressed in the cereal aleurone and shown to be regulated by GA. The position of each sequence is indicated relative to the start codon. Regions identified as being involved in regulation of the genes are highlighted, as are similar regions in other genes. Sites at which protein has been shown to bind are also indicated. ( a ) Barley Amy 32b (Sutcliff et al ., 1993; Whittier et al ., 1987); wheat Amy 2/54 (Huttley et al ., 1992; Rushton et al ., 1992; Rushton et al ., 1995); barley Amy 46 (Khursheed & Rogers, 1988); barley Amy 2/p155 (Knox et al ., 1987); barley aleurain (Whittier et al ., 1987); barley β-glucanase II (Wolf, 1992); wheat cathepsin B-like (Cejudo et al ., 1992); rice ubiquitin-conjugating enzyme (Chen et al ., 1995). ( b ). Wheat Amy 1/18 (Rushton et al ., 1992); barley Amy pHV 19 (Jacobsen & Close, 1991; Gubler & Jacobsen, 1992)/ Amy 1 / 6-4 (Khursheed & Rogers, 1988; Rogers, Lanahan & Rogers 1994); rice OSamy-a / Amy 3c (Ou-Lee et al ., 1988; Sutcliff et al ., 1991; Yu et al ., 1992; Goldman et al ., 1994); rice Amy 3B (Sutcliffe et al ., 1991); rice OSamy-c (Kim et al ., 1992; Kim & Wu, 1992; Tanida et al ., 1994); rice Amy 1A (Huang et al ., 1990; Itoh et al ., 1995).
Figure 4 ( b ). For legend see facing page.  相似文献   

12.
Plexins and semaphorins are a large family of proteins that are involved in cell movement and response. The importance of plexins and semaphorins has been emphasized by their discovery in many organ systems including the nervous (Nkyimbeng-Takwi and Chapoval, 2011; McCormick and Leipzig, 2012; Yaron and Sprinzak, 2012), epithelial (Miao et al., 1999; Fujii et al., 2002), and immune systems (Takamatsu and Kumanogoh, 2012) as well as diverse cell processes including angiogenesis (Serini et al., 2009; Sakurai et al., 2012), embryogenesis (Perala et al., 2012), and cancer (Potiron et al., 2009; Micucci et al., 2010). Plexins and semaphorins are transmembrane proteins that share a conserved extracellular semaphorin domain (Hota and Buck, 2012). The plexins and semaphorins are divided into four and eight subfamilies respectively based on their structural homology. Semaphorins are relatively small proteins containing the extracellular semaphorin domain and short intracellular tails. Plexins contain the semaphorin domain and long intracellular tails (Hota and Buck, 2012). The majority of plexin and semaphorin research has focused on the nervous system, particularly the developing nervous system, where these proteins are found to mediate many common neuronal cell processes including cell movement, cytoskeletal rearrangement, and signal transduction (Choi et al., 2008; Takamatsu et al., 2010). Their roles in the immune system are the focus of this review.  相似文献   

13.
Six soil samples from natural and cultivated sites of Saudi Arabia were investigated for ciliate diversity, using the non-flooded Petri dish culture method, live observation, and silver impregnation. We identified 135 species, all new for the fauna of Saudi Arabia, of which seven were undescribed: Spathidium alqasabi nov. spec.; Enchelyodon alqasabi nov. spec.; Metauroleptus arabicus nov. gen., nov. spec.; Pseudohemisincirra arabica nov. gen., nov. spec.; Saudithrix terricola? Berger, Al-Rasheid and Foissner, 2006; Oxytricha arabica nov. spec.; and Erimophrya monostyla nov. spec. Based on Spathidium alqasabi, S. seppelti foissneri? Vd'a?ny et al., 2006 and S. seppelti etoschense? Foissner et al., 2002 are raised to species rank; for the latter, a new name is required to avoid homonymy: Spathidium fraterculum nov. nom. The new genus Metauroleptus, which possesses two long and two to three short ventral cirral rows, generates all dorsal kineties intrakinetally and produces caudal cirri exclusively in dorsal kinety 1. Metauroleptus belongs to the hypotrichs, while family classification remains doubtful. The same applies to the new hypotrich genus Pseudohemisincirra, which has frontoventral and transverse cirri, while buccal cirri and caudal cirri are absent. The number of species contained in Saudi Arabian soils, including sand dunes, is in the range reported from other regions of the earth, suggesting that ciliates are well adapted to dry habitats, possibly mainly by their ability to produce very resistant resting cysts, most surviving for a long time due to reduced metazoan predation.  相似文献   

14.
The transmission disequilibrium test (TDT) has been utilized to test the linkage and association between a genetic trait locus and a marker. Spielman et al. (1993) introduced TDT to test linkage between a qualitative trait and a marker in the presence of association. In the presence of linkage, TDT can be applied to test for association for fine mapping (Martin et al., 1997; Spielman and Ewens, 1996). In recent years, extensive research has been carried out on the TDT between a quantitative trait and a marker locus (Allison, 1997; Fan et al., 2002; George et al., 1999; Rabinowitz, 1997; Xiong et al., 1998; Zhu and Elston, 2000, 2001). The original TDT for both qualitative and quantitative traits requires unrelated offspring of heterozygous parents for analysis, and much research has been carried out to extend it to fit for different settings. For nuclear families with multiple offspring, one approach is to treat each child independently for analysis. Obviously, this may not be a valid method since offspring of one family are related to each other. Another approach is to select one offspring randomly from each family for analysis. However, with this method much information may be lost. Martin et al. (1997, 2000) constructed useful statistical tests to analyse the data for qualitative traits. In this paper, we propose to use mixed models to analyse sample data of nuclear families with multiple offspring for quantitative traits according to the models in Amos (1994). The method uses data of all offspring by taking into account their trait mean and variance-covariance structures, which contain all the effects of major gene locus, polygenic loci and environment. A test statistic based on mixed models is shown to be more powerful than the test statistic proposed by George et al. (1999) under moderate disequilibrium for nuclear families. Moreover, it has higher power than the TDT statistic which is constructed by randomly choosing a single offspring from each nuclear family.  相似文献   

15.
The nucleotide (nt) sequences of the genes encoding argininosuccinate synthetase from Escherichia coli K-12 (argG) and Saccharomyces cerevisiae (ARG1) were determined. The deduced amino-acid sequences were compared to each other and to their counterparts in two methanogens and in mammals. Three regions are highly conserved. Two of them appear to contain possible Walker-type nt-binding sites [Walker et al., EMBO J. 1 (1982) 945-951] and are therefore candidates for ATP-binding sites. The third region shows some similarity to a short portion of the N-proximal part of the PurA enzyme which catalyses an analogous reaction.  相似文献   

16.
Summary It is known from the literature that total loss of the short arm causes complete Turner's signs (Hoo, 1975; Therman and Patau, 1974). Partial deletions of the short arm of the X chromosome are in some cases compatible with fertility (Fraccaro et al., 1977; Hoo, 1979), but in other cases they cause a significant ovarial insufficiency with Turner's signs (Giraud et al., 1974) or gonadal dysgenesis (Petrinelli et al., 1978). A common sign for all the patients having the Xp-wwith the break point in the dark band (p113-p21) seems to be a short stature. The presence of other clinical signs is rather irregular. In this work, a 25-year-old female patient having a Xp deficiency in region p21 (46,X,del(X) (qterp21:)) with short stature, primary amenorrhea, sterility, and clear Turner's is described.  相似文献   

17.
本文对采自陕西洛南上湾剖面下寒武统辛集组疑难管状化石Cupitheca进行了研究,系统厘定和描述了两个种,分别为Cupitheca holocyclata和Cupitheca costellata,并对Cupithecidae科进行了重新修订。本文所描述标本的壳体多为次生磷酸盐化保存,壳体表面纹饰保存较好;C.holocyclata管体表面为横向纹饰,C.costellata管体表面为纵向纹饰。C.holocyclata全球广布,如南澳大利亚、南极乔治王岛、格陵兰东北部、加拿大纽芬兰等地皆有报道,产出于下寒武统中上部地层,具有一定的洲际地层对比意义。本文为C.holocyclata在中国首次发现。C.costellata仅发现于华北,即本文所研究的洛南辛集组及其同期地层安徽淮南与霍邱的雨台山组。  相似文献   

18.
广东省南雄盆地白垩系—第三系交界恐龙绝灭问题   总被引:41,自引:6,他引:35  
广东省南雄盆地中的红层可划分为三个群五个组,大致代表了晚白垩世—始新世的沉积.根据绝对年龄、古地磁测定结果和脊椎动物化石组合性质的综合分析,位于地磁极性带 29R 上部的坪岭组和上湖组之间的分界线被确定为 K/T 界线.对晚白垩世恐龙蛋的研究表明,不同"种"的恐龙蛋是在地磁极性带 29R 的中、下部,也就是说在白垩系—第三系交界之前20~30万年期间绝迹的.而且在这一时期内,所有已发现的蛋壳中,绝大多数蛋壳的厚度和显微结构都显示出明显的病理特征,例如根据随机取样统计,Macroolithus yaotunensis 蛋壳异常结构的出现率,最高可达75%.产生病态恐龙蛋壳的生理机制可以根据发生在现生鸟类的相同病理特征来解释.进一步分析恐龙蛋壳的微量元素和稳定同位素组成,结果显示, Pb, Cu, Mn 等9种元素丰度变化在这一时期达到最大峰值, δ~(18)O 也出现正异常.在这一基础上提出,微量元素的污染和气候突然的变化妨碍了正常蛋壳结构的形成,导致了恐龙的绝灭.这一绝灭过程大约经历了20~30万年.  相似文献   

19.
Muscle mitochondrial DNAs from two brothers with mitochondrial myopathy associated with peripheral neuropathy had multiple deletions, most of which started in non-D-loop regions, unlike in an autosomal dominant mitochondrial myopathy (Zeviani, M. et al., Nature 339, 309 (1989)). The non-D-loop regions with deletions were amplified by the polymerase chain reaction and the resulting fragments were subcloned and then sequenced. At least 12 deletions of different lengths in different sites were found. However, all the deletions were flanked by short direct repeats (4-12 base pairs).  相似文献   

20.
The life-long addition of new neurons has been documented in many regions of the vertebrate and invertebrate brain, including the hippocampus of mammals (Altman and Das, 1965; Eriksson et al., 1998; Jacobs et al., 2000), song control nuclei of birds (Alvarez-Buylla et al., 1990), and olfactory pathway of rodents (Lois and Alvarez-Buylla, 1994), insects (Cayre et al., 1996) and crustaceans (Harzsch and Dawirs, 1996; Sandeman et al., 1998; Harzsch et al., 1999; Schmidt, 2001). The possibility of persistent neurogenesis in the neocortex of primates is also being widely discussed (Gould et al., 1999; Kornack and Rakic, 2001). In these systems, an effort is underway to understand the regulatory mechanisms that control the timing and rate of neurogenesis. Hormonal cycles (Rasika et al., 1994; Harrison et al., 2001), serotonin (Gould, 1999; Brezun and Daszuta, 2000; Beltz et al., 2001), physical activity (Van Praag et al., 1999) and living conditions (Kemperman and Gage, 1999; Sandeman and Sandeman, 2000) influence the rate of neuronal proliferation and survival in a variety of organisms, suggesting that mechanisms controlling life-long neurogenesis are conserved across a range of vertebrate and invertebrate species. The present article extends these findings by demonstrating circadian control of neurogenesis. Data show a diurnal rhythm of neurogenesis among the olfactory projection neurons in the crustacean brain, with peak proliferation during the hours surrounding dusk, the most active period for lobsters. These data raise the possibility that light-controlled rhythms are a primary regulator of neuronal proliferation, and that previously-demonstrated hormonal and activity-driven influences over neurogenesis may be secondary events in a complex circadian control pathway.  相似文献   

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