The rise and fall of breakpoint reuse depending on genome resolution

<p>Abstract</p> <p>Background</p> <p>During evolution, large-scale genome rearrangements of chromosomes shuffle the order of homologous genome sequences ("synteny blocks") across species. Some years ago, a controversy erupted in genome rearrangement studies over whether rearrangements recur, causing breakpoints to be reused.</p> <p>Methods</p> <p>We investigate this controversial issue using the synteny block's for human-mouse-rat reported by Bourque <it>et al</it>. and a series of synteny blocks we generated using Mauve at resolutions ranging from coarse to very fine-scale. We conducted analyses to test how resolution affects the traditional measure of the breakpoint reuse rate<it>.</it></p> <p>Results</p> <p>We found that the inversion-based breakpoint reuse rate is low at fine-scale synteny block resolution and that it rises and eventually falls as synteny block resolution decreases. By analyzing the cycle structure of the breakpoint graph of human-mouse-rat synteny blocks for human-mouse and comparing with theoretically derived distributions for random genome rearrangements, we showed that the implied genome rearrangements at each level of resolution become more “random” as synteny block resolution diminishes. At highest synteny block resolutions the Hannenhalli-Pevzner inversion distance deviates from the Double Cut and Join distance, possibly due to small-scale transpositions or simply due to inclusion of erroneous synteny blocks. At synteny block resolutions as coarse as the Bourque <it>et al</it>. blocks, we show the breakpoint graph cycle structure has already converged to the pattern expected for a random distribution of synteny blocks.</p> <p>Conclusions</p> <p>The inferred breakpoint reuse rate depends on synteny block resolution in human-mouse genome comparisons. At fine-scale resolution, the cycle structure for the transformation appears less random compared to that for coarse resolution. Small synteny blocks may contain critical information for accurate reconstruction of genome rearrangement history and parameters.</p

Transcatheter Closure of Atrial Septal Defect: Does Age Matter?

Atrial septal defect (ASD) is the most common type of common congenital heart disease (CHD) in adults. During the last decade, there has been a remarkable change in the treatment strategy of ASD, shifting the therapeutic gold standard from surgery to transcatheter closure, along with refinements and the evolution of device technology. Reports on the outcome of transcatheter ASD closure have shown an excellent efficacy as well as a low complication rate. However, the procedural details and/or outcomes of this procedure may be influenced by several factors including morphologic characteristics of the defect, co-morbid diseases, as well as individual factors including age and weight of the patient. Because the risk-benefit relationship in both the very young and the elderly subsets of the patients has not been clearly defined yet, closure of an ASD with device may be potentially subtracted from the treatment option in these patient groups. In this article, we will review the basis for device closure in small children and elderly patients with ASD and provide an overview of the frequently encountered problems

Whole-genome sequencing identifies emergence of a quinolone resistance mutation in a case of Stenotrophomonas maltophilia bacteremia

Whole-genome sequences for Stenotrophomonas maltophilia serial isolates from a bacteremic patient before and after development of levofloxacin resistance were assembled de novo and differed by one single-nucleotide variant in smeT, a repressor for multidrug efflux operon smeDEF. Along with sequenced isolates from five contemporaneous cases, they displayed considerable diversity compared against all published complete genomes. Whole-genome sequencing and complete assembly can conclusively identify resistance mechanisms emerging in S. maltophilia strains during clinical therapy

Fifteen years of research on oral–facial–digital syndromes: from 1 to 16 causal genes

Oral–facial–digital syndromes (OFDS) gather rare genetic disorders characterised by facial, oral and digital abnormalities associated with a wide range of additional features (polycystic kidney disease, cerebral malformations and several others) to delineate a growing list of OFDS subtypes. The most frequent, OFD type I, is caused by a heterozygous mutation in the OFD1 gene encoding a centrosomal protein. The wide clinical heterogeneity of OFDS suggests the involvement of other ciliary genes. For 15 years, we have aimed to identify the molecular bases of OFDS. This effort has been greatly helped by the recent development of whole-exome sequencing (WES). Here, we present all our published and unpublished results for WES in 24 cases with OFDS. We identified causal variants in five new genes (C2CD3, TMEM107, INTU, KIAA0753 and IFT57) and related the clinical spectrum of four genes in other ciliopathies (C5orf42, TMEM138, TMEM231 and WDPCP) to OFDS. Mutations were also detected in two genes previously implicated in OFDS. Functional studies revealed the involvement of centriole elongation, transition zone and intraflagellar transport defects in OFDS, thus characterising three ciliary protein modules: the complex KIAA0753-FOPNL-OFD1, a regulator of centriole elongation; the Meckel-Gruber syndrome module, a major component of the transition zone; and the CPLANE complex necessary for IFT-A assembly. OFDS now appear to be a distinct subgroup of ciliopathies with wide heterogeneity, which makes the initial classification obsolete. A clinical classification restricted to the three frequent/well-delineated subtypes could be proposed, and for patients who do not fit one of these three main subtypes, a further classification could be based on the genotype

Research and Design of a Routing Protocol in Large-Scale Wireless Sensor Networks

无线传感器网络，作为全球未来十大技术之一，集成了传感器技术、嵌入式计算技术、分布式信息处理和自组织网技术，可实时感知、采集、处理、传输网络分布区域内的各种信息数据，在军事国防、生物医疗、环境监测、抢险救灾、防恐反恐、危险区域远程控制等领域具有十分广阔的应用前景。 本文研究分析了无线传感器网络的已有路由协议，并针对大规模的无线传感器网络设计了一种树状路由协议，它根据节点地址信息来形成路由，从而简化了复杂繁冗的路由表查找和维护，节省了不必要的开销，提高了路由效率，实现了快速有效的数据传输。 为支持此路由协议本文提出了一种自适应动态地址分配算——ADAR（AdaptiveDynamicAddre...As one of the ten high technologies in the future, wireless sensor network, which is the integration of micro-sensors, embedded computing, modern network and Ad Hoc technologies, can apperceive, collect, process and transmit various information data within the region. It can be used in military defense, biomedical, environmental monitoring, disaster relief, counter-terrorism, remote control of haz...学位：工学硕士院系专业：信息科学与技术学院通信工程系_通信与信息系统学号：2332007115216

Quasi-Isometry Classification Of Coarse Hadamard Manifolds

Quasi-conformal mappings were first introduced by L. Ahlfors in 1935, in connection with open Riemann surfaces and value distribution theory, and then studied by O. Teichmuller in 1938. In 1956 A. Beurling and Ahlfors proved an extension theorem which states that a quasi-symmetric map OE : R ! R can be extended to a quasiconformal map of the upper half plane. In 1964 Ahlfors had proven a similar extension theorem for quasi-symmetric mappings of R 2 . Then in 1979 P. Tukia and J. Vaisala proved quasiconformal extension in dimensions 5. The case of extension from 3 to 4 dimensions is still unknown. In this paper we prove three main quasi-conformal extension results. First we prove the Tukia-Vaisala theorem, which states that a quasiconformal map f : R n ! R n can be extended to a quasiconformal map of the upper half space R n+1 + ! R n+1 + , provided n 5: The second result is a similar extension theorem for the strongly uniform domains introduced by Heinonen and Yang in 1993..

MANIFOLDS WHICH CAN NOT BE LEAVES OF FOLIATIONS

The question of when an open manifold is the leaf of a foliation of a compact manifold has been studied for the last twenty years. For open surfaces, this was first addressed by Sondow [Son], and solved by Cantwell and Conlon [CC2] who proved that every complete two manifold can be realized as leaf of a foliation of a compact 3-manifold. In contrast, Ghys [Ghys] and independently T. Inaba, T. Nishimori, M.Takamura and N.Tsuchiya [INTT] constructed open manifolds of dimension 3 which cannot be homotopy equivalent to a leaf of any codimension one topological foliation of a compact manifold, on account of “non-recurrence” properties of their fundamental groups. It is very difficult to obtain non-realization results for this generality, and no such results are known for codimension greater than one. The realization problem can also be formulated to include metric information: given an openmanifoldX and a complete Riemannian metric gX of bounded geometry on TX,thequestionis whether there is a leaf L of a foliation F on a compact Riemannian manifold (V,gV)sothat(X, gX) isquasi-isometric to (L, gL) forth