X染色体的DNA序列结构不同于6、7、8、10、11、12号染色体

雌性哺乳动物X染色体上的大部分基因均因X染色体失活作用而失去表达能力 ,X染色体长臂表现失活更明显。虽然对X染色体失活的许多方面都有所了解 ,但是仍然不清楚失活信号沿着X染色体全长扩散的机制。为了了解X染色体是否有不同于其他染色体的基因组学特征 ,这些特征是否关系到X染色体的失活扩散和维持 ,分析 6、7、8、1 0、1 1、1 2号染色体和X染色体DNA序列 7碱基 (7nt)组合水平的结构是否显示差异。从NCBI基因库(http :∥www .ncbi.nlm .nih .gov genome guide)下载 7条染色体长臂各 6 0Mb区域。将这 6 0Mb区域分为 0 5Mb (或 5 0kb)一段 ,对每一段DNA做 7nt字符串组合分析 ,如 1～ 7,2～ 8,3～ 9…… ,记录每种 7nt字符串的频率 ,A、C、G和T4个硷基的 7nt字符串共有 4 7=1 6 384种组合。根据数字差异显示的结果 (http :∥www .ncbi.nlm .nih .gov genome guide) ,选择在扁桃腺生发中心B细胞中高表达的基因 70个 ,用以计算所有内含子 (有义链 )的 7nt频率值。每个内含子被记录为一组 7nt频率值 ,求和相同基因中的所有内含子相同 7nt字符串的频率值 ,再用该和乘以该基因的表达频率得该基因 7nt字符串的频率值 ,求和 70个基因的 7nt字符串的频率值称做intron 7nt,该值试图模拟细胞中RNA小片段的总和。     

失活X染色体基因逃逸与系统性红斑狼疮的性别二态性

X染色体失活可平衡女性中两条X染色体的基因剂量。越来越多的证据表明,失活X染色体上存在许多能够逃逸失活的基因。逃逸的机制涉及到DNA、RNA、组蛋白的表观修饰以及众多的调控蛋白和染色质的空间结构。失活X染色体基因逃逸的研究为人类疾病(特别是自身免疫性疾病)性别二态性的研究开辟了新的途径。目前已证实包括TLR7、CD40L、IRAK-1、CXCR3、CXorf21等失活X染色体基因逃逸是系统性红斑狼疮(systemic lupus erythematosus,SLE)女性好发的重要原因。本文主要综述了失活X染色体上基因逃逸以及与SLE性别二态性形成的分子机制。阐明SLE性别二态性形成的分子机制,不仅对疾病的诊断、治疗具有重要意义,而且对深入揭示人类免疫系统的发育及调控机理也有重要的理论意义。     

利用相互染色体涂色技术分析两株人肺腺癌细胞系(A549和GLC-82)的核型特征

肺癌是全世界癌症死亡中的一个主要的原因。除吸烟外,一些肺癌患者的发病与氡气污染相关。该研究采用包括染色体分选、正向和反向染色体涂色技术,分析了两株肺腺癌细胞系A549和GLC-82的核型特征。A549和GLC-82细胞系都属于非小细胞肺癌细胞系,但诱因不同,后者来源于一个长期生活在氡气污染环境肺癌病人的癌组织。染色体涂色结果表明,这两株肺癌细胞系发生了复杂的染色体重排。在A549和 GLC-82细胞系中,除正常染色体拷贝数变化外,还分别存在13条和24条畸变染色体。约一半的畸变染色体是通过非相互易位形成的,其余的畸变染色体则是通过一些正常染色体的片段缺失或重复而产生的。尽管这两株肺癌细胞系都没有共同的畸变染色体, 但它们似共享两个染色体易位断裂点：HSA8q24和12q14。     

短间隔连续部分肝切除(SISPH)中糖原、G-6-Pase和RNA变化分析

以 4种短间隔连续部分肝切除模型 (shortintervalsuccessivepartialhepatectomy ,SISPH)为材料 ,分析了连续部分肝切除 (succesivepartialhepatectomy ,SPH)次数和方式对肝糖原和RNA含量和分布及葡萄糖 6 磷酸酶 (G 6 Pase)活性和分布的影响 ,发现 :( 1)上述因素均可显著影响它们的活性或含量和分布 ;( 2 )肝糖原含量变化与G 6 Pase活性无显著相关性。     

蹄蝠科的核型进化:比较染色体涂色、G带和C带分析(英文)

与其姐妹科(菊头蝠科)相比,蹄蝠科的细胞遗传学研究较少。迄今为止,仅少数蹄蝠科几个物种有高分辨率的G带核型报道,且有关该科核型进化的大多数结论都是基于常规Giemsa染色研究而得。该研究利用三叶小蹄蝠的染色体特异探针,通过比较染色体涂色、G和C显带,建立了5种蹄蝠的染色体同源性图谱,并探讨了它们同源染色体间的G和C带异同。结果表明:罗伯逊易位、臂内倒位以及异染色质的扩增可能是蹄蝠科物种核型进化的主要机制。通过对这5种蹄蝠物种及其外群物种之间的同源染色体片段的比较分析,作者推测蹄蝠科的祖先核型并不像先前认为的全由端着丝粒染色体组成,而应该含有中着丝粒染色体。     

Allele Deletion Mapping of the Short Arm of Human Chromosome 3 in Renal Carcinoma

Allelic deletions along the short arm of human chromosome 3 were mapped in 57 pairs of DNA samples from tumor and normal tissue of renal carcinoma patients in order to locate potential tumor suppressor genes. Twenty highly polymorphic microsatellite markers were used for deletion mapping. Allelic deletions were found in most of the samples (91%). Extended terminal deletions (56%) prevailed over shorter internal and multiple deletions and dominated (65%) in the most aggressive histopathological kidney cancer subtype, clear-cell carcinoma. Frequency analysis of loss of heterozygosity allowed detection of the human chromosome 3 regions most essential for renal carcinomas: the region adjacent to the gene VHL(3p26–p25), the region of homozygous deletions AP20 (3p22–p21.33), and a new region between markers D3S2420 and D3S2409 (3p21.31, 2.2 Mbp).     

Complete Genome Sequence of Borrelia afzelii K78 and Comparative Genome Analysis

The main Borrelia species causing Lyme borreliosis in Europe and Asia are Borrelia afzelii, B. garinii, B. burgdorferi and B. bavariensis. This is in contrast to the United States, where infections are exclusively caused by B. burgdorferi. Until to date the genome sequences of four B. afzelii strains, of which only two include the numerous plasmids, are available. In order to further assess the genetic diversity of B. afzelii, the most common species in Europe, responsible for the large variety of clinical manifestations of Lyme borreliosis, we have determined the full genome sequence of the B. afzelii strain K78, a clinical isolate from Austria. The K78 genome contains a linear chromosome (905,949 bp) and 13 plasmids (8 linear and 5 circular) together presenting 1,309 open reading frames of which 496 are located on plasmids. With the exception of lp28-8, all linear replicons in their full length including their telomeres have been sequenced. The comparison with the genomes of the four other B. afzelii strains, ACA-1, PKo, HLJ01 and Tom3107, as well as the one of B. burgdorferi strain B31, confirmed a high degree of conservation within the linear chromosome of B. afzelii, whereas plasmid encoded genes showed a much larger diversity. Since some plasmids present in B. burgdorferi are missing in the B. afzelii genomes, the corresponding virulence factors of B. burgdorferi are found in B. afzelii on other unrelated plasmids. In addition, we have identified a species specific region in the circular plasmid, cp26, which could be used for species determination. Different non-coding RNAs have been located on the B. afzelii K78 genome, which have not previously been annotated in any of the published Borrelia genomes.     

Detailed Comparative Map of Human Chromosome 19q and Related Regions of the Mouse Genome

One of the larger contiguous blocks of mouse–human genomic homology includes the proximal portion of mouse chromosome 7 and the long arm of human chromosome 19. Previous studies have demonstrated the close relationship between the two regions, but have also indicated significant rearrangements in the relative orders of homologous mouse and human genes. Here we present the genetic locations of the homologs of 42 human chromosome 19q markers in the mouse, with an emphasis on genes also included in the human chromosome 19 physical map. Our results demonstrate that despite an overall inversion of sequences relative to the centromere, apparent “transpositions” of three gene-rich segments, and a local inversion of markers mapping near the 19q telomere, gene content, order, and spacing are remarkably well conserved throughout the lengths of these related mouse and human regions. Although most human 19q markers have remained genetically linked in mouse, one small human segment forms a separate region of homology between human chromosome 19q and mouse chromosome 17. Three of the four rearrangements of mouse versus human 19q sequences involve segments that are located directly adjacent to each other in 19q13.3–q13.4, suggesting either the coincident occurrence of these events or their common association with unstable DNA sequences. These data permit an unusually in-depth examination of this large region of mouse–human genomic homology and provide an important new tool to aid in the mapping of genes and associated phenotypes in both species.     

Comparative Genome Analysis of Fish and Human Isolates of Mycobacterium marinum

Mycobacterium marinum is a major causative agent of mycobacteriosis in fish that has a broad range of hosts, including in human isolates. So far, genomic analyses have focused on the human isolate. Here, we compared the draft genome sequences of two strains of M. marinum isolated from fish (MB2 and Europe) with the M. marinum M isolated from humans. M. marinum MB2 and Europe have single, circular chromosomes of 6,134,389 and 6,029,340 bp, and average G + C contents of 65.7 and 65.5 %, respectively. A total of 5,464 coding DNA sequences were annotated in both M. marinum MB2 and Europe genome. Dot plot analyses showed that M. marinum MB2 and Europe were closer to M. marinum M when compared to three other Mycobacterium species. The insertion/deletion gene analysis showed that M. marinum MB2 and Europe contained 342 and 487 genes that were not found in M. marinum M, and lacked 625 and 776 genes found in M. marinum M, respectively. Most of the inserted and deleted genes were classified in the fatty acid, lipid, and isoprenoid subsystem and the virulence, disease, and defense subsystem. Therefore, these results provide insights into the genomic diversity associated with variable hosts and pathogens.     

伪狂犬病病毒Ea株基因组UL区的克隆与序列分析

从伪狂犬病病毒Ea株基因组DNA中扩增到3．76kb的基因组片段,该片段包含UL31、UL32、UL33和UL34基因完整编码区,以及UL30和UL35基因部分序列。UL31、UL32、UL33和UL34基因G C含量为69．5％～73．4％,偏向于使用富含GC特别是第三密码子位置上核苷酸是C或G的密码子,Ala、Leu、Arg的利用率最高,占氨基酸残基总数的36．4％。PRV Ea株UL31和UL32基因与PRV Ka株核苷酸与氨基酸序列同源性都很高,在98％以上;而UL33和UL34基因与Ka株的氨基酸序列同源性较低,分别为95．7％和94．8％。UL31基因在疱疹病毒α—亚科所有成员之间都很保守,并且UL31基因与马疱疹病毒IV型同源程度最高。UL32、UL33和UL34基因均与牛疱疹病毒I型同源程度最高。UL31、UL32、UL33与UL34基因产物均有酪蛋白激酶2磷酸化位点和蛋白激酶C磷酸化位点,表明UL31、UL32、UL33、UL34蛋白质可能都是磷酸化蛋白质。     

伪狂犬病病毒Ea株基因组UL区的克隆与序列分析

从伪狂犬病病毒Ea株基因组DNA中扩增到3.76 kb的基因组片段,该片段包含UL31、UL32、UL33和UL34基因完整编码区,以及UL30和UL35基因部分序列.UL31、UL32、UL33和UL34基因G+C含量为69.5%~73.4%,偏向于使用富含GC特别是第三密码子位置上核苷酸是C或G的密码子,Ala、Leu、Arg的利用率最高,占氨基酸残基总数的36.4%.PRV Ea株UL31和UL32基因与PRV Ka株核苷酸与氨基酸序列同源性都很高,在98%以上;而UL33和UL34基因与Ka株的氨基酸序列同源性较低,分别为95.7%和94.8%.UL31基因在疱疹病毒α-亚科所有成员之间都很保守,并且UL31基因与马疱疹病毒IV型同源程度最高.UL32、UL33和UL34基因均与牛疱疹病毒I型同源程度最高.UL31、UL32、UL33与UL34基因产物均有酪蛋白激酶2磷酸化位点和蛋白激酶C磷酸化位点,表明UL31、UL32、UL33、UL34蛋白质可能都是磷酸化蛋白质.     

Genome Duplications and Other Features in 12 Mb of DNA Sequence from Human Chromosome 16p and 16q

Several publicly funded large-scale sequencing efforts have been initiated with the goal of completing the first reference human genome sequence by the year 2005. Here we present the results of analysis of 11.8 Mb of genomic sequence from chromosome 16. The apparent gene density varies throughout the region, but the number of genes predicted (84) suggests that this is a gene-poor region. This result may also suggest that the total number of human genes is likely to be at the lower end of published estimates. One of the most interesting aspects of this region of the genome is the presence of highly homologous, recently duplicated tracts of sequence distributed throughout the p-arm. Such duplications have implications for mapping and gene analysis as well as the predisposition to recurrent chromosomal structural rearrangements associated with genetic disease.     

Assignment of Three Gene Loci (Pgk, Hgprt, G6pd) to the Long Arm of the Human X Chromosome by Somatic Cell Genetics

The intrachromosomal localization of three X-linked gene loci (PGK, HGPRT and G6PD) has been determined using a somatic cell genetic approach. A human cell line possessing an X/14 translocation was used as one parent in the formation of human/mouse hybrids. The translocation separates the human X into two parts: Xp and t(Xq14q). The data indicate that all three X-linked loci segregate with the t(Xq14q) rearrangement product thus permitting their assignment to the X chromosome's long arm. Secondary rearrangements and data from other laboratories suggest that the order of the the three markers from the centromere to the distal end of the X long arm is PGK, HGPRT, G6PD. It was also observed that NP, an autosomal locus, segregated with the t(Xq14q) chromosome. This provides strong support for the assignment of NP to 14.