叶酸代谢与人类基因组稳定性的关系研究进展

叶酸是人体DNA合成、氨基酸之间相互转化、血红蛋白及肾上腺素、胆碱、肌酸合成所必需的物质。本综述从叶酸的代谢过程、叶酸与肿瘤之间关系、叶酸缺乏引起的分子与生理学效应、亚甲基四氢叶酸还原酶和甲硫氨酸合成酶基因多态性与叶酸代谢的关系等各个方位，综述了叶酸与人类基因组稳定性之间的复杂关系与研究现状。     

叶酸代谢与人类基因组稳定性的关系研究进展

叶酸是人体DNA合成、氨基酸之间相互转化、血红蛋白及肾上腺素、胆碱、肌酸合成所必需的物质。本综述从叶酸的代谢过程、叶酸与肿瘤之间关系、叶酸缺乏引起的分子与生理学效应、亚甲基四氢叶酸还原酶和甲硫氨酸合成酶基因多态性与叶酸代谢的关系等各个方位,综述了叶酸与人类基因组稳定性之间的复杂关系与研究现状。     

对人类胎儿的整个基因组测序

据2012年6月6日Kitzman JO[Sci Transl Med,2012,4（137）：137ra76]报道,用从1例孕妇及12例即将成为父亲的人身上获取的DNA样本重构了一个人类胎儿的全部基因组序列。     

染色体平衡易位影响基因组稳定性的临床研究

目的 探索染色体平衡易位是否影响基因组稳定性。方法 利用回顾性分析将2019年1月至2020年12月在山东大学附属生殖医院行胚胎植入前染色体结构重排检测患者分成两组,实验组为染色体平衡易位携带者来源的异常染色体,对照组为平衡易位携带者的配偶来源的异常染色体,通过单体型分析确认异常胚胎中非易位相关异常染色体的双亲来源,探索平衡易位是否会引起更多染色体异常的发生,从而明确平衡易位对于基因组稳定性的影响。结果 非易位相关染色体片段异常亲本来源分析结果显示,实验组显著高于对照组,即平衡易位携带者来源的片段异常显著高于正常核型来源的片段异常,对于整条染色体异常和嵌合染色体异常,两组无显著性差异。结论 在减数分裂过程中,染色体平衡易位可能是导致染色体片段异常增加的因素之一,最终影响基因组的稳定性。     

人类基因组多样性计划的新动态

自１９９０年１０月１日,人类基因组计划（ｈｕｍａｎｇｅｎｏｍｅｐｒｏｊｅｃｔ,ＨＧＰ）正式启动以来,取得了令人鼓舞的突破性进展,据有关专家估计,将在最初预定的２００５年前完成［１］。随着ＨＧＰ的顺利实施,科学家们又面临着一个新的挑战：人类是一个具有多...     

人类基因组多样性计划-环境基因组计划-药物基因组学

随着人类基因组计划的快速推进,大量基因的发现和大规模序列数据库的建立促使了基因组功能性研究计划启动,如人类基因组多样性计划、环境基因组计划和药物基因组学等。包括这些计划在内的“后基因组计划”将诠释和开发基因组这一宝藏,使人们更好地认识和利用基因组。     

树舌多糖GF对小鼠HepA瘤基因组DNA甲基化影响的实验研究

目的初步探讨树舌多糖GF对小鼠HepA瘤基因组甲基化的影响.方法提取基因组DNA,采用限制性酶切片段长度多态性分析的方法进行甲基化检测.结果 HpaII酶切结果:树舌多糖组可见3个条带,猪苓对照组可见3个条带, 阴性对照组可见4个条带,正常对照组可见2个条带.MspI酶切结果:树舌多糖组可见6个条带,猪苓对照组可见5个条带,阴性对照组可见5个条带,正常对照组可见6个条带.结论小鼠HepA瘤基因组DNA是低甲基化的,树舌多糖GF有阻碍小鼠HepA瘤基因组DNA低甲基化发生的趋势,可能还具有抗5mC的突变的作用.     

人类基因组流行病学及其网络

随着人类基因组研究计划的进展，开展以人群为基础的基因组流行病学研究，建立和完善全球人类基因组流行病学网络，成为国际流行病学研究中的重要课题，有关工作正开始启动。     

人类基因组isochore边界的保守性研究

人类基因组由一些较长的,G+C含量相对均匀的DNA片段组成,也就是我们所说的isochore结构。Isochore结构与许多重要的生物学特征相关,如:基因密度、CpG岛等,关于这些已有系统的研究。我们使用基于Z曲线理论的基因组序列分段算法,在单核苷酸精度的水平上定位了人类基因组56个isochore的边界,共得到79个独立的边界。我们发现在这79个边界中,45.6%的isochore边界在与17个脊椎动物基因组比对时,显示出明显的保守性,比如:某段高保守的序列在isochore边界处转换为一段弱保守或者完全不保守序列。另外isochore边界附近的序列组成高度保守。通过和已被实验证实的复制开关点附近的序列相比较。有理由推断这79个isochore边界都有可能是人类基因组中的复制开关位点,这一点有待实验验证。     

人类和黑猩猩的同一个基因组

据美国BIOCOMPARE科技新闻网（2006／5／22）报道，研究人员一直认为人类基因组上的动态区域，即发生复制和删除的区域，可能与遗传所决定的形态和行为特征之迅速进化有关。     

Age-related changes in genomic stability of horses

Recently, the old horse has been proposed as a model to study telomere-dependent senescence, immunosenescence and inflamm-aging. In the present paper, we used 80 Hucul and Anglo-Arabian horses divided into 3 age groups (juvenile, adult, old) to evaluate age-dependent changes at the genomic and DNA level and in cell proliferative potential. The level of positive TUNEL cells (both apoptotic and with DNA fragmentation), oxidative DNA damage (8-oxoG immunostaining), sister chromatid exchange and bleomycin-induced chromatid breaks were significantly increased in the combined old group compared to the combined adult group. We observed a negative correlation between micronuclei formation and age, which may be associated with damaged cells undergoing apoptosis, rather than expressing micronuclei. We were unable to show any significant changes in the nuclear division index value, which reflects the proliferative status of the viable cell fraction during aging. Here, we show that breed-independent and age-associated changes in genomic stability may contribute, at least in part, to the aging process in the horse.     

Bloom syndrome ortholog HIM-6 maintains genomic stability in C. elegans

Bloom syndrome is caused by mutation of the Bloom helicase (BLM), a member of the RecQ helicase family. Loss of BLM function results in genomic instability that causes a high incidence of cancer. It has been demonstrated that BLM is important for maintaining genomic stability by playing a role in DNA recombination and repair; however, the exact function of BLM is not clearly understood. To determine the mechanism by which BLM controls genomic stability in vivo, we examined the phenotypes caused by mutation of the C. elegans BLM helicase ortholog, HIM-6. We find that the loss of HIM-6 leads to genomic instability as evidenced by an increased number of genomic insertions and deletions, which results in visible random mutant phenotypes. In addition to the mutator phenotype, him-6 mutants have a low brood size, a high incidence of males, a shortened life span, and an increased amount of germ line apoptosis. Upon exposure to high temperature, him-6 mutants that are serially passed become sterile demonstrating a mortal germ line phenotype. Our data suggest a model in which loss of HIM-6 results in genomic instability due to an increased number of DNA lesions, which either cannot be repaired and/or are introduced by low fidelity recombination events. The increased level of genomic instability that leads to him-6(ok412) mutants having a shortened life span.     

基因组重排的机制研究

基因组结构变异是人类基因组中常见的一种变异形式,往往涉及染色体或大片段染色体区域的改变,将原来两个分开的DNA序列重新连接在一起,从而形成染色体片段的缺失、重复复制、插入、倒位或者易位.在核苷酸水平上对大量重排断裂点接头序列特征的分析,为研究基因组重排的机制提供了宝贵的资源.本文综述了导致基因组重排的同源重组和非同源修复机制,并提出复制过程在基因组重排中发挥了重要作用,是细胞压力和结构变异的潜在桥梁,对于理解人类基因组进化和人类疾病的发生发展具有重要意义.     

Impact of inorganic nutrients on maintenance of genomic stability

Maintenance of genome stability is of fundamental importance for counteracting carcinogenesis. Many human genome instability syndromes exhibit a predisposition to cancer. An increasing body of epidemiological evidence has suggested a link between nutrient status and risk of cancer. Like other chemicals, nutrients can be toxic when consumed in excess. It has become clear that both nutritional deficiency and toxicity can compromise the integrity of the genome. This article focuses on roles of inorganic trace nutrients, including selenium, copper, zinc, and iron, in the redox regulation of genome stability and how they relate to the pathologies of genomic instability syndromes and cancer. Environ. Mol. Mutagen. 2009. © 2009 Wiley‐Liss, Inc.     

Prevaccination genomic diversity of human papillomavirus genotype 6 (HPV 6)

Prevaccination genomic diversity of human papillomavirus genotype 6 (HPV 6) was established by sequencing 3798 bp of 77 clinically important HPV 6 isolates obtained from 45 and 32 patients with genital warts and laryngeal papillomas, respectively. By analyzing pooled L1, LCR, E6, E2, and E5 nucleotide data of an individual isolate, a total of 36 different genomic variants were identified, of which six (12 isolates), one (one isolate) and 29 (64 isolates) corresponded to HPV 6b, HPV 6a, and HPV 6vc genetic lineages, respectively. Several novel, potentially important mutations were identified. Non-prototypic HPV 6vc genomic variants were found in the majority of genital warts and laryngeal papillomas included in the study. The presence of serious HPV 6 genome sequence errors was confirmed and novel sequence errors were identified in sequence repositories.     

一种碘化钾提取外周血基因组DNA的方法

目的　建立外周血基因组DNA 的快速提取方法。方法　用碘化钾直接从外周血中提取基因组DNA。结果　用该方法提取的DNA 为大分子量DNA;A260/A280为1.85,A260/A230为2.2;提取效率大于90% ;DNA 体外扩增结果良好。结论　该方法简便、快速、经济,可用于大量临床标本的研究。     

ImprintSeq,a novel tool to interrogate DNA methylation at human imprinted regions and diagnose multilocus imprinting disturbance

PurposeDisruptions of genomic imprinting are associated with congenital imprinting disorders (CIDs) and other disease states, including cancer. CIDs are most often associated with altered methylation at imprinted differentially methylated regions (iDMRs). In some cases, multiple iDMRs are affected causing multilocus imprinting disturbances (MLIDs). The availability of accurate, quantitative, and scalable high-throughput methods to interrogate multiple iDMRs simultaneously would enhance clinical diagnostics and research.MethodsWe report the development of a custom targeted methylation sequencing panel that covered most relevant 63 iDMRs for CIDs and the detection of MLIDs. We tested it in 70 healthy controls and 147 individuals with CIDs. We distinguished loss and gain of methylation per differentially methylated region and classified high and moderate methylation alterations.ResultsAcross a range of CIDs with a variety of molecular mechanisms, ImprintSeq performed at 98.4% sensitivity, 99.9% specificity, and 99.9% accuracy (when compared with previous diagnostic testing). ImprintSeq was highly sensitive for detecting MLIDs and enabled diagnostic criteria for MLID to be proposed. In a child with extreme MLID profile a probable genetic cause was identified.ConclusionImprintSeq provides a novel assay for clinical diagnostic and research studies of CIDs, MLIDs, and the role of disordered imprinting in human disease states.     

同源重组修复与基因组不稳定性

同源重组修复途径极为精确,对于维持基因组的稳定性和完整性至关重要.因此,同源重组修复途径的功能障碍通常会导致严重的基因组不稳定,从而促进肿瘤的发生和演进;但这也可能破坏细胞固有的代谢过程,而成为治疗肿瘤耐药的关键靶点.本文将对同源重组修复的过程、类型及同源重组功能障碍与基因组不稳定性之间的关系加以综述.