一个中国Avellino型角膜营养不良家系的分子遗传学分析

背景研究发现，转化生长因子B诱导（TGFflI）基因是角膜营养不良最常见的致病基因，但rG印，基因突变与患者表型的关系研究目前仍然很少。目的探讨一个中国汉族Avellino角膜营养不良（ACD）家系的临床特征及致病原因，分析TGFfll基因突变与患者表型的关系。方法收集一个中国汉族ACD家系共3代19名家系成员，对现存活的5例患者和13名表型正常成员进行研究，采用裂隙灯显微镜、眼前节OCT、激光扫描共焦显微镜等检查方法观察受检者角膜病变的临床特点。收集所有受检者外周静脉血各2ml，对rG邛，基因进行突变分析和DNA测序。结果先证者诊断为ACD，该家系共6例患者，已去世1例，3代家系中每代均有患病者，男女患病概率相等，遗传模式符合常染色体显性遗传。该家系中3例女性患者角膜混浊病灶的形态呈面包屑样、条索样和点片状，而2例男性患者角膜混浊呈点状；女性患者角膜病变范围大于男性患者；家系中女性患者的视力为0．4～0．9，男性患者视力均为1．0。女性患者和男性患者激光扫描共焦显微镜下和眼前节OCT检查结果均无明显差别。所有患者rG邛，基因中发现第4外显子的C．372G〉A（P．R124H）杂合突变（碱基G〉A），导致第124位的精氨酸变成组氨酸，并发现TGFflI基因8号和12号外显子两个位点存在同义单核苷酸多态性（SNP）（C．981G〉A，V327V和e．1626T〉C，F542F），而家系中表型正常成员未发现此类改变。结论阳邛，基因的R124H突变为该ACD家系的致病突变，该家系中女性患者表型重于男性患者，未发现其与DNA测序结果相关。

用遗传编程进化神经网络结构和权值

本文采用遗传编程(Genetic Programming,下用GP表示)的方法,提出一种对神经网络如何同时优化它的权值和结构(包括层数、每层的神经元个数以及神经元之间的连接关系)的新思想。遗传编程(Genetic Programming)是遗传算法(Genetic Alogrithms)的扩展,利用具有可变长度的LISP符号表达式表示群体中的个体,是基于达尔文(Darwin)的进化论和遗传基因学原理的一种新兴的搜索寻优技术。本文采用这种方法设计了一个神经网络,成功解决了一位加法器问题。

Evaluation of a Novel 32 X-STR Loci Multiplex System in the Forensic Application

The AGCU X Plus STR system is a newly developed multiplex PCR kit that detects 32 X-chromosomal STR loci simultaneously.These are DXS6807,DXS9895,linkage group 1(DXS10148,DXS10135,DXS8378),DXS9902,DXS6795,DXS6810,DXS10159,DXS10162,DXS10164,DXS7132,linkage group 2(DXS10079,DXS10074,DXS10075),DXS981,DXS6800,DXS6803,DXS6809,DXS6789,DXS7424,DXS101,DXS7133,GATA172D05,GATA165B12,linkage group 3(DXS10103,HPRTB,DXS10101),GATA31E08 and linkage group 4(DXS8377,DXS10134,DXS7423).A major advantage of this kit is that it takes into account linkage between loci,in addition to detecting more X-STR loci.In order to evaluate the forensic application of 32 X-STR fl uorescence amplifi cation system,PCR settings,sensitivity,species specifi city,stability,DNA mixtures,concordance,stutter,sizing precision,and population genetics investigation were evaluated according to the Scientific Working Group on DNA Analysis Methods(SWGDAM)developmental validation guidelines.The study showed that the genotyping results of each locus were signifi cantly accurate when the DNA template was at least 62.5 pg.Complete profi les were obtained for the 1∶1 and 1∶3 combinations.A total of 209 unrelated individuals from Southern Chinese Han community,consisting of 84 females and 125 males,were selected for population studies,and 285 allele profi les were detected from 32 X-STR loci.The polymorphism information content(PIC)ranged from 0.2721 in DXS6800,to 0.9105 in DXS10135,with an average of 0.6798.DXS10135(PIC=0.9105)was the most polymorphic locus,with discrimination power(DP)of 0.9164 and 0.9871 for the male and female.The cumulative PD_(F),PD_(M),MEC_(trio) and MEC_(duo) valu es were all greater than 0.999999999.There were 78 different DXS10103-HPRTB-DXS10101 haplotypes among the 125 males,and the haplotype diversity was 0.9810.There was no signifi cant difference in the cumulative PD_(F),PD_(M),MEC_(trio) and MEC_(duo) values whether considering linkage or not.In summary,the new X-STR multiplex typing system is effective and reliable,which can be useful in human genetic analysis and kinship testing as a potent complement to autosomal STR typing.

Cytological and Molecular Identification of Alien Chromatin in Giant Spike Wheat Germplasm

Alien chromosomes of twelve giant spike wheat germplasm lines were identified by C-banding, genomic in situ hybridization (GISH), sequence characterized amplified region (SCAR), and random amplified polymorphic DNA (RAPD). All lines showed a chromosome number of 2n = 42, five of them carried both a pair of wheat-rye (Triticum aestivum-Secale cereal) 1BL/1RS translocation chromosomes and a pair of Agropyron intermedium (Ai) chromosomes, three carried a pair of Ai chromosomes only, three others carried a pair of 1BL/1RS chromosomes only, and one carried neither 1BL/1BS nor Ai chromosome. Further identification revealed that the identical Ai chromosome in these germplasm lines substituted the chromosome 2D of common wheat (T aestivum L.), designated as 2Ai. The genetic implication and further utilization of 2Ai in wheat improvement were also discussed.

Construction of retroviral vector carrying HSV tk gene under control of human AFP enhancer core sequence and human pgk promotor *

AIM Tenstruct retroviral vector bringing HSV tk gene under control by human AFP enhancer core sequence and human pgk promotor.

“成都美”:中国美女第一城

全中国什么地方的女孩最美?哪里的美女比例最高?美女决定论决定了美女的产生。从中国古代哲学考量,"时空决定论"是天时,"地理决定论""气候决定论"是地利,"基因决定论""文化决定论"是人和。具备上述诸要素的区域女性可以说是很标准的美了。成都美女完全具备上述"天时、地利、人和"的三大要素,此外,她们更具有一个要素,那就是"美食决定论",可以将其归为"己和"。可见,虽然美女的界定是一个非常复杂的动态过程,但如果将美女的外在美和内在美,造成美女的自然地理因素、历史人文元素、科技元素等综合考量,成都应该是中国美女第一城。

Genetics of hepatocellular carcinoma

The completely assembled human genome has made it possible for modern medicine to step into an era rich in genetic information and high-throughput genomic analysis. These novel and readily available genetic resources and analytical tools may be the key to unravel the molecular basis of hepatocellular carcinoma (HCC). Moreover, since an efficient treatment for this disease is lacking, further understanding of the genetic background of HCC will be crucial in order to develop new therapies aimed at selected targets. We report on the current status and recent developments in HCC genetics. Special emphasis is given to the genetics and regulation of major signalling pathways involved in HCC such as p53, Wnt- signalling, TGFβ, Ras, and Rb pathways. Furthermore, we describe the influence of chromosomal aberrations as well as of DNA methylation. Finally, we report on the rapidly developing field of genomic expression profiling in HCC, mainly by microarray analysis.

IL-17RD （Sef or IL-17RLM） interacts with IL-17 receptor and mediates IL-17 signaling

Interleukin-17 （IL-17 or IL-17A） production is a hallmark of TH17 cells, a new unique lineage of CD4^＋ T lymphocytes contributing to the pathogenesis of multiple autoimmune and inflammatory diseases. IL-17 receptor （IL-17R or IL-17RA） is essential for IL-17 biological activity. Emerging data suggest that the formation of a heteromeric and/or homomeric receptor complex is required for IL-17 signaling. Here we show that the orphan receptor IL-17RD （Sef, similar expression to FGF genes or IL-17RLM） is associated and colocalized with IL-17R. Importantly, IL-17RD mediates IL-17 signaling, as evaluated using a luciferase reporter driven by the native promoter of 24p3, an IL-17 target gene. In addition, an IL-17RD mutant lacking the intraeellnlar domain dominant-negatively suppresses IL-17R- mediated IL-17 signaling. Moreover, IL-17RD as well as IL-17R is associated with TRAF6, an IL-17R downstream molecule. These results indicate that IL-17RD is a part of the IL-17 receptor signaling complex, therefore providing novel evidence for IL-17 signaling through a heteromeric and/or homomeric receptor complex.

PTEN： a default gate-keeping tumor suppressor with a versatile tail

The tumor suppressor PTEN controls a variety of biological processes including cell proliferation, growth, migration, and death. As a master cellular regulator, PTEN itself is also subjected to deliberated regulation to ensure its proper function. Defects in PTEN regulation have a profound impact on carcinogenesis. In this review, we briefly discuss recent advances concerning PTEN regulation and how such knowledge facilitates our understanding and further exploration of PTEN biology. The carboxyl-tail of PTEN, which appears to be associated with multiple types of posttranslational regulation, will be under detailed scrutiny. Further, a comparative analysis of PTEN and p53 suggests while p53 needs to be activated to suppress tumorigenesis （a dormant gatekeeper）, PTEN is probably a constitutive surveillant against cancer development, thus a default gatekeeper.

Application of cDNA array for studying the gene expression profile of mature appressoria of Magnaporthe grisea

Appressorium is an infection structure of the phytopathogenic fungus Magnaporthe grisea. Analysis of gene expression profiles ofappressorium development provides insight into the molecular basis of pathogenicity and control of this fungal plant disease. A cDNA array representing 2927 unique genes based on a large EST （expressed sequence tag） database ofM. grisea strain Y34 was constructed and used to profile the gene expression patterns at mycelium and appressorium maturation stages. Compared with mycelia, 55 up-regulated and 22 down-regulated genes were identified in mature appressoria. Among 77 genes, 16 genes showed no similarity to the genome sequences of M. grisea. A novel homologue of peptidyl-prolyl cis-trans isomerase was found to be expressed at low-level in mature appressoria of M. grisea. The results indicated that the genes such as pyruvate carboxylase, phospholipid metabolism-related protein and glyceraldehyde 3-phosphate dehydrogenase involved in gluconeogenesis, lipid metabolism and glycolysis, showed differential expression in mature appressoria. Furthermore, genes such as PTHll, beta subunit of G protein and SGTI involved in cell signalling, were expressed differentially in mature appressoria. Northern blot analysis was used to confirm the cDNA array results.

Functional characterization of the human-specific （type II） form of kallikrein 8, a gene involved in learning and memory

Kallikrein 8 （KLK8） is a serine protease functioning in the central nervous system, and essential in many aspects of neuronal activities. Sequence comparison and gene expression analysis among diverse primate species identified a human-specific splice form of KLK8 （type II） with preferential expression in the human brain, which may contribute to the origin of human cognition. To gain insights into the physiological and biochemical role of this novel form, we conducted functional analyses of human type II KLK8. Our results show that type II KLK8 is abundantly expressed in human embryonic stem cells and in embryo brain samples, suggesting a potential role in embryogenesis. There are dramatic expression variations in different individuals and brain regions, which is a reflection of its dynamic role in neural activities. Furthermore, the transcription start site （TSS） of KLK8 is tissue-specific, with a brain-specific TSS found in humans indicating functional specialization. Our in vitro biochemical assay shows that there is a type II-specific intermediate protein form, although the processed end-point enzymes are the same for both type 1 and type II KLK8, suggesting that the emergence of type II KLK8 in the human brain likciy leads to functional modifications of KLK8.

STUDY OF LOSS OF HETEROZYGOSITY AT DCC AND APC/MCC GENETIC LOCI OF GASTRIC CANCER

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Genetic interactions and modifi er genes in Hirschsprung's disease

Hirschsprung's disease is a congenital disorder that occurs in 1:5000 live births. It is characterised by an absence of enteric neurons along a variable region of the gastrointestinal tract. Hirschsprung's disease is classified as a multigenic disorder, because the same phenotype is associated with mutations in multiple distinct genes. Furthermore, the genetics of Hirschsprung's disease are highly complex and not strictly Mendelian. The phenotypic variability and incomplete penetrance observed in Hirschsprung' s disease also suggests the involvement of modifier genes. Here, we summarise the current knowledge of the genetics underlying Hirschsprung's disease based on human and animal studies, focusing on the principal causative genes, their interactions, and the role of modif ier genes.

Genetic instability of BRCA1 gene at locus D17S855 is related to clinicopathological behaviors of gastric cancer from Chinese population

AIM： To investigate genetic instability of gene BRCA1 at locus D17S855, and their relationship with clinicopathological characteristics of gastric cancer in Chinese population. METHODS： Microsatellite instability （MSI） and loss of heterozygosity （LOH） of gene BRCA1 at locus D17S855 were compared between 37 samples of gastric cancer and corresponding non-cancerous gastric tissue. RESULTS： MSI at locus D17S855 was positive in 7 of 37 samples of gastric cancer （18.95%）. MSI had a close relationship with TNM staging but no relation with lymph node metastasis, histological type or tumor differentiation. MSI positive frequency in TNM Ⅰ ＋ Ⅱ （31.58%, 6/19） was much higher than that in TNM Ⅲ＋ Ⅳ （5.56%, 1/18）, （P 〈 0.05）. LOH positive rate was 18.92% （7/37）. LOH had no relationship to histological type, tumor differentiation or lymph node metastasis, but LOH positive rate in TNM Ⅲ＋ Ⅳ was 33.33% （6/18）, much higher than that in TNM Ⅰ ＋ Ⅱ （ 5.26%, 1/19）, （P 〈 0.05）. BRCA1 protein was expressed in 14 of 37 samples of gastric cancer. The positive rates of BRCA1 protein in TNM Ⅰ ＋ Ⅱ and TNM Ⅲ＋ Ⅳ were 57.89% and 16.67%, respectively, （P 〈 0.05）. The positive rate of BRCA1 protein was 77.78% in high differentiation samples, 30.77% in middle differentiation and 12.50% in lower differentiation samples, （P 〈 0.05）. CONCLUSION： MSI of BRCA1 gene could be used as a molecular marker in early phases of sporadic gastric cancer in Chinese population. LOH occurs at later period of gastric cancer, therefore, it could be used as prognostic factor.

Short Review:Mitochondrion and its related disorders:Making a comeback

The great majority of genetic disorders are caused by defects in the nuclear genome. However, some significant diseases are the result of mitochondrial mutations. Because of the unique features of the mitochondria, these diseases display characteristic modes of inheritance and a large degree of phenotypic variability. Recent studies have suggested that mitochondrial dysfunction plays a central role in a wide range of age-related disorders and various forms of cancer.

Study of Resistin gene expression in peripheral blood mononuclear cell and its gene polymorphism in a small range population

Objective: To observe the expression of Resistin mRNA in peripheral blood mononuclear cells and its gene poly-morphism in coding region in a small range population in Zhejiang Province of China. Methods: Eighty-three cases of type 2 diabetes mellitus and 53 healthy people were included. The expression of Resistin mRNA in peripheral blood mononuclear cells was detected by RT-PCR and semi-quantitative PCR assay. The sequencing work was done in Resistin cDNA and gene poly-morphism was analyzed. Results: At the same condition, in 83 diabetes patients, Resistin mRNA was detected in 23 cases (11 males and 12 females). There was no Resistin mRNA expression in 53 healthy people. The ratio of PCR products between Resistin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was from 0.564 to 1.238, averaging 0.804±0.436. The sequence of Resistin cDNA is almost identical with each other and with that in GenBank with no single nucleotide polymorphism being found. Conclusion: Resistin mRNA is expressed in human peripheral blood mononuclear cells in some type 2 diabetes mellitus, but its expression is at a low level. Among the experiment population we did not find polymorphism phenomenon in Resistin coding region. The different individual’s Resistin coding region is highly coincident.

Investigations and thoughts of the ethics in genetic discrimination

A questionnaire research in ethics was conducted to get the view of students of medical universities in Shanghai on genomics and genetic discrimination. We find that 66% respondents indicated their willingness to understand the genetic information and 79% of respondents mind their own genetic information be aware of by other people. In contrast, 77% of the respondents believe that medical organization are not able to protect personal genetic information from disclose. Hence, it is significant to take some measures to preserve citizen's genetic information privacy. Depending on our results, we put forward our suggestion to this problem.

Genomic analysis of epithelial ovarian cancer

Ovarian cancer is a major health problem for women in the United States. Despite evidence of considerable heterogeneity, most cases of ovarian cancer are treated in a similar fashion. The molecular basis for the clinicopathologic characteristics of these tumors remains poorly defined. Whole genome expression profiling is a genomic tool, which can identify dysregulated genes and uncover unique sub-classes of tumors. The application of this technology to ovarian cancer has provided a solid molecular basis for differences in histology and grade of ovarian tumors. Differentially expressed genes identified pathways implicated in cell proliferation, invasion, motility, chromosomal instability, and gene silencing and provided new insights into the origin and potential treatment of these cancers. The added knowledge provided by global gene expression profiling should allow for a more rational treatment of ovarian cancers. These techniques are leading to a paradigm shift from empirical treatment to an individually tailored approach. This review summarizes the new genomic data on epithelial ovarian cancers of different histology and grade and the impact it will have on our understanding and treatment of this disease.

Research on Oxalate Oxidase and Its Genes in Plants

This paper introduces the discovery,composition and structure of oxalate oxidase,as well as illustrates the biological functions of this enzyme.With a comprehensive introduction upon previous researches upon gene cloning and heredity transformation of this enzyme,it indicates that heredity transformation can increase the content of oxalate oxidase within the plants and also enhance their resistance.The paper also points out the problems such as lack of gene resources and difficulty in the transformation of heterologous genes,and the focus in later researches should be laid upon the exploration of plant resources relative to this enzyme and selection of resistant species.

Using genetic markers in unpedigreed populations to detect a heritable trait

Before a breeder invests selection pressure on a trait of interest, it needs to be established whether that trait is actually heritable. Some traits may not have been measured widely in pedigreed populations, for example, a disease or deformity may become more prevalent than previously, but is still relatively rare. One approach to detect inheritance would be to screen a commercial population to obtain a sample of "affecteds" (the test group) and to also obtain a random control group. These indi- viduals are then genotyped with a set of genetic markers and the relationships between individuals within each group estimated. If the relatedness is higher in the test group than in the control group, this provides initial evidence for the trait being heritable. A power simulation shows that this approach is feasible with moderate resources.