Development of genetic research in the USSR

Two periods of the development of genetic research in the USSR with reference to its current trends of plant and animal genetics, cytogenetics, and molecular genetics are reviewed. A short list of priority areas is established: the maintenance and use of unique gene pools of plants and animals; the domestication of animals and cultivation of new plants; the development of programmes for mathematical treatment of genetic data banks. It is suggested to consider them within the framework of international projects. The idea is to promote the collaborative efforts of scientists on an international scale.     

FISH在人类未受精卵染色体异常分析中的应用

分子细胞遗传学的主要技术代表———荧光原位杂交 (FISH)是用荧光标记的依靠探针杂交原理在细胞核中或染色体上显示某一特定核酸序列的位置 ,并可进行相对定量分析 .它广泛应用于遗传病的诊断、产前诊断、肿瘤遗传学、进化遗传学研究和基因定位等领域 ,随着辅助生殖技术的进展 ,将在植入前胚胎遗传学诊断 (PGD)、生殖细胞 (卵母细胞和精子 )染色体异常的研究方面发挥更大的用途 .它是联系分子遗传学和细胞遗传学之间的桥梁 .     

Fluorescence in situ hybridization (FISH)--application in research and diagnostics

The methods of molecular cytogenetics, in particular fluorescence in situ hybridization (FISH), are widely applied in cytogenetics for identification of numerical and structural chromosomal abnormalities, which are difficult to detect by routine cytogenetic techniques. Due to many advantages, FISH is used in research (gene mapping, gene expression studies, interspecies chromosome homology), and clinical diagnostics (chromosomal aberrations analysis in pre- and postnatal diagnostics, oncology). The techniques of in situ hybridization (ISH) are often employed in addition to classical banding techniques, in case where banding pattern is not reliable. This paper focuses on particular clinical examples, where FISH was successfully used to identify structural and numerical chromosomal aberrations.     

A Predictive Framework for Integrating Disparate Genomic Data Types Using Sample-Specific Gene Set Enrichment Analysis and Multi-Task Learning

Understanding the root molecular and genetic causes driving complex traits is a fundamental challenge in genomics and genetics. Numerous studies have used variation in gene expression to understand complex traits, but the underlying genomic variation that contributes to these expression changes is not well understood. In this study, we developed a framework to integrate gene expression and genotype data to identify biological differences between samples from opposing complex trait classes that are driven by expression changes and genotypic variation. This framework utilizes pathway analysis and multi-task learning to build a predictive model and discover pathways relevant to the complex trait of interest. We simulated expression and genotype data to test the predictive ability of our framework and to measure how well it uncovered pathways with genes both differentially expressed and genetically associated with a complex trait. We found that the predictive performance of the multi-task model was comparable to other similar methods. Also, methods like multi-task learning that considered enrichment analysis scores from both data sets found pathways with both genetic and expression differences related to the phenotype. We used our framework to analyze differences between estrogen receptor (ER) positive and negative breast cancer samples. An analysis of the top 15 gene sets from the multi-task model showed they were all related to estrogen, steroids, cell signaling, or the cell cycle. Although our study suggests that multi-task learning does not enhance predictive accuracy, the models generated by our framework do provide valuable biological pathway knowledge for complex traits.     

Early studies on human chromosomes

The author describes his introduction to the field of cytogenetics, with his first viewing of himself, cytogenetically, down the microscope, and the progression of human cytogenetics as an area of study up to its modern integration with molecular genetics and computer technology.     

Education and certification of genetic counselors.

Genetic counseling is defined by the American Society of Human Genetics as a communication process which deals with the human problems associated with the occurrence, or risk of occurrence, of a genetic disorder in a family. The first graduate program (Master's degree) in genetic counseling started in 1969 at Sarah Lawrence College, NY, USA, while in 1979 the National Society of Genetic Counseling (NSGC) was established. Today, there are 29 programs in U.S.A. offering a Master's degree in Genetic Counseling, five programs in Canada, one in Mexico, one in England and one in S. Africa. Most of these graduate programs offer two year training, consisting of graduate courses, seminars, research and practical training. Emphasis is given in human physiology, biochemistry, clinical genetics, cytogenetics, molecular and biochemical genetics, population genetics and statistics, prenatal diagnosis, teratology and genetic counseling in relation to psychosocial and ethical issues. Certification for eligible candidates is available through the American Board of Medical Genetics (ABMG). Requirements for certification include a master's degree in human genetics, training at sites accredited by the ABMG, documentation of genetic counseling experience, evidence of continuing education and successful completion of a comprehensive ABMG certification examination. As professionals, genetic counselors should maintain expertise, should insure mechanisms for professional advancement and should always maintain the ability to approach their patients.     

Integrative genomics of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a complex disease with both environmental and genetic determinants, the most important of which is cigarette smoking. There is marked heterogeneity in the development of COPD among persons with similar cigarette smoking histories, which is likely partially explained by genetic variation. Genomic approaches such as genomewide association studies and gene expression studies have been used to discover genes and molecular pathways involved in COPD pathogenesis; however, these “first generation” omics studies have limitations. Integrative genomic studies are emerging which can combine genomic datasets to further examine the molecular underpinnings of COPD. Future research in COPD genetics will likely use network-based approaches to integrate multiple genomic data types in order to model the complex molecular interactions involved in COPD pathogenesis. This article reviews the genomic research to date and offers a vision for the future of integrative genomic research in COPD.     

Biology of advanced uveal melanoma and next steps for clinical therapeutics

Uveal melanoma is the most common intraocular malignancy although it is a rare subset of all melanomas. Uveal melanoma has distinct biology relative to cutaneous melanoma, with widely divergent patient outcomes. Patients diagnosed with a primary uveal melanoma can be stratified for risk of metastasis by cytogenetics or gene expression profiling, with approximately half of patients developing metastatic disease, predominately hepatic in location, over a 15‐yr period. Historically, no systemic therapy has been associated with a clear clinical benefit for patients with advanced disease, and median survival remains poor. Here, as a joint effort between the Melanoma Research Foundation's ocular melanoma initiative, CURE OM and the National Cancer Institute, the current understanding of the molecular and immunobiology of uveal melanoma is reviewed, and on‐going laboratory research into the disease is highlighted. Finally, recent investigations relevant to clinical management via targeted and immunotherpies are reviewed, and next steps in the development of clinical therapeutics are discussed.     

Understanding the classics: the unifying concepts of transgressive segregation,inbreeding depression and heterosis and their central relevance for crop breeding

Transgressive segregation and heterosis are the reasons that plant breeding works. Molecular explanations for both phenomena have been suggested and play a contributing role. However, it is often overlooked by molecular genetic researchers that transgressive segregation and heterosis are most simply explained by dispersion of favorable alleles. Therefore, advances in molecular biology will deliver the most impact on plant breeding when integrated with sources of heritable trait variation – and this will be best achieved within a quantitative genetics framework. An example of the power of quantitative approaches is the implementation of genomic selection, which has recently revolutionized animal breeding. Genomic selection is now being applied to both hybrid and inbred crops and is likely to be the major source of improvement in plant breeding practice over the next decade. Breeders’ ability to efficiently apply genomic selection methodologies is due to recent technology advances in genotyping and sequencing. Furthermore, targeted integration of additional molecular data (such as gene expression, gene copy number and methylation status) into genomic prediction models may increase their performance. In this review, we discuss and contextualize a suite of established quantitative genetics themes relating to hybrid vigour, transgressive segregation and their central relevance to plant breeding, with the aim of informing crop researchers outside of the quantitative genetics discipline of their relevance and importance to crop improvement. Better understanding between molecular and quantitative disciplines will increase the potential for further improvements in plant breeding methodologies and so help underpin future food security.     

巴氏小体案例在遗传学教学中的应用

细胞遗传学在染色体水平上有3个经典问题,即巴氏小体、多线染色体和灯刷染色体的形成机制和遗传学效应。其中巴氏小体因其与哺乳动物在两性间X染色体的剂量补偿效应、人类性别鉴定和某些人类疾病的相关性而引起科研和教学工作者的持续关注。在遗传学教学过程中,作者尝试将国外的案例教学方式引入教学实践,将巴氏小体这一经典遗传学问题作为一条线贯穿于遗传学教学的部分环节,例如伴性遗传、基因表达调控、癌症发生以及遗传学实验,最后通过课堂讨论会的形式全面总结相关的遗传学知识。结果发现,这种改进的教学方法不仅可以优化遗传学教学内容,拓宽并巩固学生的遗传学基础知识,形成了对一个经典遗传学问题的系统观、发展观;还能引导和激发学生对生命科学的兴趣,收到了良好的教学效果。     

Application of the Barr body case in teaching practice of genetics

There are three classical problems at the chromosome level in cytogenetics, namely the formation mechanisms and effects of Barr body, polytenic chromosome, and lampbrush chromosome. Teachers and researchers keep sustaining attention to the Barr body because of the relationships between Barr body and the X chromosome dosage compensation effect in mammals, the human sex identification, and some human diseases. In our genetics teaching practice, we tried the case-based teaching method. We introduced the classical problems and research progress of the Barr body, as a line, into partial sections of our genetics teaching contents such as sex-linked genetic analysis, eukaryotic gene expression regulation, cancer genetic analysis, and genetic experiments. Finally, it will form a comprehensive summary of related knowledge of genetics through class discussion on the Barr body. We found that this teaching method can not only optimize the teaching contents of genetics, consolidate and widen students' basic knowledge, and help student to form the systemic and developmental views of a classical genetics problem, but also inspire students' interest in life sciences. Good teaching results have been achieved.     

Dissecting the molecular mechanisms of cancer through bioinformatics-based experimental approaches

Cancer is a disease of aberrant gene expression characterized by inappropriate (temporal or quantitative) expression of positive mediators of cell proliferation in conjunction with diminished expression of negative mediators of cell growth. Alteration of the normal balance of these positive and negative mediators leads to the abnormal growth of cells and tissues that typify neoplastic disease. Development of a better understanding of the genetic and epigenetic mechanisms that induce neoplastic transformation and drive the cancer phenotype is essential for continued progress towards the design of practical molecular diagnostics and effective treatment strategies. Over the past decades, molecular techniques that facilitate the assessment of gene expression, identification of gene mutations, and characterization of chromosome abnormalities (numeric and structural) have been established and applied to cancer research. However, many of these techniques are slow and labor-intensive. More recently, high-throughput technologies have emerged that generate large volumes of data related to the genetics and epigenetics of cancer (or other disorders). These advances in molecular genetic technology required the development of sophisticated bioinformatic tools to manage the large datasets generated. The combination of high-throughput molecular assays and bioinformatic-based data mining strategies has significantly impacted our understanding of the molecular pathogenesis of cancer, classification of tumors, and now the management of cancer patients in the clinic. This article will review basic molecular techniques and bioinformatic-based experimental approaches used to dissect the molecular mechanisms of carcinogenesis.     

Systems genetics in “-omics” era: current and future development

The systems genetics is an emerging discipline that integrates high-throughput expression profiling technology and systems biology approaches for revealing the molecular mechanism of complex traits, and will improve our understanding of gene functions in the biochemical pathway and genetic interactions between biological molecules. With the rapid advances of microarray analysis technologies, bioinformatics is extensively used in the studies of gene functions, SNP–SNP genetic interactions, LD block–block interactions, miRNA–mRNA interactions, DNA–protein interactions, protein–protein interactions, and functional mapping for LD blocks. Based on bioinformatics panel, which can integrate “-omics” datasets to extract systems knowledge and useful information for explaining the molecular mechanism of complex traits, systems genetics is all about to enhance our understanding of biological processes. Systems biology has provided systems level recognition of various biological phenomena, and constructed the scientific background for the development of systems genetics. In addition, the next-generation sequencing technology and post-genome wide association studies empower the discovery of new gene and rare variants. The integration of different strategies will help to propose novel hypothesis and perfect the theoretical framework of systems genetics, which will make contribution to the future development of systems genetics, and open up a whole new area of genetics.     

生物技术用于黄瓜遗传育种

“十五”期间,生物技术在黄瓜遗传育种上的应用更加广泛,分子标记辅助育种、单倍体育种以及黄瓜基因工程改良取得了重要进展。本文综述了黄瓜基因分子标记、遗传图谱构建、基因定位、基因克隆与表达、品种DNA指纹图谱分析、分子技术鉴定病害、单倍体和三倍体培养、遗传转化体系建立及基因工程改良方面的最新进展,并讨论了存在的问题和前景。     

Application of Molecular Biology and Genetics in Endocrinology

ObjectiveTo review the growing impact of molecular biology and genetics on clinical endocrinology.MethodsMedical literature, databases, and Web sites describing genetics and genomic medicine with relevance for clinical endocrinology were reviewed.ResultsMany monogenic disorders can now be explained at the molecular level and the diagnosis can be established through mutational analysis. The ability to establish a molecular diagnosis is relevant for carrier detection and genetic counseling. In contrast to the significant advances in monogenic disorders, the current knowledge about the genetic components contributing to the pathogenesis of complex disorders is still relatively modest and is a major focus of current research efforts. Molecular biology already has an important impact on therapy in endocrine disorders. A broad spectrum of recombinant peptides and proteins are used in daily practice, eg, insulin and insulin analogues. Moreover, the increasingly detailed understanding of the molecular pathogenesis of cancer is leading to the development of novel and more specific inhibitors. While genetic testing has many advantages, it is important that physicians and patients are aware of potential limitations. They include, among others, technical limitations and allelic and nonallelic heterogeneity. These limitations need to be discussed in detail with patients and relatives, and it is often useful to involve a genetic counselor before obtaining informed consent by the individuals undergoing testing.ConclusionMolecular biology and genetics play an increasingly important role for the diagnosis and therapy of endocrine disorders. Challenges for the future include the elucidation of the genetic components contributing to complex disorders, eg, diabetes mellitus type 2, and the development of cheaper and comprehensive DNA sequencing technologies. Lastly, it is important that there is continuing attention directed towards the ethical, social, and legal aspects surrounding genetic medicine. (Endocr Pract, 2007;13: 534-541)     

Clinical impact of molecular diagnostics in endocrinology. Polymorphisms,mutations and DNA technologies

Genetic defects in genes encoding hormones, hormone receptors or polypeptides of the signaling pathways usually cause complex disease manifestations characterized by the involvement of several tissues and variable expression. Genetic aberrations, like chromosome aneuploidy, gene translocations or mutations in key regulatory proteins (even if not directly affecting genes of the endocrine system) often lead to clinical symptoms, including central endocrine functions like sexual differentiation or metabolic disturbances, like diabetes mellitus. But also minor genetic alterations like point mutations can affect the function of gene products to cause endocrine diseases. If the underlying molecular defects of endocrinopathies are known, direct molecular diagnosis can be performed. This is particularly useful if it helps to solve difficult differential diagnosis problems or if there exist effective preventive therapeutic options. The present paper presents examples for endocrine diseases in which molecular testing significantly increases the specificity and sensitivity of diagnostics and demonstrates the benefits for the patients and the healthcare system. In multiple endocrine neoplasia type 2, an unambiguous identification of gene carriers in affected families can be achieved by genetic testing. As a preventive measure to avoid medullary thyroid carcinoma, prophylactic thyroidectomy is recommended for individuals carrying the disease causing mutation. In adrenogenital syndrome, sequence analysis of the steroid 21-hydroxylase gene has become an important tool to confirm or exclude suspected late-onset forms of the disease, where hormone measurements are not informative. The major benefit, however, lies in identifying heterozygous carriers and providing a reliable prenatal test for couples carrying a defect in the 21-hydroxylase gene. Today, prenatal treatment with dexamethasone, which prevents the virilization in female fetuses, should always be based on results from molecular diagnosis performed from chorionic villus samples.     

Localizing DNA and RNA within nuclei and chromosomes by fluorescence in situ hybridization.

The enormous potential of in situ hybridization derives from the unique ability of this approach to directly couple cytological and molecular information. In recent years, there has been a surge of success in powerful new applications, resulting from methodologic advances that bring the practical capabilities of this technology closer to its theoretical potential. A major advance has been improvements that enable, with a high degree of reproducibility and efficiency, precise visualization of single sequences within individual metaphase and interphase cells. This has implications for gene mapping, the analysis of nuclear organization, clinical cytogenetics, virology, and studies of gene expression. This article discusses the current state of the art of fluorescence in situ hybridization, with emphasis on applications to human genetics, but including brief discussions on studies of nuclear DNA and RNA organization, and on applications to clinical genetics and virology. Although a review of all of the literature in this field is not possible here, many of the major contributions are summarized along with recent work from our laboratory.     

优生与遗传咨询的临床研究

总结本室优生遗传咨询门诊万例病例资料,应用细胞学方法、荧光原位杂交法和分子遗传学PCR方法检出外周血染色体异常率10.30%（555/5390）,产前诊断核型异常率为6.68%（145/2171）,胎停育绒毛核型异常率45.16%（28/62）,总检出率为9.55%;PCR检测178例,正常人155例,患者23例;FISH结果：性别Y检测5例,21-三体征检测6例,均阳性。传统细胞学方法为染色体病诊断不可替代的重要手段;分子遗传学PCR方法及FISH检测方便、快速、精确,值得推广;遗传咨询,遗传病检测及产前诊断,对降低患儿出生率具有重大意义。 Clinical Research of Genetic Counseling WANG Shu-yu,WANG Su-gui,REN Guo-qing,JIA Chan-wei,MA Yan-min,XUE Hong Capital Medical University Beijing OB/GYN Hospital,Beijing 100006,China Abstract:To supply reliable materials for the assessment of recurrence risk,prenatal diagnosis and the supervision of high risk persons,we analyzed 10811 patients with the methods of cytogenetics,fluorescent in situ hybridization and molecular genetic PCR methods.The result of cytogenetics:there were 555 abnormal karyotypes of peripheral blood on 5390 cases (10.30%);In 2171 patients who asked for prenatal diagnosis,145 abnormal karyotypes were found (6.68%);We also karyotyped chorionic villous cells of 62 patients with spontaneous abortion and found 28 abnormal karyotypes (45.16%).The PCR results of 23 patients with Down's syndrome were all positive while the results of 155 normal persons were all negative.The method of cytogenetics is very important for diagnosis of abnormal karyotypes;Molecular genetic methods by PCR and FISH are quick,convenient and applicable way. Key words：genetic counseling; prenatal diagnosis; karyotypes abnormal; molecular genetics     

Integrating genetic and parasitological approaches in the frame of multidisciplinary fish stock analysis

To assess fish stocks boundaries and state, the tools of population genetics have been widely used, contributing to the evaluation of relevant parameters such as the identification of stock boundaries, the assessment of gene flow and the estimation of effective population size. Also, increasing evidences show that the monitoring of the genetic diversity level is a reliable method to check the status of fish stocks. However, genetics cannot answer all the questions. For example, in high gene flow species the genetic approach could have not enough resolution to identify stock limits, while the use of parasites as biological tags could provide insights into stock structure. Even better, the so-called holistic approach, applying simultaneously a wide range of complementary techniques, is the only one considered able to provide a reliable and complete picture of fish stocks and to address a sustainable exploitation of marine resources. The work will present some examples from multidisciplinary studies concerning commercially relevant species with different biological features: the demersal European hake (Merluccius merluccius), the small pelagic horse mackerel (Trachurus trachurus) and the large pelagic swordfish (Xiphias gladius). In all these case studies merging genetic, parasitological and environmental data helped to reveal the real patterns of stocks structure.