Abstract: Previous investigations have combined transcriptional and genetic analyses in human cell lines, but few have applied these techniques to human neural tissue. To gain a global molecular perspective on the role of the human genome in cortical development, function and ageing, we explore the temporal dynamics and genetic control of transcription in human prefrontal cortex in an extensive series of post-mortem brains from fetal development through ageing. We discover a wave of gene expression changes occurring during fetal development which are reversed in early postnatal life. One half-century later in life, this pattern of reversals is mirrored in ageing and in neurodegeneration. Although we identify thousands of robust associations of individual genetic polymorphisms with gene expression, we also demonstrate that there is no association between the total extent of genetic differences between subjects and the global similarity of their transcriptional profiles. Hence, the human genome produces a consistent molecular architecture in the prefrontal cortex, despite millions of genetic differences across individuals and races. To enable further discovery, this entire data set is freely available (from Gene Expression Omnibus: accession GSE30272; and dbGaP: accession phs000417.v1.p1) and can also be interrogated via a biologist-friendly stand-alone application (http://www.libd.org/braincloud).

Abstract: Conventional experimental methods of studying the human genome are limited by the inability to independently study the combination of alleles, or haplotype, on each of the homologous copies of the chromosomes. We developed a microfluidic device capable of separating and amplifying homologous copies of each chromosome from a single human metaphase cell. Single-nucleotide polymorphism (SNP) array analysis of amplified DNA enabled us to achieve completely deterministic, whole-genome, personal haplotypes of four individuals, including a HapMap trio with European ancestry (CEU) and an unrelated European individual. The phases of alleles were determined at ∼99.8% accuracy for up to ∼96% of all assayed SNPs. We demonstrate several practical applications, including direct observation of recombination events in a family trio, deterministic phasing of deletions in individuals and direct measurement of the human leukocyte antigen haplotypes of an individual. Our approach has potential applications in personal genomics, single-cell genomics and statistical genetics.

Abstract: 632 The 9th World Congress on Genetics Applied to Livestock Production was held in Leipzig (Germany) from August 1 to August 6, 2010. There were 1385 par ticipants from 60 countries. Unfortunately, only one Russian researcher took part in the congress. Tribute should be paid to the perfect organization of such a representative forum of researchers from all over the world, which is held every four years. The main sec tions consisted of lectures and poster presentations on (1) Species breeding; (2) Genetics of trait complexes; (3) Methods and tools; (4) Genetic improvement pro grams; and (5) Special topics.

Abstract: Establishing a diagnosis in patients with a suspected mitochondrial disorder is often a challenge. Both knowledge of the clinical spectrum of mitochondrial disorders and the number of identified disease-causing molecular genetic defects are continuously expanding. The diagnostic examination of patients requires a multi-disciplinary clinical and laboratory evaluation in which the biochemical examination of the mitochondrial functional state often plays a central role. In most cases, a muscle biopsy provides the best opportunity to examine mitochondrial function. In addition to activity measurements of individual oxidative phosphorylation enzymes, analysis of mitochondrial respiration, substrate oxidation, and ATP production rates is performed to obtain a detailed picture of the mitochondrial energy-generating system. On the basis of the compilation of clinical, biochemical, and other laboratory test results, candidate genes are selected for molecular genetic testing. In patients in whom an unknown genetic variant is identified, a compatible biochemical phenotype is often required to firmly establish the diagnosis. In addition to the current role of the biochemical analysis in the diagnostic examination of patients with a suspected mitochondria disorder, this report gives a future perspective on the biochemical diagnosis in view of both the expanding genotypes of mitochondrial disorders and the possibilities for high throughput molecular genetic diagnosis.

Abstract: Part 1: Basic Principles: 1. Medical Genetics in Perspective 2. Nucleic Acid Structure and Function 3. DNA Analysis 4. Chromosomes 5. Gametogenesis 6. Chromosome Aberrations 7. Autosomal Inheritance 8. Sex-Linked Inheritance 9. Genomics 10. Non-Mendelain Inheritance 11. Medical Genetics in Populations Part 2: Clinical Applications: 12. Genetic Assessment and Counselling 13. Chromosomal Disorders 14. Single Gene Disorders 15. Immunogenetics 16. Genetics of Common Diseases 17. Cancer Genetics 18. Congenital Malformations 19. Prenatal Diagnosis 20. Population Screening 21. Prevention and Treatment Answers to Figure Questions Further Reading Appendices: 1. Odds and Probabilities 2. Applications of Bayes' Theorem 3. Calculation of the Coefficients of Relationship and Inbreeding 4. Population Genetics of Single Gene Disorders Glossary Index

Abstract: Substantial progress has been made in human genetics and genomics research over the past ten years since the publication of the draft sequence of the human genome in 2001. Findings emanating directly from the Human Genome Project, together with those from follow-on studies, have had an enormous impact on our understanding of the architecture and function of the human genome. Major developments have been made in cataloguing genetic variation, the International HapMap Project, and with respect to advances in genotyping technologies. These developments are vital for the emergence of genome-wide association studies in the investigation of complex diseases and traits. In parallel, the advent of high-throughput sequencing technologies has ushered in the 'personal genome sequencing' era for both normal and cancer genomes, and made possible large-scale genome sequencing studies such as the 1000 Genomes Project and the International Cancer Genome Consortium. The high-throughput sequencing and sequence-capture technologies are also providing new opportunities to study Mendelian disorders through exome sequencing and whole-genome sequencing. This paper reviews these major developments in human genetics and genomics over the past decade.

Abstract: A significant current challenge in human genetics is the identification of interacting genetic loci mediating complex polygenic disorders. One of the best characterized polygenic diseases is Down syndrome (DS), which results from an extra copy of part or all of chromosome 21. A short interval near the distal tip of chromosome 21 contributes to congenital heart defects (CHD), and a variety of indirect genetic evidence suggests that multiple candidate genes in this region may contribute to this phenotype. We devised a tiered genetic approach to identify interacting CHD candidate genes. We first used the well vetted Drosophila heart as an assay to identify interacting CHD candidate genes by expressing them alone and in all possible pairwise combinations and testing for effects on rhythmicity or heart failure following stress. This comprehensive analysis identified DSCAM and COL6A2 as the most strongly interacting pair of genes. We then over-expressed these two genes alone or in combination in the mouse heart. While over-expression of either gene alone did not affect viability and had little or no effect on heart physiology or morphology, co-expression of the two genes resulted in ≈50% mortality and severe physiological and morphological defects, including atrial septal defects and cardiac hypertrophy. Cooperative interactions between DSCAM and COL6A2 were also observed in the H9C2 cardiac cell line and transcriptional analysis of this interaction points to genes involved in adhesion and cardiac hypertrophy. Our success in defining a cooperative interaction between DSCAM and COL6A2 suggests that the multi-tiered genetic approach we have taken involving human mapping data, comprehensive combinatorial screening in Drosophila, and validation in vivo in mice and in mammalian cells lines should be applicable to identifying specific loci mediating a broad variety of other polygenic disorders.

Abstract: Ageing in humans is typified by the decline of physiological functions in various organs and tissues leading to an increased probability of death. Some individuals delay, escape or survive much of this age-related decline and live past age 100. Studies comparing centenarians to average-aged individuals have found polymorphisms in genes that are associated with long life, including APOE and FOXOA3, which have been replicated many times. However, the associations found in humans account for small percentages of the variance in lifespan and many other gene associations have not been replicated in additional populations. Therefore, ageing is probably a highly polygenic trait. In humans, it is important to also consider differences in age-related decline that occur within and among tissues. Longitudinal data of age-related traits can be used in association studies to test for polymorphisms that predict how an individual will change over time. Transcriptional and genetic association studies of different tissues have revealed common and unique pathways involved in human ageing. Genomic convergence is a method that combines multiple types of functional genomic information such as transcriptional profiling, expression quantitative trait mapping and gene association. The genomic convergence approach has been used to implicate the gene MMP20 in human kidney ageing. New human genetics technologies are continually in development and may lead to additional breakthroughs in human ageing in the near future.

Abstract: The identification of genes contributing to Parkinson's disease (PD) has allowed for an improved understanding of the underlying pathogenesis of the disorder. The authors review the rapidly growing field of PD genetics, with a focus on the clinical, genetic, and pathophysiologic features of well-validated monogenic forms of PD caused by mutations in the SNCA, LRRK2, PARKIN, PINK1, DJ-1, and ATP13A2 genes. In addition, they discuss mutations in the GBA gene, which increase susceptibility for PD. The authors also evaluate the implications of genome-wide association studies and stem cell-derived disease models and give recommendations for genetic testing.

Abstract: Background: Multiple sclerosis (MS) is the most common cause of chronic neurologic disability beginning in early to middle adult life. Results from recent genome-wide association studies (GWAS) have substantially lengthened the list of disease loci and provide convincing evidence supporting a multifactorial and polygenic model of inheritance. Nevertheless, the knowledge of MS genetics remains incomplete, with many risk alleles still to be revealed. Methods: We used a discovery GWAS dataset (8,844 samples, 2,124 cases and 6,720 controls) and a multi-step logistic regression protocol to identify novel genetic associations. The emerging genetic profile included 350 independent markers and was used to calculate and estimate the cumulative genetic risk in an independent validation dataset (3,606 samples). Analysis of covariance (ANCOVA) was implemented to compare clinical characteristics of individuals with various degrees of genetic risk. Gene ontology and pathway enrichment analysis was done using the DAVID functional annotation tool, the GO Tree Machine, and the Pathway-Express profiling tool. Results: In the discovery dataset, the median cumulative genetic risk (P-Hat) was 0.903 and 0.007 in the case and control groups, respectively, together with 79.9% classification sensitivity and 95.8% specificity. The identified profile shows a significant enrichment of genes involved in the immune response, cell adhesion, cell communication/ signaling, nervous system development, and neuronal signaling, including ionotropic glutamate receptors, which have been implicated in the pathological mechanism driving neurodegeneration. In the validation dataset, the median cumulative genetic risk was 0.59 and 0.32 in the case and control groups, respectively, with classification sensitivity 62.3% and specificity 75.9%. No differences in disease progression or T2-lesion volumes were observed among four levels of predicted genetic risk groups (high, medium, low, misclassified). On the other hand, a significant difference (F = 2.75, P = 0.04) was detected for age of disease onset between the affected misclassified as controls (mean = 36 years) and the other three groups (high, 33.5 years; medium, 33.4 years; low, 33.1 years). Conclusions: The results are consistent with the polygenic model of inheritance. The cumulative genetic risk established using currently available genome-wide association data provides important insights into disease heterogeneity and completeness of current knowledge in MS genetics.

Abstract: Update to: European Journal of Human Genetics (2014), doi:10.1038/ejhg.2014.170; published online 3 September 2014

Abstract: In recent years, the attention of the genomics and genetics research community has shifted toward understanding the basis of common disorders. The spectacular growth of genome-wide association studies has shed new light on the variants influencing risk factors. Understanding pathogenesis and etiology, and finding new ways to prevent and treat those diseases are major challenges. In the era of genomics, a promise of personalized prevention and drug treatment is presented, which many people meet with enthusiasm but which others call into question. The Public and Professional Policy Committee (PPPC) of the European Society of Human Genetics (ESHG), EuroGentest and the Institute for Prospective Technological Studies (IPTS) convened to discuss the relevance and possibilities of genetic testing for common disorders. Currently (in 2010), the genetics research community is skeptical about the possibilities of genetic susceptibility testing and screening contributing significantly to the improvement of the quality of health care. Meanwhile, some applications of very limited clinical utility have become available directly to consumers. Recently, the PPPC published critical recommendations on policy concerning DTC genetic testing (EJHG, 25 August 2010). When considering the potential of new genomic developments for a public health perspective, this Background Document takes the spectrum ranging from monogenic disorders on the one hand to common complex disorders on the other hand into account. It is argued that associations between genetic variants and disease risks of clinical relevance have been established, for instance for hereditary breast and ovarian cancer, colon cancer, diabetes mellitus (MODY subtypes), thrombosis, cardiovascular disorders, celiac disease and Alzheimer's disease. Although these examples relate to the monogenic subforms of common disease, they can nevertheless be used to reflect on the possibilities and relevant obstacles in using the new genetics in public health. The deliberations, reflected in the final Background Document, have led to the below recommendations from the PPPC concerning the pitfalls and possibilities of genetic testing in common disorders. A draft of both the Background Document and Recommendations has been distributed and posted on the web during the summer of 2009 to elicit further comments. The PPPC and the Board of the ESHG approved the final version. This final text is considered to reflect the views of the European human genetics scientific and professional community.

Abstract: The field of human genetics is being reshaped by exome and genome sequencing. Several lessons are evident from observing the rapid development of this area over the past 2 years, and these may be instructive with respect to what we should expect from 'next-generation human genetics' in the next few years.

Abstract: A recent phylogenomic study has provided new evidence for two ancient whole genome duplications in plants, with potential importance for the evolution of seed and flowering plants.

Abstract: The 50th anniversary of Mary Lyon's 1961 Nature paper, proposing random inactivation in early embryonic life of one of the two X chromosomes in the cells of mammalian females, provides an opportunity to remember and celebrate the work of those involved. While the hypothesis was initially put forward by Lyon based on findings in the mouse, it was founded on earlier studies, notably the work of Susumu Ohno; it was also suggested independently by Beutler and colleagues using experimental evidence from a human X-linked disorder, glucose-6-phosphate dehydrogenase deficiency, and has proved to be of as great importance for human and medical genetics as it has for general mammalian genetics. Alongside the hypothesis itself, previous cytological studies of mouse and human chromosomes, and the observations on X-linked mutants in both species deserve recognition for their essential role in underpinning the hypothesis of random X-inactivation, while subsequent research on the X-inactivation centre and the molecular mechanisms underlying the inactivation process represent some of the most outstanding contributions to human and wider mammalian genetics over the past 50 years.

Abstract: Background Genome-wide association studies (gwas) are invaluable in revealing the common variants predisposing to complex human diseases. Yet, until now, the large volumes of data generated from such analyses have not been explored extensively enough to identify the molecular and functional framework hosting the susceptibility genes. Methodology/principal findings We investigated the relationships among five neurodegenerative and/or autoimmune complex human diseases (Parkinson's disease--Park, Alzheimer's disease--Alz, multiple sclerosis--MS, rheumatoid arthritis--RA and Type 1 diabetes--T1D) by characterising the interactomes linked to their gwas-genes. An initial study on the MS interactome indicated that several genes predisposing to the other autoimmune or neurodegenerative disorders may come into contact with it, suggesting that susceptibility to distinct diseases may converge towards common molecular and biological networks. In order to test this hypothesis, we performed pathway enrichment analyses on each disease interactome independently. Several issues related to immune function and growth factor signalling pathways appeared in all autoimmune diseases, and, surprisingly, in Alzheimer's disease. Furthermore, the paired analyses of disease interactomes revealed significant molecular and functional relatedness among autoimmune diseases, and, unexpectedly, between T1D and Alz. Conclusions/significance The systems biology approach highlighted several known pathogenic processes, indicating that changes in these functions might be driven or sustained by the framework linked to genetic susceptibility. Moreover, the comparative analyses among the five genetic interactomes revealed unexpected genetic relationships, which await further biological validation. Overall, this study outlines the potential of systems biology to uncover links between genetics and pathogenesis of complex human disorders.

Abstract: Purpose of reviewRecent genome-wide association studies (GWAS) have identified approximately 100 genomic loci that are associated with plasma lipid traits, two-thirds of which had never been previously associated with lipoprotein metabolism. Identification of the causal genes and variants, functiona

Abstract: Recent studies have investigated the contribution of copy number variants (CNVs) to disease susceptibility in a multitude of complex disorders, including systemic lupus erythematosus, Crohn's disease, and various neurodevelopmental disorders. Relatively few CNV studies, however, have been conducted on pharmacologic phenotypes even though these structural variants are likely to play an important role. We developed a genome-wide method to identify CNVs that contribute to heterogeneity in drug response, focusing on drugs that are widely used in anticancer treatment regimens. We conducted a comprehensive genome-wide study of CNVs from population-scale array-based and sequencing-based surveys by analyzing their effect on cellular sensitivity to platinating agents and topoisomerase II inhibitors. We identified extensive CNV regions associated with cellular sensitivity to functionally diverse chemotherapeutics, supporting the hypothesis that variation in copy number contributes to variation in drug response. Interestingly, although single nucleotide polymorphisms (SNPs) tag some of the CNVs associated with drug sensitivity, several of the most significant CNV-drug associations are independent of SNPs; consequently, they represent genetic variations that have not been previously interrogated by SNP studies of pharmacologic phenotypes. Our findings demonstrate that pharmacogenomic studies may greatly benefit from the study of CNVs as expression quantitative trait loci, thus contributing broadly to our understanding of the complex traits genetics of CNVs. We also extend our PACdb resource, a database that makes available to the scientific community relationships between genetic variation, gene expression, and sensitivity to various drugs in cell-based models.

Abstract: Levels of transcripts sharing microRNA response elements are co-regulated. These RNA-RNA interactions imply that combinations of microRNAs modulate cell-specific transcript networks.

Abstract: Recent developments, including next-generation sequencing (NGS), bio-ontologies and the Semantic Web, and the growing role of hospital information technology (IT) systems and electronic health records, amass ever-increasing amounts of data before human genetics scientists and clinicians. However, they have ever-improving tools to analyze those data for research and clinical care. Correspondingly, the field of bioinformatics is turning to research questions in the field of human genetics, and the field of human genetics is making greater use of bioinformatic algorithms and tools. The choice of "Bioinformatics and Human Genetics" as the topic of this special issue of Human Mutation reflects this new importance of bioinformatics and medical informatics in human genetics. Experts from among the attendees of the Paris 2010 Human Variome Project symposium provide a survey of some of the "hot" computational topics over the next decade. These experts identify the promise-what human geneticists who are not themselves bioinformaticians stand to gain-as well as the challenges and unmet needs that are likely to represent fruitful areas of research.

Abstract: Purpose of review Recent advancements in genotyping technology have contributed to an accelerated dissemination of information on sequence variation associated with hepatobiliary diseases and/or quantitative traits. Recent findings Since the first genome-wide association study (GWAS) on genetic gallstone risk in 2007, a total of more than 25 GWAS related to the field have been reported. The identification of the IL-28B genotype as a critical host factor of natural and treatment-related outcomes in hepatitis C virus infection opens the avenue of personalized medicine and individual risk assessment by genetic information. By contrast, the second recent top-hit variant adiponutrin (PNPLA3) associated with liver fat content and fibrosis progression illustrates the potential of GWAS to identify novel pathobiological pathways. Another emerging research topic is in the designation of genetic markers for specific cirrhosis-related complications, such as spontaneous bacterial peritonitis (NOD2) and hepatic encephalopathy (glutaminase), of potential future relevance in prioritizing patients for preemptive treatment strategies. Summary In this article we critically discuss new concepts in the genetics of hepatobiliary diseases with a special focus on the advantages and limitations of the GWAS approach. An update on relevant recent GWAS and selected candidate gene study data will be given.

Abstract: Although human disease genes generally tend to be evolutionarily more ancient than non-disease genes, complex disease genes appear to be represented more frequently than Mendelian disease genes among genes of more recent evolutionary origin. It is therefore proposed that the analysis of human-specific genes might provide new insights into the genetics of complex disease. Cross-comparison with the Human Gene Mutation Database (http://www.hgmd.org) revealed a number of examples of disease-causing and disease-associated mutations in putatively human-specific genes. A sizeable proportion of these were missense polymorphisms associated with complex disease. Since both human-specific genes and genes associated with complex disease have often experienced particularly rapid rates of evolutionary change, either due to weaker purifying selection or positive selection, it is proposed that a significant number of human-specific genes may play a role in complex disease.

Abstract: Schizophrenia is a common mental disorder, affecting 0.5–1% of the population. The mode of inheritance is complex and non-Mendelian with a high heritability of ca. 65–80%. Given this complexity, until most recently it was difficult to identify disease genes. But fortunately this has changed. Due to new technologies the last few years have brought highest interest in human genetics of complex diseases. The knowledge resulting from the availability of the complete sequence of the human genome, the systematic identification of single nucleotide polymorphisms (SNPs) throughout the genome, and the development of parallel genotyping technology (microarrays) established the conditions that brought about the current successful time in our ability to probe the genome for identifying disease genes. All these studies showed up new avenues for the biology of common complex diseases and yielded a multitude of genes showing strong association with complex diseases.

Abstract: The book, Neurogenetic syndromes: Behavioral issues and their management, is edited by two experts in behavioral issues in neurodevelopmental conditions. Dr. Bruce Shapiro is a Professor of Pediatrics at the Johns Hopkins Medical School and Vice President of Training at the prestigious Kennedy Krieger Institute. Dr. Pasquale Accardo is a Professor of Pediatrics with particular interest in developmental research at Virginia Commonwealth University. As a genetic counselor who works with adult onset neurogenetic conditions, I was asked to review this book for the Journal of Genetic Counseling. While the title of this book emphasizes “Neurogenetic Syndromes,” this is not a book that addresses behavioral issues seen in neurogenetic syndromes characterized by adult onset neurodegeneration (e.g., Huntington disease or frontotemporal dementia). An alternative title such as “Behavioral Issues in Developmental Neurogenetic Syndromes” might better describe the focus of this book. It is important to consider what the authors do and do not wish to achieve in this brief 300-page book. This volume is not (nor do the Editors intend it to be) an encyclopedic reference of genetic conditions with significant developmental/behavioral features. This book does not address specific genetic counseling issues per se in that it is not focused on topics such as recurrence risks. Finally, this is not a book the Editors intended to exhaustively cover the fields of developmental pediatrics and psychology. What this book does, and does well, is bridge the gaps between genetics, developmental pediatrics, behavioral research, and basic science. The editors present 17 brief, well referenced chapters that help to illustrate critical issues at the intersection of these disciplines. The authors are primarily clinicians and they often draw on their clinical experience to supplement the published medical literature. The book is divided into three discrete sections. The first section contains eight chapters most of which focus on a single genetic neurodevelopmental condition to illustrate a larger point. For example, Prader Willi syndrome is used as a launching point for a discussion of the concept of an “endophenotype.” The chapter on Fragile X syndrome touches on the issue of common behavioral/psychiatric diagnoses (e.g., autism spectrum disorder) and their relationship to Mendelian conditions. Each chapter reviews historical features, clinical features, and genetic mechanisms with an eye towards making a specific point (e.g.,. how triplication of hundreds of genes may lead to a consistent Down syndrome behavioral phenotype). In other chapters authors describe how behaviors can be recognized, categorized (or miscategorized), and studied in a systematic fashion. This first section of the book is heavy on technical discussion and light on story-telling. Each chapter includes healthy doses of neuroanatomy, neurotransmitters, functional brain circuits, etc. The authors enrich their discussions with their own unpublished or anecdotal findings. Given the lack of published behavioral data for many of the rare Mendelian conditions, and the extensive experience of the authors, this is a valuable contribution to this book. The second section of the book shifts the focus from specific neurogenetic conditions to specific strategies for M. A. Bower Division of Genetics and Metabolism, University of Minnesota Medical Center, Fairview, Minneapolis, MN 55455, USA

Abstract: Evidence of a genetic control of pain has led to efforts to exploit genotyping information from pain patients for the development of analgesics and for the selection of pharmacological approaches to pain. Research on translating the genetic bases of familial insensitivity to pain has contributed to the discovery of crucial molecular pathways of pain and to the identification of new analgesic targets (e.g., the Na(v)1.7 sodium channel, neurotrophic tyrosine kinase receptors, nerve growth factor). Moreover, human genetic variants leading to enhanced or reduced function of specific molecular pathways are employed as substitutes for the lack of modulator molecules usable in humans, enabling nociceptive or anti-nociceptive pathways in humans to be studied before drug development. Translational approaches have also been used to verify the importance of experimentally discovered pain pathways in humans, such as GTP cyclohydrolase 1 and the potassium channel K(v)9.1. In addition to these uses of genetics as a research tool, an individualized pharmacological therapy based on the patient's genotype has been attempted. In terms of analgesics in clinical use, such an approach is at the present time only marginally available. For future analgesic targeting, for example, Na(v)1.7 or TRPA1, the genotype may be the target of a selective cure for syndromes caused by increased-function mutations in the coding genes. The consideration of human genetics in drug studies may accelerate analgesic drug development while reducing cost because the clinical success may be partly anticipated by including information of functional genetic variants that mimic the action of future analgesics. These developments show that genotyping information obtained from studies on pain patients plays a role in the clinical pharmacology of pain.

Abstract: Capan-1 is a well-characterised BRCA2-deficient human cell line isolated from a liver metastasis of a pancreatic adenocarcinoma. Here we report a genome-wide assessment of structural variations and high-depth exome characterization of single nucleotide variants and small insertion/deletions in Capan-1. To identify potential somatic and tumour-associated variations in the absence of a matched-normal cell line, we devised a novel method based on the analysis of HapMap samples. We demonstrate that Capan-1 has one of the most rearranged genomes sequenced to date. Furthermore, small insertions and deletions are detected more frequently in the context of short sequence repeats than in other genomes. We also identify a number of novel mutations that may represent genetic changes that have contributed to tumour progression. These data provide insight into the genomic effects of loss of BRCA2 function.

Abstract: “Genomic medicine” refers to the diagnosis, optimized management, and treatment of disease—as well as screening, counseling, and disease gene identification—in the context of information provided by an individual patient’s personal genome. Genomic medicine, to some extent synonymous with “personalized medicine,” has been made possible by recent advances in genome technologies. Genomic medicine represents a new approach to health care and disease management that attempts to optimize the care of a patient based upon information gleaned from his or her personal genome sequence. In this review, we describe recent progress in genomic medicine as it relates to neurological disease. Many neurological disorders either segregate as Mendelian phenotypes or occur sporadically in association with a new mutation in a single gene. Heritability also contributes to other neurological conditions that appear to exhibit more complex genetics. In addition to discussing current knowledge in this field, we offer suggestions for maximizing the utility of genomic information in clinical practice as the field of genomic medicine unfolds.

Abstract: The DNA sequencing technology developed by Frederick Sanger in the 1970s established genomics as the basis of comparative genetics. The recent invention of next-generation sequencing (NGS) platform has added a new dimension to genome research by generating ultra-fast and high-throughput sequencing data in an unprecedented manner. The advent of NGS technology also provides the opportunity to study genetic diseases where sequence variants or mutations are sought to establish a causal relationship with disease phenotypes. However, it is not a trivial task to seek genetic variants responsible for genetic diseases and even harder for complex diseases such as diabetes and cancers. In such polygenic diseases, multiple genes and alleles, which can exist in healthy individuals, come together to contribute to common disease phenotypes in a complex manner. Hence, it is desirable to have an approach that integrates omics data with both knowledge of protein structure and function and an understanding of networks/pathways, i.e. functional genomics and systems biology; in this way, genotype–phenotype relationships can be better understood. In this review, we bring this ‘bottom-up’ approach alongside the current NGS-driven genetic study of genetic variations and disease aetiology. We describe experimental and computational techniques for assessing genetic variants and their deleterious effects on protein structure and function.

Abstract: Double minute chromosomes (DMs) are small chromatin bodies consisting of gene amplification in an extrachromosomal location. Although found in an variety of human tumor cells, their presence in hematologic malignancies is rare and their role in leukemogenesis is controversial. However, they are thought to be involved in tumorigenesis and in drug resistance, representing a mechanism for upregulated oncogene expression generally associated with a poor prognosis. The presence of DMs has been associated with a rapid disease course, low response rate, and short survival. Little knowledge is, however, available on DMs in leukemias. To elucidate this issue, a web-based search for all types of articles published was initiated using MEDLINE/PubMed, the Mitelman database and other pertinent references on websites. We found that DMs have the highest frequency in adrenal carcinoma (28.6%), and lowest rate noted as 2.6% for large intestine. The large Mitelman database and other web based pertinent reports provide novel knowledge of DMs and their association in the wide field of cancers.