Genetic Variants and Related Biomarkers in Sporadic Alzheimer’s Disease
Abstract
From a neuropathological perspective, elderly patients who die with a clinical diagnosis of sporadic Alzheimer’s disease (AD) are a heterogeneous group with several different pathologies contributing to the AD phenotype. This poses a challenge when searching for low effect size susceptibility genes for AD. Further, control groups may be contaminated by significant numbers of preclinical AD patients, which also reduces the power of genetic association studies. Here, we discuss how cerebrospinal fluid and imaging biomarkers can be used to increase the chance of finding novel susceptibility genes ...
Source: Current Genetic Medicine Reports - December 24, 2014 Category: Genetics & Stem Cells Source Type: research
Recent Discoveries in the Reproductive Control of Aging
Abstract
Reproduction is an energetically expensive endeavor that has profound influences on many life history traits, including the length of life. Reduced reproduction is associated with increased longevity in many organisms. Similarly, mating has been reported to shorten the lifespan of females in multiple species. Contemporary studies in model organisms have begun to unravel the molecular complexities that govern the relationship between reproduction and longevity. Here, we discuss recent discoveries that examine the genetic mechanisms by which two contrasting reproductive events—germline loss and s...
Source: Current Genetic Medicine Reports - December 18, 2014 Category: Genetics & Stem Cells Source Type: research
Genetic and Molecular Basis for Hereditary Hemorrhagic Telangiectasia
Abstract
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder that predisposes patients to develop direct connections between arteries and veins, or arteriovenous malformations (AVMs). Although the genes responsible for the majority of HHT cases have been known for nearly 20 years, molecular and cellular mechanisms underlying pathogenesis are poorly understood, and the genetic and/or environmental factors that confer variability to age of onset and expressivity of HHT remain unknown. Herein, we review the genetics and genotype/phenotype correlations associated with HHT and summar...
Source: Current Genetic Medicine Reports - December 16, 2014 Category: Genetics & Stem Cells Source Type: research
Genetic and Molecular Aspects of Frontotemporal Lobar Degeneration
Abstract
Frontotemporal lobar degeneration (FTLD) is a neuropathologically and genetically heterogeneous group of neurodegenerative syndromes leading to dementia and primarily affecting frontal and temporal lobes. FTLD patients can develop non-cognitive symptoms in keeping with amyotrophic lateral sclerosis or parkinsonian syndromes. This wide clinical spectrum is explained to some extent with similar pathological and genetic backgrounds. FTLD shows a strong familial component, with up to 50 % of cases having a positive family history. So far, mutations in seven genes are known to cause autosomal dominan...
Source: Current Genetic Medicine Reports - December 16, 2014 Category: Genetics & Stem Cells Source Type: research
Epigenetic Developmental Disorders: CHARGE Syndrome, a Case Study
Abstract
Epigenetic events including chromatin remodeling and histone modifications have recently emerged as important contributors to a variety of neurodevelopmental disorders. This review focuses on CHARGE syndrome, a multiple anomaly condition caused by mutations in the gene encoding CHD7, an ATP-dependent chromatin remodeling protein. CHD7 exhibits pleiotropic effects during embryonic development, consistent with highly variable clinical features in CHARGE syndrome. In this review, a historical description of CHARGE is provided, followed by establishment of diagnostic criteria, gene discovery, and dev...
Source: Current Genetic Medicine Reports - December 5, 2014 Category: Genetics & Stem Cells Source Type: research
The Influences of Genetic and Environmental Factors on Methylome-Wide Association Studies for Human Diseases
Abstract
DNA methylation (DNAm) is an essential epigenetic mechanism for normal development, and its variation may be associated with diseases. High-throughput technology allows robust measurement of DNA methylome in population studies. Methylome-wide association studies (MWAS) scan the DNA methylome to detect new epigenetic loci affecting disease susceptibility. MWAS is an emerging approach to unraveling the mechanism linking genetics, environment, and human diseases. Here I review the recent studies of genetic determinants and environmental modifiers of DNAm, and the concept for partitioning genetic an...
Source: Current Genetic Medicine Reports - September 25, 2014 Category: Genetics & Stem Cells Source Type: research
Understanding the Paradigm Challenges Posed by Multiplex Panel Testing for Cancer Susceptibility
Abstract
Massively parallel (“next generation”) sequencing (MPS) is a technology that has revolutionized genetics. In clinical cancer genetics, MPS affords the opportunity to concurrently analyze the sequence of an arbitrary number of genes that may be related to a clinical presentation, such as breast cancer. This multiplex panel testing may identify germ line pathogenic variants in genes that would not have been tested on phenotypic grounds. While this type of testing may be beneficial in specific circumstances, broad application introduces challenges that cannot easily be addressed by conventional ...
Source: Current Genetic Medicine Reports - September 25, 2014 Category: Genetics & Stem Cells Source Type: research
Management Strategies for Ethics in International Research
Abstract
PERSPECTIVE is a large-scale, international research project that aims to develop a risk stratification approach for breast cancer screening. This project involving many researchers as well as samples and data from 30 different countries creates novel ethical challenges. We discuss some specific issues that have arisen in the context of the PERSPECTIVE project as well as the innovative strategies conceived to address them. Even in the absence of an overarching international organization for the ethics review of multisite research projects, an adapted, flexible ethical framework, together with cus...
Source: Current Genetic Medicine Reports - September 19, 2014 Category: Genetics & Stem Cells Source Type: research
After Myriad: Genetic Testing in the Wake of Recent Supreme Court Decisions about Gene Patents
Abstract
Genetic testing is becoming more common and more powerful by the day. The costs of the underlying DNA sequencing technology are plummeting, making it likely that tests based on it will become even more pervasive. The use of tests to determine DNA sequence to help make clinical decisions is here to stay. DNA sequencing is also finding new uses in forensics, determination of ancestry, understanding the history and genetic lineages of human populations and many other applications. (Source: Current Genetic Medicine Reports)
Source: Current Genetic Medicine Reports - September 11, 2014 Category: Genetics & Stem Cells Source Type: research
Cross-Disorder Comparison of Four Neuropsychiatric CNV Loci
Abstract
Copy number variants (CNVs) have been identified as a major risk factor in neuropsychiatric disorders. In this review, we describe the phenotypes and syndromic features associated with CNVs at four of the best-characterized risk loci for these disorders: 15q11.2-13.1, 22q11.2, 16p11.2, and 7q11.23. By considering the reported prevalence of these CNVs in autism, intellectual disability, schizophrenia, and controls, we demonstrate a pattern of asymmetric shared risk in which CNVs increase the risk of multiple disorders but to differing degrees. This asymmetric risk sharing is incompatible with a ...
Source: Current Genetic Medicine Reports - September 1, 2014 Category: Genetics & Stem Cells Source Type: research
Pharmacogenomics for Precision Medicine in the Era of Collaborative Co-creation and Crowdsourcing
Abstract
The whole gamut of new technologies in the past decade has revolutionized DNA sequencing, making it cheaper, efficient, and scalable. The consequent big-data in genomics have posed new challenges and opportunities. The transformation of internet as a fabric that intertwines multiple technological and social layers and the rise of platforms that can organize and integrate massively parallel human activities have transformed the workplaces in many industries and offers a new opportunity in the area of genomics. In this short review, we discuss the state-of-the art of crowdsourcing in genom...
Source: Current Genetic Medicine Reports - September 1, 2014 Category: Genetics & Stem Cells Source Type: research
Advances in Genetic Discovery and Implications for Counseling of Patients and Families with Autism Spectrum Disorders
Abstract
The prevalence of autism spectrum disorders (ASD) continues to increase. Genetic factors play an important role in the etiology of ASD, although specific genetic causes are identified in only a minority of cases. Recent advances have accelerated the discovery of genes implicated in ASD through convergent genomic analysis of genome-wide association studies, chromosomal microarray, exome sequencing, genome sequencing, and gene networks. Hundreds of candidate genes for ASD have been reported, yet only a handful have proven causative. Symptoms are complex and highly variable, and most cases are lik...
Source: Current Genetic Medicine Reports - September 1, 2014 Category: Genetics & Stem Cells Source Type: research
The Rapidly Emerging Role for Whole Exome Sequencing in Clinical Genetics
Abstract
Sequencing of the exome, the protein-coding region of the human genome, has quickly grown into a new approach for clinical diagnosis of disease. Enabled by next-generation sequencing technologies, clinical exomes accompanied by clinical interpretation of the genome variants are used today to guide health care providers in understanding and diagnosing their patient’s disease. Continuing improvement in both sequencing technology and exome approaches, as well as interpretation of the variation identified, will be required to fully realize the power of this new science. This review provides a gli...
Source: Current Genetic Medicine Reports - September 1, 2014 Category: Genetics & Stem Cells Source Type: research
The Genetics of Common Epilepsy Disorders: Lessons Learned from the Channelopathy Era
Abstract
Idiopathic epilepsies are thought to be almost entirely the result of genetic determinants, most of which remain undiscovered. It was once widely accepted that mutations that change the amino acid sequence of ion channel proteins were the major cause of these epilepsies, making epilepsy in general a “channelopathy.” Since then, more comprehensive analysis of ion channel-encoding genes has largely rejected this hypothesis for common forms of epilepsy. Here, we discuss some of the assumptions that led to the channelopathy hypothesis and propose ways to avoid similar mistakes going forward. We...
Source: Current Genetic Medicine Reports - September 1, 2014 Category: Genetics & Stem Cells Source Type: research
Copy Number Variation in Congenital Heart Defects
Abstract
Congenital heart defects (CHDs) are the most common birth defect and a major contributor to mortality, morbidity, and healthcare costs throughout the world. Although improvements in surgical advances and cardiac care have increased the lifespan of individuals with CHDs, the underlying etiologies of disease remain elusive and there have been no interventions that decrease disease incidence. Genetic, epigenetic, and environmental factors all influence the development of CHDs, and an improved understanding of causation is a prerequisite for prevention. Genetic causes of CHDs include both structura...
Source: Current Genetic Medicine Reports - September 1, 2014 Category: Genetics & Stem Cells Source Type: research
