Genetics of Amyotrophic Lateral Sclerosis
AbstractPurpose of ReviewAmyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD) spectrum disorder is a rare fatal disease with strong genetic influences. The implementation of short-read sequencing methodologies in increasingly large patient cohorts has rapidly expanded our knowledge of the complex genetic architecture of the disease. We aim to convey the broad history of ALS gene discovery as context for a focused review of 11 ALS gene associations reported over the last 5 years. We also summarize the current level of genetic evidence for all previously reported genes.Recent FindingsThe history of ALS gene ...
Source: Current Genetic Medicine Reports - November 7, 2020 Category: Genetics & Stem Cells Source Type: research
Somatic Testing and Germline Genetic Status: Implications for Cancer Treatment Decisions and Genetic Counseling
AbstractPurpose of ReviewWe review recent precision oncology literature pertaining to the implications of germline and somatic genetic information in cancer treatment. The goal of this work is to provide a practical resource for oncology practitioners and genetic providers and discuss practice considerations for those on the frontline of precision oncology.Recent FindingsUnderstanding germline and somatic tumor alterations, patients can be matched to targeted therapy options attacking the specific genetic makeup of that tumor. This information informs treatment decisions about which therapies the cancer is likely to respon...
Source: Current Genetic Medicine Reports - August 12, 2020 Category: Genetics & Stem Cells Source Type: research
Exploring Beyond the DNA Sequence: A Review of Epigenomic Studies of DNA and Histone Modifications in Dementia
AbstractPurpose of ReviewAlthough genome-scale studies have identified many genetic variants associated with dementia, these do not account for all of disease incidence and so recently attention has turned to studying mechanisms of genome regulation. Epigenetic processes such as modifications to the DNA and histones alter transcriptional activity and have been hypothesized to be involved in the etiology of dementia. Here, we review the growing body of literature on dementia epigenomics, with a focus on novel discoveries, current limitations, and future directions for the field.Recent FindingsIt is through advances in genom...
Source: Current Genetic Medicine Reports - August 2, 2020 Category: Genetics & Stem Cells Source Type: research
Fertility Preservation for Genetic Indication
AbstractPurpose of ReviewThe goal of this paper is to review the current literature on fertility preservation for genetic indications and consider possible best practices for the various diagnoses.Recent FindingsThere are numerous original research articles and professional organization opinions available to inform discussions regarding fertility preservation with patients who may have compromised future fertility potential for genetic reasons.SummaryFertility preservation should be offered to any patient desiring future fertility but may be considering gonadotoxic treatment, gonadectomy, or be at risk for declining fertil...
Source: Current Genetic Medicine Reports - July 26, 2020 Category: Genetics & Stem Cells Source Type: research
When the Path to Parenthood Does Not Go as Planned: Genetic Counseling for Infertility and Miscarriage
AbstractPurpose of ReviewThe understanding of genetic contributions to miscarriage and infertility have benefited from advancements in genetic technologies, such as chromosomal microarray and next generation sequencing. Even with these modern tools, there continue to be disparities in management and counseling. This review explores recent genetic advances in reproductive health and provides evidence that genetic counseling by a genetic counselor empowers individuals to make appropriate reproductive decisions based upon their experience and values.Recent FindingsThe standard of care for products of conception testing is now...
Source: Current Genetic Medicine Reports - July 15, 2020 Category: Genetics & Stem Cells Source Type: research
Advances in Hereditary Colorectal Cancer: Opportunities and Challenges for Clinical Translation
AbstractPurpose of ReviewOver the last decade, tremendous progress has been made in our understanding, clinical evaluation, and management of hereditary colorectal cancer (CRC). This review provides an overview of recent developments and highlights opportunities and future challenges for clinical translation.Recent FindingsNovel genes have been identified associated with predisposition to CRC and polyposis including,POLE,POLD1,NTHL1,MSH3, andRNF43. Genetic testing has transitioned from phenotype-specific single-gene testing to multigene panels, and universal screening programmes for Lynch syndrome (LS) have been widely imp...
Source: Current Genetic Medicine Reports - April 2, 2020 Category: Genetics & Stem Cells Source Type: research
Genetic Testing for Cancer Predisposition Syndromes in Adolescents and Young Adults (AYAs)
AbstractPurpose of ReviewAdolescents and young adults (AYAs) represent a unique patient cohort, straddling the realms of paediatric and adult medicine. AYA cancers may include traditionally “paediatric” cancers occurring at older than expected ages, or conversely, adult-onset cancers occurring at unusually young ages. Cancer incidence in AYAs (aged 15–39) is increasing, and disappointingly, survival data are worse than those in paediatric or older adult settings. Early recognitio n of underlying cancer predisposition syndromes (CPS) in AYAs may facilitate individualised therapies, initiation of tumour surveillance st...
Source: Current Genetic Medicine Reports - March 23, 2020 Category: Genetics & Stem Cells Source Type: research
An Update on the Role of Common Genetic Variation Underlying Substance Use Disorders
AbstractPurpose of the ReviewSample size increases have resulted in novel and replicable loci for substance use disorders (SUDs). We summarize some of the latest insights into SUD genetics and discuss next steps for the field.Recent FindingsGenome-wide association studies have substantiated the role of previously known variants (e.g., rs1229984 inADH1B for alcohol) and identified several novel loci for alcohol, tobacco, cannabis, opioid, and cocaine use disorders. SUDs are genetically correlated with psychiatric outcomes, while liability to substance use is inconsistently associated with these outcomes and more closely ass...
Source: Current Genetic Medicine Reports - March 16, 2020 Category: Genetics & Stem Cells Source Type: research
Ethical Issues in Genetic Testing for Inherited Cancer Predisposition Syndromes: the Potentially Conflicting Interests of Patients and Their Relatives
AbstractPurpose of ReviewThis review uses clinical cases to highlight some of the ethical dilemmas currently faced by oncologists, geneticists and others who request genetic testing for inherited cancer disorders.Recent FindingsRecent ethical guidance supports clinicians in testing patients when other family members decline similar testing, even when such testing will reveal those family members ’ genetic status. And increasingly there is acknowledgement that when a patient declines to share genetic results with family members, cliniciansmay have an ethical duty to breach patient confidentiality in order to inform at-ris...
Source: Current Genetic Medicine Reports - March 16, 2020 Category: Genetics & Stem Cells Source Type: research
Recent Advances in Genetic Studies of Alcohol Use Disorders
AbstractPurpose of ReviewAlcohol use disorder (AUD) is a complex genetic disorder with very high heritability. Not only does this polygenic disorder result in increased morbidity and mortality, but it is also a substantial social and economic burden on families and the nation. For the past three decades, several genetic studies were conducted to identify genes and pathways associated with AUD. This review aims to summarize past efforts and recent advances in genetic association studies of AUD and related traits.Recent FindingsInitial genetic association studies achieved limited success and suffered from low power due to sm...
Source: Current Genetic Medicine Reports - March 16, 2020 Category: Genetics & Stem Cells Source Type: research
Alzheimer ’s Disease Genetics: Review of Novel Loci Associated with Disease
AbstractPurpose of the ReviewThe amyloid cascade hypothesis has shaped the Alzheimer ’s disease (AD) research field for the last 30 years. Originally hinged on mutations in theAPP pathway, its linearity has become limited to explain all the disease subtypes and features. The understanding of the disease has evolved significantly, now being viewed as a polygenic disease, with more and more risk genes uncovered by several approaches, namely, by genome-wide association studies. Here we reviewed the literature for the latest loci reported to be associated with Alzheimer ’s disease using genome-wide association studies and...
Source: Current Genetic Medicine Reports - February 3, 2020 Category: Genetics & Stem Cells Source Type: research
Network Analysis for Complex Neurodegenerative Diseases
AbstractPurpose of ReviewBiomedicine is witnessing a paradigm shift in the way complex disorders are investigated. In particular, the need for big data interpretation has led to the development of pipelines that require the cooperation of different fields of expertise, including medicine, functional biology, informatics, mathematics and systems biology. This review sits at the crossroad of different disciplines and surveys the recent developments in the use of graph theory (in the form of network analysis) to interpret large and different datasets in the context of complex neurodegenerative diseases. It aims at a professio...
Source: Current Genetic Medicine Reports - January 16, 2020 Category: Genetics & Stem Cells Source Type: research
Application of Genomics to Clinical Practice in Haematological Malignancy
AbstractPurpose of ReviewThe usual abundance of fresh cells and high-quality DNA derived from bone marrow aspirate and peripheral blood mean haematological malignancies are at the forefront of the application of genomics to malignancy. This review evaluates where genomics is routinely used in clinical care and where opportunities for further application exist.Recent FindingsThe 2016 revision of the WHO classification of tumours of haematopoietic and lymphoid tissues increased the number of disease entities defined by, or whose diagnosis was strongly supported by, a specific genetic change. Increasingly combinations of muta...
Source: Current Genetic Medicine Reports - December 1, 2019 Category: Genetics & Stem Cells Source Type: research
Opportunities for Artificial Intelligence in Advancing Precision Medicine
AbstractPurpose of ReviewWe critically evaluate the future potential of machine learning (ML), deep learning (DL), and artificial intelligence (AI) in precision medicine. The goal of this work is to show progress in ML in digital health, to exemplify future needs and trends, and to identify any essential prerequisites of AI and ML for precision health.Recent FindingsHigh-throughput technologies are delivering growing volumes of biomedical data, such as large-scale genome-wide sequencing assays; libraries of medical images; or drug perturbation screens of healthy, developing, and diseased tissue. Multi-omics data in biomedi...
Source: Current Genetic Medicine Reports - November 30, 2019 Category: Genetics & Stem Cells Source Type: research
von Hippel-Lindau Disease: an Update
AbstractPurpose of ReviewIn this review, we discuss the key molecular and clinical developments in VHL disease that have the potential to impact on the natural history of the disease and improve patient outcomes.Recent FindingsIdentifiable mutations inVHL underlie most cases of VHL and define clear genotype-phenotype correlations. Detailed clinical and molecular characterisation has allowed the implementation of lifelong screening programmes that have improved clinical outcomes. Functional characterisation of the VHL protein complex has revealed its role in oxygen sensing and the mechanisms of tumourigenesis that are now b...
Source: Current Genetic Medicine Reports - November 27, 2019 Category: Genetics & Stem Cells Source Type: research
