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The application of genetic knowledge to benefit human health has never looked more promising. Next-generation sequencing technologies are helping to reveal the links between genomic variants and simple and complex traits; stem cells are being harnessed for use in regenerative medicine; and some gene-based therapies achieving clinical success.
The articles in this series document the many ways in which genetic knowledge is changing medical practice, by facilitating screening tests, by informing diagnoses and drug prescribing and, perhaps before long, by routinely offering personalized health-risk assessments and tailored treatments.
Polygenic risk profiling can lead to actionable outcomes for individuals at high risk of developing a subset of common adult-onset polygenic diseases. The authors review recent studies that have demonstrated the utility of polygenic risk scores for disease risk stratification and their potential impact on early disease detection, prevention, therapeutic intervention and life planning.
Recent studies show that structural variation can alter the genome architecture, leading to changes in the regulation of gene expression that cause disease. The authors review the role of genetic structural variation in disease and the pathogenic potential of changes to the 3D genome.
The emerging field of paediatric genomics has leveraged the power of next-generation sequencing technologies to improve the diagnostic rates of rare disease in children. This Review addresses key considerations for safe and effective implementation of genomics in the clinic.
Including diverse populations in genomic studies has the potential to improve the use of genomic data in the clinic. Here, members of the National Human Genome Research Institute review the benefits of increasing diversity, the challenges to overcome and key recommendations for how to achieve this goal.
Various large studies have provided unprecedented insights into the genetics of autism spectrum disorders (ASDs). This Review discusses the challenges and opportunities of translating genetic and biological insights into clinical progress for ASDs, in areas including genetic testing, ASD classification, genetic counselling, comorbidities and therapeutics.
Advances in genetics and genomics have transformed the field of organ transplantation. Here, the authors review the role of genetic dissimilarities between donor and recipient in transplant tolerance and rejection, and how the identification of genetic variants that predict adverse transplant outcomes can be used for personalized medicine.
The advent of genomic technologies is changing health care systems, with genomic data increasingly being applied to guide individual patient care. In this Essay, Rehm discusses how genomics is becoming an essential part of clinical care and the existing challenges that must be surmounted to take full advantage of personal genomic information.
The identification of mutations that underlie rare diseases has dramatically accelerated in recent years thanks to next-generation sequencing. This Review discusses strategies for further identification studies, insights into disease mechanisms and the clinical implications of the rapid progress in this field of research.
Despite the impact of genome-wide association studies (GWASs) on disease genetics, there has been scepticism about their usefulness in clinical translation. This Review highlights pertinent examples in which clinical application has been achieved or is likely and considers the wider potential for translation.
Several promising genetic approaches are being investigated for the treatment of Duchenne muscular dystrophy, including traditional gene therapy, stop codon read-through, exon skipping and increased expression of a compensatory gene. The lessons learned should also be valuable for other disorders.
The authors review current technologies for clinical genetic testing. Moves are being made towards whole-genome and whole-exome sequencing in the clinic, although other technologies will continue to be of value.
Clinical sequencing tests that focus on genes linked to specific diseases or phenotypes are increasingly widely being used. This article discusses how disease-targeting tests retain several advantages despite moves towards the clinical application of whole-genome or exome sequencing.
In addition to somatic mutations in tumours, inherited genetic variants can influence how a patient with cancer responds to drug treatment. This Review considers best practice in design and analysis for pharmacogenomic studies to identify such variants, potentially leading to personalized oncology.
Epigenetic alterations, notably in DNA hypermethylation, are emerging as consistent biomarkers for disease. Here, with a focus on cancer, the authors discuss the identification of these biomarkers and their use in disease diagnosis, prognosis and response to therapy.
The adoption of electronic health records will provide a rich resource for biomedical researchers. This Review discusses the potential for their use in informed decision making in the clinic, for a finer understanding of genotype–phenotype relationships and for selection of research cohorts, along with the current challenges for their mining and use.
Owing to the important role of microRNAs in gene regulation, profiling repertoires of expressed microRNAs can be informative in basic research and clinical settings. This Review describes the methods that are available for microRNA profiling and considerations for choosing among analytical options.
Exome sequencing is a powerful approach for accelerating the discovery of the genes underlying Mendelian disorders and, increasingly, of genes underlying complex traits. This Review describes the experimental and analytical options for applying exome sequencing and the key challenges in using this approach.
Direct-to-consumer (DTC) genetic tests allow individuals to learn about their health or that of their future offspring. Should we protect individuals from potentially misleading genetic information about themselves or should we assume that adults who seek DTC services can interpret the genetic findings even without the intervention of a health professional? We present five different perspectives on whether DTC genetic tests should be regulated and, if so, how.
This Review describes the state-of-the-art accomplishments that have been made with gene-based therapies and the major barriers that need to be overcome before these tools are more widely implemented by the medical community.
Recent clinical and preclinical studies have described exciting results using recombinant adeno-associated virus (AAV) vectors for therapeutic gene transfer in genetic disease. This Review explores the potential for using this form of therapy in the context of different tissues and diseases.
Cell-based therapy is a growing field that exploits advances in stem cell manipulation and gene transfer technologies. This Review discusses the latest developments and crucial challenges for this field, with an emphasis on haematopoietic stem cell gene therapy.
RNA interference can elicit specific gene silencing and so holds great potential for treating infectious or genetic diseases. Several small-RNA-based therapies have now reached clinical trials, but further work is still needed to improve delivery and efficacy.
There are now myriad variations on techniques to reprogramme somatic cells into pluripotent stem cells, but which options should researchers choose? This Review sets out the choices, focusing on how the desired downstream application should guide the reprogramming strategy.
Pluripotent stem cells can become any cell in the body, and yet achieving this in the laboratory is a challenge. Popular methods include directing differentiation using protein factors or small molecules, and an emerging alternative is reprogramming somatic cells directly from one fate to another.
Thanks to improved functional assays and more effective protocols for directed tissue differentiation, pluripotent stem cells are proving increasingly useful for uncovering the genetic and epigenetic basis of monogenic and complex diseases, and for investigating the functional consequences of genetic variation.
Prediction of genetic values using whole-genome markers has been successfully applied in commercial breeding. This article outlines the use of this method for predicting health-related outcomes in humans.
The use of genome-wide association (GWA) approaches to identify variants that affect drug response or reaction is increasing rapidly, with at least 12 studies appearing in 2009 alone. This article reviews these pharmacogenomics GWA studies, and the prospects for this field.
