Strategic vision for improving human health at The Forefront of Genomics.

Starting with the launch of the Human Genome Project three decades ago, and continuing after its completion in 2003, genomics has progressively come to have a central and catalytic role in basic and translational research. In addition, studies increasingly demonstrate how genomic information can be effectively used in clinical care. In the future, the anticipated advances in technology development, biological insights, and clinical applications (among others) will lead to more widespread integration of genomics into almost all areas of biomedical research, the adoption of genomics into mainstream medical and public-health practices, and an increasing relevance of genomics for everyday life.

Genomic medicine for undiagnosed diseases.

One of the primary goals of genomic medicine is to improve diagnosis through identification of genomic conditions, which could improve clinical management, prevent complications, and promote health. We explore how genomic medicine is being used to obtain molecular diagnoses for patients with previously undiagnosed diseases in prenatal, paediatric, and adult clinical settings. We focus on the role of clinical genomic sequencing (exome and genome) in aiding patients with conditions that are undiagnosed even after extensive clinical evaluation and testing.

Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease.

Background: Many patients remain without a diagnosis despite extensive medical evaluation. The Undiagnosed Diseases Network (UDN) was established to apply a multidisciplinary model in the evaluation of the most challenging cases and to identify the biologic characteristics of newly discovered diseases. The UDN, which is funded by the National Institutes of Health, was formed in 2014 as a network of seven clinical sites, two sequencing cores, and a coordinating center.

The Undiagnosed Diseases Network: Accelerating Discovery about Health and Disease.

Diagnosis at the edges of our knowledge calls upon clinicians to be data driven, cross-disciplinary, and collaborative in unprecedented ways. Exact disease recognition, an element of the concept of precision in medicine, requires new infrastructure that spans geography, institutional boundaries, and the divide between clinical care and research. The National Institutes of Health (NIH) Common Fund supports the Undiagnosed Diseases Network (UDN) as an exemplar of this model of precise diagnosis.

Newborn Sequencing in Genomic Medicine and Public Health.

The rapid development of genomic sequencing technologies has decreased the cost of genetic analysis to the extent that it seems plausible that genome-scale sequencing could have widespread availability in pediatric care. Genomic sequencing provides a powerful diagnostic modality for patients who manifest symptoms of monogenic disease and an opportunity to detect health conditions before their development. However, many technical, clinical, ethical, and societal challenges should be addressed before such technology is widely deployed in pediatric practice.

The NIH Undiagnosed Diseases Program and Network: Applications to modern medicine.

Introduction: The inability of some seriously and chronically ill individuals to receive a definitive diagnosis represents an unmet medical need. In 2008, the NIH Undiagnosed Diseases Program (UDP) was established to provide answers to patients with mysterious conditions that long eluded diagnosis and to advance medical knowledge. Patients admitted to the NIH UDP undergo a five-day hospitalization, facilitating highly collaborative clinical evaluations and a detailed, standardized documentation of the individual's phenotype.

Cardiovascular disease is associated with COPD severity and reduced functional status and quality of life.

Introduction: Smoking is a major risk factor for both cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD). More individuals with COPD die from CVD than respiratory causes and the risk of developing CVD appears to be independent of smoking burden. Although CVD is a common comorbid condition within COPD, the nature of its relationships to COPD affection status and severity, and functional status is not well understood.

eXclusion: toward integrating the X chromosome in genome-wide association analyses.

The X chromosome lags behind autosomal chromosomes in genome-wide association study (GWAS) findings. Indeed, the X chromosome is commonly excluded from GWAS analyses despite being assayed on all current GWAS microarray platforms. This raises the question: why are so few hits reported on the X chromosome? This commentary aims to examine this question through review of the current X chromosome results in the National Human Genome Research Institute Catalog of Published Genome-Wide Association Studies (NHGRI GWAS Catalog).

A common MUC5B promoter polymorphism and pulmonary fibrosis.

Background: The mutations that have been implicated in pulmonary fibrosis account for only a small proportion of the population risk.

Methods: Using a genomewide linkage scan, we detected linkage between idiopathic interstitial pneumonia and a 3.4-Mb region of chromosome 11p15 in 82 families.

Host-environment interactions in exposure-related diffuse lung diseases.

Diffuse lung disease (DLD), also known as interstitial lung disease (ILD), comprises a group of relatively rare but devastating lung diseases that involve varying degrees of acute and chronic inflammation, and which may present with end-stage fibroproliferation. There are currently no proven therapeutic strategies to halt progression of DLDs. Thinking about DLDs has evolved over time from hypotheses invoking inflammation as the prime mover in the etiology of disease, to the current hypothesis that interactions between a damaged and frustrated epithelium, and the response of underlying mesenchymal cells that takes place, contribute to the fibroproliferative milieu.