Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The global challenges and opportunities in the practice of rheumatology: white paper by the World Forum on Rheumatic and Musculoskeletal Diseases

Rheumatic and musculoskeletal diseases (RMDs) represent a multitude of degenerative, inflammatory and auto-immune conditions affecting millions of people worldwide. Persons with these diseases may potentially experience severe chronic pain, joint damage, increasing disability and even death. With an increasingly ageing population, the prevalence and burden of RMDs are predicted to increase, placing greater demands on the global practice of rheumatology and related healthcare budgets. Effective treatment of RMDs currently faces a number of challenges in both the developed and developing world, and individual countries may face more specific local challenges. However, limited understanding of the burden of RMDs amongst public health professionals and policy-makers means that these diseases are often not considered a public health priority. The objective of this review is to increase awareness of the RMDs and to identify opportunities to address RMD challenges on both a local and global scale. On 26 September 2014, rheumatology experts from five different continents met at the World Forum on Rheumatic and Musculoskeletal Diseases (WFRMD) to discuss and identify some key challenges for the RMDs community today. The outcomes are presented in this review, focusing on access to rheumatology services, diagnostics and therapies, rheumatology education and training and on clinical trials, as well as investigator-initiated and epidemiological research. The long-term vision of the WFRMD is to increase perception of the RMDs as a major burden to society and to explore potential opportunities to improve global and local RMD care

Alterations of bone mineral density, bone microarchitecture and strength in patients with ankylosing spondylitis: a cross-sectional study using high-resolution peripheral quantitative computerized tomography and finite element analysis

Abstract Introduction Ankylosing spondylitis (AS) is an inflammatory disease associated with new bone formation and an increased risk of osteoporosis and fractures. The negative effects of AS on bone microarchitecture and strength are unclear. Thus, we conducted an observational study to analyze the effect of AS on bone microarchitecture and strength. Methods Patients with AS (n = 53) and non-AS subjects (n = 85) were recruited for the study. All subjects underwent clinical evaluation, DXA and high-resolution peripheral quantitative CT scans (HRpQCT). Results The AS patients were aged 44 ± 12 (mean ± standard deviation) years and had a median disease duration of 17 (interquartile range: 7–27) years. They were found to have lower cortical, trabecular and total vBMD at the distal radius and tibia than non-AS subjects on multivariable regression analysis. Cortical parameters such as cortical thickness and porosity, and bone strength parameters such bone stiffness and stress as estimated by finite element analysis (FEA) in AS patients were significantly worse than that of-non-AS subjects. Among patients with AS, male sex, mSASSS greater than zero and HLA-B27 negative status were associated with worse bone microarchitecture. Conclusions Patients with AS have worse bone mineral density, microarchitecture and strength when compared to non-AS subjects. More research is needed to understand the mechanisms underlying bone pathology in AS and to assess the effect of treatments such as TNF inhibitors on bone quality and fracture risk