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

Tic Reduction Following Heat-Induced Dehydration in Gilles de la Tourette Syndrome (TS)

A 24-year-old man with of Gilles de la Tourette (TS) syndrome experienced a marked remission of 2 years after heat-induced dehydration. Further investigation of the effects of heat and dehydration on TS may be useful

Mutations in the UQCC1-Interacting Protein, UQCC2, Cause Human Complex III Deficiency Associated with Perturbed Cytochrome b Protein Expression

Contains fulltext : 125692.pdf (publisher's version ) (Open Access)Mitochondrial oxidative phosphorylation (OXPHOS) is responsible for generating the majority of cellular ATP. Complex III (ubiquinol-cytochrome c oxidoreductase) is the third of five OXPHOS complexes. Complex III assembly relies on the coordinated expression of the mitochondrial and nuclear genomes, with 10 subunits encoded by nuclear DNA and one by mitochondrial DNA (mtDNA). Complex III deficiency is a debilitating and often fatal disorder that can arise from mutations in complex III subunit genes or one of three known complex III assembly factors. The molecular cause for complex III deficiency in about half of cases, however, is unknown and there are likely many complex III assembly factors yet to be identified. Here, we used Massively Parallel Sequencing to identify a homozygous splicing mutation in the gene encoding Ubiquinol-Cytochrome c Reductase Complex Assembly Factor 2 (UQCC2) in a consanguineous Lebanese patient displaying complex III deficiency, severe intrauterine growth retardation, neonatal lactic acidosis and renal tubular dysfunction. We prove causality of the mutation via lentiviral correction studies in patient fibroblasts. Sequence-profile based orthology prediction shows UQCC2 is an ortholog of the Saccharomyces cerevisiae complex III assembly factor, Cbp6p, although its sequence has diverged substantially. Co-purification studies show that UQCC2 interacts with UQCC1, the predicted ortholog of the Cbp6p binding partner, Cbp3p. Fibroblasts from the patient with UQCC2 mutations have deficiency of UQCC1, while UQCC1-depleted cells have reduced levels of UQCC2 and complex III. We show that UQCC1 binds the newly synthesized mtDNA-encoded cytochrome b subunit of complex III and that UQCC2 patient fibroblasts have specific defects in the synthesis or stability of cytochrome b. This work reveals a new cause for complex III deficiency that can assist future patient diagnosis, and provides insight into human complex III assembly by establishing that UQCC1 and UQCC2 are complex III assembly factors participating in cytochrome b biogenesis

The elephant in the room? Problematizing ‘new’ (neoliberal) biodiversity conservation

As argued recently in Forum for Development Studies, a ‘back to the barriers’ approach to biodiversity conservation is again prevalent, after some two decades of emphasis on ‘community-based’ initiatives. This involves the establishment and expansion of national parks from which people are variously excluded. In this article, however, I suggest that community-based approaches such as Community-Based Natural Resources Management (CBNRM) remain important, and in many ways simply constitute the other side of the same coin of modern conservation practice under the political and economic, and cultural, value-frame of neoliberalism. My aim is to highlight some shared conceptualisations and rationalisations regarding perceptions of ‘the environment’ and of people–environment relationships that inform both of these two broad-brush policy and practical orientations towards ‘biodiversity conservation’. The article thus draws on a Foucaultian analytics to ‘problematise’ the contemporary and globalising neoliberal episteme within which both these approaches are produced; and to open a space where orientations (towards ‘the environment’) that are ‘othered’ and thereby silenced by this frame might be articulated

Use of the Decipher genomic classifier among men with prostate cancer in the United States

Records of prostate cancer cases from participating SEER program registries, diagnosed during the period from 2010 through 2018, were linked to records of testing with the Decipher 22-gene genomic classifier (GC) prognostic test. Multivariable analysis was used to quantify the association between GC scores or risk groups and use of definitive local therapy after diagnosis in the GC biopsy tested cohort, and post-operative radiotherapy in the GC tested cohort as well as adverse pathology after prostatectomy.A total of 572,545 patients were included in the analysis, of which 8,927 patients underwent GC testing. GC biopsy tested patients were more likely to undergo active surveillance/watchful waiting (AS/WW) compared to untested patients (OR [95% CI] 2.21 [2.04 to 2.38], p < 0.001). AS/WW was highest for those with GC low risk classification (41%) as compared to those with intermediate (27%) or high (11%) GC risk (p < 0.001). Among NCCN low- and favorable-intermediate patients, higher GC risk was associated with greater use of local therapy (OR 4.79 [3.51 to 6.55], p < 0.001). Within this subset of patients who were subsequently treated with prostatectomy, high GC risk was associated with harboring adverse pathology (OR 2.94 [1.38 to 6.27], p = 0.005). Use of radiation after prostatectomy was significantly associated with higher GC risk group (OR 2.69 [1.89 - 3.84]).There is a strong association between use of the biopsy GC test and likelihood of conservative management. Higher genomic classifier scores are associated with higher rates of adverse pathology at time of surgery and greater use of post-operative radiotherapy. PATIENT SUMMARYThis study linked the use of the Decipher Genomic Classifier (GC) to a US national database of men with prostate cancer. Use of GC was associated with conservative management (ie, active surveillance). Among men who had high-risk GC scores and then had surgery, there was a three-fold higher chance of having worrisome findings in surgical specimens