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

Within-subject Consistency of Paired Associative Stimulation as Assessed by Linear Mixed Models

Paired associative stimulation (PAS) is a frequently used TMS paradigm that induces long-term potentiation in the human cortex. However, little is known about the within-subject consistency of PAS-induced effects. We determined PAS-induced effects and their consistency in healthy volunteers between two PAS sessions. Additionally, we assessed the benefit of applying linear mixed models (LMMs) to PAS data. Thirty-eight healthy volunteers underwent two identical PAS sessions with a gt;1 week interval. During each session, motor evoked potentials (MEPs) were assessed once before PAS induction and 3 times after at 30 min intervals. We did not detect any significant potentiation of MEP size after PAS induction. However, MEP size during PAS induction showed significant potentiation over time in both sessions (LR(1)=13.36, plt;0.001). Nevertheless, there was poor within-subject consistency of PAS-induced effects both during (ICC=0.15) and after induction (ICC=0.04-0.09). Additionally, statistical model selection procedures demonstrate that a LMM with an unstructured covariance matrix better estimated PAS-induced effects than one with a conventional compound symmetry matrix (LR(34)=214.73, plt;0.001). While our results are supportive of a high intra-individual variability of PAS-induced effects, the generalizability of our results is unclear, as we were only partially successful in replicating results from previous PAS studies typically showing potentiation of MEPs during and after PAS induction. We do, however, demonstrate that linear mixed models can improve the reliability of PAS-induced effects estimation

Nonalcoholic Fatty Liver Disease in The Rotterdam Study: About Muscle Mass, Sarcopenia, Fat Mass, and Fat Distribution.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide. Obesity is a major risk factor for NAFLD and recently, low skeletal muscle mass emerged as additional risk factor for NAFLD. However, the different contributions of body mass index (BMI) to the risk of NAFLD are not yet well-known. We therefore studied body composition and muscle function with NAFLD in an elderly population-based study. Participants of European descent underwent dual-energy X-ray absorptiometry (DXA) and hepatic ultrasonography. NAFLD was defined as liver steatosis in absence of secondary causes for steatosis. Skeletal muscle index (SMI) was defined as appendicular lean mass/height and (pre)sarcopenia was defined using the European Working Group on Sarcopenia in Older People (EWGSOP) consensus guidelines. All analyses were stratified by sex and BMI (cut point: 25 kg/m ) and adjusted for age, weight, height, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides, and android-fat-to-gynoid-fat ratio (AGR). We included 4609 participants, of whom 1623 had NAFLD (n = 161 normal-weight and n = 1462 overweight). Presarcopenia and sarcopenia prevalence was low (5.9% and 4.5%, respectively) and both were not associated with NAFLD. SMI was associated with less NAFLD in normal-weight women (OR, 0.48; 95% CI, 0.29 to 0.80). A similar association for SMI and NAFLD was seen in normal-weight men, but significance dissipated after adjustment for AGR (OR, 0.63; 95% CI, 0.39 to 1.02). Generally, fat mass was a better predictor for NAFLD than lean mass. In particular, android fat mass was associated with all NAFLD subgroups (OR from 1.77 in overweight men to 8.34 in normal-weight women, p = 0.001), whereas substitution of gynoid fat mass for other body components had a significant protective association with NAFLD in every subgroup, but normal-weight men. Likewise, AGR was the best performing predictor for NAFLD prevalence (OR from 1.97 in normal-weight men to 4.81 in normal-weight women, p < 0.001). In conclusion, both high fat mass and low SMI were associated with normal-weight NAFLD. However, fat distribution (as assessed by AGR) could best predict NAFLD prevalence