Spring migration of Ruffs Philomachus pugnax in Fryslân: estimates of staging duration using resighting data

Seasonal bird migration involves long flights, but most time is actually spent at intermediate staging areas. The duration of stay at these sites can be evaluated with mark–recapture methods that employ day-to-day local encounters of individually marked birds. Estimates of staging duration are based on two probabilities: the immigration probability, the complement of a bird’s seniority to an area, and the emigration probability, the complement of the staying probability. Estimating total staging duration from seniority and staying probabilities requires validation for resighting data and here we compare three data categories of Ruffs Philomachus pugnax passing through The Netherlands during northward migration: (1) newly colour-ringed, (2) previously colour-ringed and (3) radio-tagged Ruffs (recorded by automated receiving stations). Between 2004 and 2008, 4363 resighting histories and 95 telemetry recording histories were collected. As sample sizes for females were low, only data for males were analysed. Possible catching effects affecting estimates of staging duration were explored. Staying probability was estimated for all data. Seniority however, could not be estimated for newly marked Ruffs; the assumption of equal ‘capture’ probability for reverse-time models applied to estimate seniority is violated for seasonal resighting histories starting with a catching event. Therefore, estimates of total staging duration were based on resightings of previously colour-marked birds only. For radio-tagged birds a minimal staging duration (time between tagging and last recording) was calculated. Modelling indicated that newly colour-ringed birds had a higher staying probability than previously colour-ringed birds, but the difference translated to a prolonged staging duration in newly ringed birds of only 0.4–0.5 d, suggesting a very small catching effect. The minimal staging duration of radio-tagged birds validated estimates of staging duration for colour-ringed birds in 2007 but not in 2005. In 2005 a low resighting probability resulted in underestimates of staging duration. We conclude that (1) estimates of staying probability can be affected by catching although effects on staging duration might be small, and that (2) low resighting probabilities can lead to underestimates in staging duration. In our study previously ringed Ruffs resighted in 2006–08 yielded reliable estimates of staging duration as data had sufficiently high resighting probabilities. Average staging durations varied between 19 d in 2008 and 23 d in 2006.

From genome-wide association studies to disease mechanisms:celiac disease as a model for autoimmune diseases

Celiac disease is characterized by a chronic inflammatory reaction in the intestine and is triggered by gluten, a constituent derived from grains which is present in the common daily diet in the Western world. Despite decades of research, the mechanisms behind celiac disease etiology are still not fully understood, although it is clear that both genetic and environmental factors are involved. To improve the understanding of the disease, the genetic component has been extensively studied by genome-wide association studies. These have uncovered a wealth of information that still needs further investigation to clarify its importance. In this review, we summarize and discuss the results of the genetic studies in celiac disease, focusing on the "non-HLA" genes. We also present novel approaches to identifying the causal variants in complex susceptibility loci and disease mechanisms

Meta-Analysis of Genome-Wide Linkage Studies in Celiac Disease.

OBJECTIVE: A meta-analysis of genome-wide linkage studies allows us to summarize the extensive information available from family-based studies, as the field moves into genome-wide association studies. METHODS: Here we apply the genome scan meta-analysis (GSMA) method, a rank-based, model-free approach, to combine results across eight independent genome-wide linkages performed on celiac disease (CD), including 554 families with over 1,500 affected individuals. We also investigate the agreement between signals we identified from this meta-analysis of linkage studies and those identified from genome-wide association analysis using a hypergeometric distribution. RESULTS: Not surprisingly, the most significant result was obtained in the HLA region. Outside the HLA region, suggestive evidence for linkage was obtained at the telomeric region of chromosome 10 (10q26.12-qter; p = 0.00366), and on chromosome 8 (8q22.2-q24.21; p = 0.00491). Testing signals of association and linkage within bins showed no significant evidence for co-localization of results. CONCLUSION: This meta-analysis allowed us to pool the results from available genome-wide linkage studies and to identify novel regions potentially harboring predisposing genetic variation contributing to CD. This study also shows that linkage and association studies may identify different types of disease-predisposing variants

Multi-ethnic studies in complex traits

The successes of genome-wide association (GWA) studies have mainly come from studies performed in populations of European descent. Since complex traits are characterized by marked genetic heterogeneity, the findings so far may provide an incomplete picture of the genetic architecture of complex traits. However, the recent GWA studies performed on East Asian populations now allow us to globally assess the heterogeneity of association signals between populations of European ancestry and East Asians, and the possible obstacles for multi-ethnic GWA studies. We focused on four different traits that represent a broad range of complex phenotypes, which have been studied in both Europeans and East Asians: type 2 diabetes, systemic lupus erythematosus, ulcerative colitis and height. For each trait, we observed that most of the risk loci identified in East Asians were shared with Europeans. However, we also observed that a significant part of the association signals at these shared loci seems to be independent between populations. This suggests that disease aetiology is common between populations, but that risk variants are often population specific. These variants could be truly population specific and result from natural selection, genetic drift and recent mutations, or they could be spurious, caused by the limitations of the method of analysis employed in the GWA studies. We therefore propose a three-stage framework for multi-ethnic GWA analyses, starting with the commonly used single-nucleotide polymorphism-based analysis, and followed by a gene-based approach and a pathway-based analysis, which will take into account the heterogeneity of association between populations at different levels

Type 2 Diabetes Mellitus: New Genetic Insights will Lead to New Therapeutics

Type 2 diabetes is a disorder of dysregulated glucose homeostasis. Normal glucose homeostasis is a complex process involving several interacting mechanisms, such as insulin secretion, insulin sensitivity, glucose production, and glucose uptake. The dysregulation of one or more of these mechanisms due to environmental and/or genetic factors, can lead to a defective glucose homeostasis. Hyperglycemia is managed by augmenting insulin secretion and/or interaction with hepatic glucose production, as well as by decreasing dietary caloric intake and raising glucose metabolism through exercise. Although these interventions can delay disease progression and correct blood glucose levels, they are not able to cure the disease or stop its progression entirely. Better management of type 2 diabetes is sorely needed. Advances in genotyping techniques and the availability of large patient cohorts have made it possible to identify common genetic variants associated with type 2 diabetes through genome-wide association studies (GWAS). So far, genetic variants on 19 loci have been identified. Most of these loci contain or lie close to genes that were not previously linked to diabetes and they may thus harbor targets for new drugs. It is also hoped that further genetic studies will pave the way for predictive genetic screening. The newly discovered type 2 diabetes genes can be classified based on their presumed molecular function, and we discuss the relation between these gene classes and current treatments. We go on to consider whether the new genes provide opportunities for developing alternative drug therapies

Expressing the Differences between Crohn Disease and Ulcerative Colitis

Wijmenga discusses the implications of a study that used a comprehensive gene expression approach to find new genes and pathways relevant to the pathophysiology of inflammatory bowel disease

Studying the gut virome in the metagenomic era:challenges and perspectives

The human gut harbors a complex ecosystem of microorganisms, including bacteria and viruses. With the rise of next-generation sequencing technologies, we have seen a quantum leap in the study of humangut-inhabiting bacteria, yet the viruses that infect these bacteria, known as bacteriophages, remain underexplored. In this review, we focus on what is known about the role of bacteriophages in human health and the technical challenges involved in studying the gut virome, of which they are a major component. Lastly, we discuss what can be learned from studies of bacteriophages in other ecosystems

NMR Determination of Oligonucleotide Structure

This unit provides an overview of the use of NMR to determine oligonucleotide structure. It covers basic NMR spectral properties, acquisition of interproton distance restraints and torsion angle restraints, structure refinement, assessment of the quality of the structure obtained. Software programs used in the process are also described.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143742/1/cpnc0702.pd

Identification of TUB as a novel candidate gene influencing body weight in humans

Previously, we identified a locus on 11p influencing obesity in families with type 2 diabetes. Based on mouse studies, we selected TUB as a functional candidate gene and performed association studies to determine whether this controls obesity. We analyzed the genotypes of 13 single nucleotide polymorphisms (SNPs) around TUB in 492 unrelated type 2 diabetic patients with known BMI values. One SNP (rs1528133) was found to have a significant effect on BMI (1.54 kg/m(2), P = 0.006). This association was confirmed in a population enriched for type 2 diabetes, using 750 individuals who were not selected for type 2 diabetes. Two SNPs in linkage disequilibrium with rs1528133 and mapping to the 3' end of TUB, rs2272382, and rs2272383 also affected BMI by 1.3 kg/m2 (P = 0.016 and P = 0.010, respectively). Combined analysis confirmed this association (P = 0.005 and P = 0.002, respectively). Moreover, comparing 349 obese subjects (BMI >30 kg/m(2)) from the combined cohort with 289 normal subjects (BMI <25 kg/m(2)) revealed that the protective alleles have a lower frequency in obese subjects (odds ratio 1.32 [95% CI 1.04-1.67], P = 0.022). Altogether, data from the tubby mouse as well as these data suggest that TUB could be an important factor in controlling the central regulation of body weight in humans