Populationsstruktur und genetische Diversität von Schweizer Schafrassen

Das Jahr 2010 wurde von den Vereinten Nationen zum Jahr der Biodiversität erklärt. Der Schweizerische Schafzuchtverband stellte in diesem Kontext Herdebuchdaten der vier grössten Schweizer Schafrassen zur Analyse der genetischen Diversität zur Verfügung. Untersucht wur-den das Braunköpfige Fleischschaf (BFS; n=10 858), das Schwarzbraune Bergschaf (SBS; n=10 964), das Walliser Schwarznasenschaf (SN; n=14 371) und das Weisse Alpenschaf (WAS; n=32 169). Die Analysen beruhen auf allen Herdebuchtieren der Geburtsjahre 1996–2008 und ihren Ahnen bis und mit Geburtsjahr 1970. Ausgewertet wurden die Daten mit gängiger Software für populationsgenetische Fragestellungen. Die grösste Zunahme beim mittleren Inzuchtkoeffizienten konnte im untersuchten Zeitraum bei der Rasse SN (5,9 → 9,3 %) gefolgt von denRassen BFS (2,4 → 4,3 %), SBS (2,4 → 3,8 %) und WAS (1,4 → 2,5 %) beobachtet werden. Obwohl die Inzuchtraten im Zeitraum 1996 bis 2008 teilweise starke Schwankungen aufwiesen, zeigte sich bei allen vier Rassen grundsätzlich ein steigender Trend. Damit einher ging ein sinkender Trend bei der effektiven Populationsgrösse. Die grösste Anzahl an effektiven Gründertieren, Ahnen und Gründergenomen fanden sich beim weissen Alpenschaf. Bei allen vier Rassen war bei diesen drei Parametern im Laufe der Jahre eine sinkende Tendenz erkennbar, wobei die Abnahme bei der Rasse WAS im Vergleich mit den anderen Rassen viel ausgeprägter war. Ein weiterer Indikator für eine abnehmende genetische Vielfalt von 1996 bis 2008 ist der marginale Genanteil des wichtigsten Ahnen. Dieser ist bei allen vier Rassen angestiegen (SN 11,05 → 19,79 %; BFS 7,67 →11,27 %; SBS 4,45 → 5,19 %; WAS 2,84 →4,69 %).Aufgrund der Ergebnisse stellt sich die Frage nach gezielten Managementmassnahmen nur bei der SN-Population. Bei den anderen drei Rassen sollten die Trends der genetischen Diversitäts-parameter jedoch regelmässig überprüft werden

Bioclimatic envelope models predict a decrease in tropical forest carbon stocks with climate change in Madagascar

Recent studies have underlined the importance of climatic variables in determining tree height and biomass in tropical forests. Nonetheless, the effects of climate on tropical forest carbon stocks remain uncertain. In particular, the application of process-based dynamic global vegetation models has led to contrasting conclusions regarding the potential impact of climate change on tropical forest carbon storage. Using a correlative approach based on a bioclimatic envelope model and data from 1771 forest plots inventoried during the period 1996–2013 in Madagascar over a large climatic gradient, we show that temperature seasonality, annual precipitation and mean annual temperature are key variables in determining forest above-ground carbon density. Taking into account the explicative climate variables, we obtained an accurate (R2 = 70% and RMSE = 40 Mg ha−1) forest carbon map for Madagascar at 250 m resolution for the year 2010. This national map was more accurate than previously published global carbon maps (R2 ≤ 26% and RMSE ≥ 63 Mg ha−1). Combining our model with the climatic projections for Madagascar from 7 IPCC CMIP5 global climate models following the RCP 8.5, we forecast an average forest carbon stock loss of 17% (range: 7–24%) by the year 2080. For comparison, a spatially homogeneous deforestation of 0.5% per year on the same period would lead to a loss of 30% of the forest carbon stock. Synthesis. Our study shows that climate change is likely to induce a decrease in tropical forest carbon stocks. This loss could be due to a decrease in the average tree size and to shifts in tree species distribution, with the selection of small-statured species. In Madagascar, climate-induced carbon emissions might be, at least, of the same order of magnitude as emissions associated with anthropogenic deforestation

Ökologische Fallenwirkung von einjährigen Blühstreifen – Laufkäfer als Ökozeiger

Werden Blühstreifen von Nützlingen und Bestäubern als Nistplatz gebraucht, könnte ein Umbrechen zu einer Zerstörung der Nachkommen führen. Dies würde den Blühstreifen zu einer ökologischen Falle machen. In der vorliegenden Studie konnte die Hypothese einer ökologischen Falle für Nützlinge und Bestäuber jedoch nicht bestätigt werden. Es wurden 35 verschiedene Arten Laufkäfer gefangen, sechs davon stehen auf der Roten Liste

Atorvastatin added to interferon beta for relapsing multiple sclerosis: a randomized controlled trial

Statins have anti-inflammatory and immunomodulatory properties in addition to lipid-lowering effects. The present study evaluated the effect of atorvastatin added to interferon beta-1b in multiple sclerosis (MS) in a multicenter, randomized, parallel-group, rater-blinded study performed in eight Swiss hospitals. Seventy-seven patients with relapsing-remitting MS started interferon beta-1b every other day. After 3months, they were randomized 1:1 to receive atorvastatin 40mg/day or not in addition to interferon beta-1b until month 15. The primary endpoint was the proportion of patients with new lesions on T2-weighted images at month 15 compared to baseline at month three. At study end, the proportion of patients with new lesions on T2-weighted images was equal in both groups (odds ratio 1.14; 95% CI 0.36-3.56; p=0.81). All predefined secondary endpoints including number of new lesions and total lesion volume on T2-weighted images, total number of new Gd-enhancing lesions on T1-weighted images, total brain volume, volume of grey matter, volume of white matter, EDSS, MSFC, relapse rate, time to first relapse, number of relapse-free patients and neutralizing antibodies did not show any significant differences (all p values >0.1). Transient elevations of liver enzymes were more frequent with atorvastatin (p=0.02). In conclusion, atorvastatin 40mg/day in addition to interferon beta-1b did not have a beneficial effect on relapsing-remitting MS compared to interferon beta-1b monotherapy over a 12-month perio

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis

Background Rare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes. Methods We did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses. Findings A locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55–2·08], p=5·13×10– ¹⁵) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42–1·71], p=7·65×10– ²⁰) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25–1·48], p=1·69×10– ¹²; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reduced SOX17 expression. The HLA-DPA1/DPB1 rs2856830 genotype was strongly associated with survival. Median survival from diagnosis in patients with pulmonary arterial hypertension with the C/C homozygous genotype was double (13·50 years [95% CI 12·07 to >13·50]) that of those with the T/T genotype (6·97 years [6·02–8·05]), despite similar baseline disease severity. Interpretation This is the first study to report that common genetic variation at loci in an enhancer near SOX17 and in HLA-DPA1/DPB1 is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more common in pulmonary arterial hypertension than suggested by rare mutations in SOX17. Further studies are needed to confirm the association between HLA typing or rs2856830 genotyping and survival, and to determine whether HLA typing or rs2856830 genotyping improves risk stratification in clinical practice or trials. Funding UK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA, ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and RNAS, German DFG, German BMBF, APH Paris, INSERM, Université Paris-Sud, and French ANR