Summer eczema in exported Icelandic horses: influence of environmental and genetic factors

A cross sectional study was designed to estimate the prevalence of summer eczema (a chronic, recurrent seasonal dermatitis) in exported Icelandic horses and the influence of environmental and genetic factors on the development of the disease. Among 330 horses, which had been exported to Germany, Denmark and Sweden, 114 (34.5%) were found to have clinical signs of summer eczema. The prevalence was highest 2 years after export and the exposure to the biting midges Culicoides spp., was found to be the main risk factor for developing the disease. Genetic influence on the sensitivity for the disease was not established. It was concluded that exported Icelandic horses are predisposed for summer dermatitis and the fact that they are not introduced to the antigens of the biting midges early in live, due to it's absence in Iceland, is likely to explain the high prevalence of the disease after export

The Wellesley News (12-01-1966)

https://repository.wellesley.edu/wcnews/1090/thumbnail.jp

Identification of candidate pelagic marine protected areas through a seabird seasonal-, multispecific- and extinction risk-based approach

With increasing pressure on the oceans from environmental change, there has been a global call for improved protection of marine ecosystems through the implementation of marine protected areas (MPAs). Here, we used species distribution modelling (SDM) of tracking data from 14 seabird species to identify key marine areas in the southwest Atlantic Ocean, valuing areas based on seabird species occurrence, seasonality and extinction risk. We also compared overlaps between the outputs generated by the SDM and layers representing important human threats (fishing intensity, ship density, plastic and oil pollution, ocean acidification), and calculated loss in conservation value using fishing and ship density as cost layers. The key marine areas were located on the southern Patagonian Shelf, overlapping extensively with areas of high fishing activity, and did not change seasonally, while seasonal areas were located off south and southeast Brazil and overlapped with areas of high plastic pollution and ocean acidification. Non-seasonal key areas were located off northeast Brazil on an area of high biodiversity, and with relatively low human impacts. We found support for the use of seasonal areas depending on the seabird assemblage used, because there was a loss in conservation value for the seasonal compared to the non-seasonal approach when using ‘cost’ layers. Our approach, accounting for seasonal changes in seabird assemblages and their risk of extinction, identified additional candidate areas for incorporation in the network of pelagic MPAs

Incision and aggradation in proglacial rivers: post-Little Ice Age long-profile adjustments of southern Iceland outwash plains

This is the peer reviewed version of the following article: Roussel, R., Marren, P.M., Cossart, E., Toumazet, J-M., Chenet, M., Grancher, D., Jomelli, V. (2018). Incision and aggradation in proglacial rivers: post-Little Ice Age long-profile adjustments of southern Iceland outwash plains. Land Degradation & Development, 29(10), 3753-3771, which has been published in final form at https://doi.org/10.1002/ldr.3127. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-ArchivingThe retreat of glaciers in response to climate warming leads to substantial changes in meltwater and sediment yield. Glacial shrinkage also induces the emergence and growth of proglacial margin landforms which strongly affect water and sedimentary transfers from the glacier to the outwash plains.On a decadal-timescale, field observations show that outwash plains of retreating glaciers typically exhibit proximal incision which decreases in magnitude downstream and stops at an inflection point where aggradation begins. Nevertheless, there is a lack of knowledge about the rates and magnitude of this fluvial adjustment and the effects of the proglacial margin configuration on the temperance or the aggravation of this fluvial adjustment to glacier retreat. This paper investigates the proglacial rivers of 14 retreating glaciers in southeast Iceland over a post-Little Ice Age timescale, combining fluvial deposits mapping, lichenometric dating and long-profile measurements of proglacial fluvial terraces.Our results demonstrate that: (1) proximal incision, associated with distal aggradation and downstream migration of the inflection point is the dominant pattern of proglacial river response to post-LIA glacier retreat in Iceland; (2) estimated mean rates of downstream migration of the inflection point range between 5and 46m.a-1; (3)t he downstream migration rate of the inflection point is positively correlated with the proportion of proglacial lakes within the glacier foreland. These findings suggest that proglacial margins dominated by proglacial lakes intensify the rates of proximal incision and inflection point migration

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

The population genomic legacy of the second plague pandemic

SummaryHuman populations have been shaped by catastrophes that may have left long-lasting signatures in their genomes. One notable example is the second plague pandemic that entered Europe in ca. 1,347 CE and repeatedly returned for over 300 years, with typical village and town mortality estimated at 10%–40%.1 It is assumed that this high mortality affected the gene pools of these populations. First, local population crashes reduced genetic diversity. Second, a change in frequency is expected for sequence variants that may have affected survival or susceptibility to the etiologic agent (Yersinia pestis).2 Third, mass mortality might alter the local gene pools through its impact on subsequent migration patterns. We explored these factors using the Norwegian city of Trondheim as a model, by sequencing 54 genomes spanning three time periods: (1) prior to the plague striking Trondheim in 1,349 CE, (2) the 17th–19th century, and (3) the present. We find that the pandemic period shaped the gene pool by reducing long distance immigration, in particular from the British Isles, and inducing a bottleneck that reduced genetic diversity. Although we also observe an excess of large FST values at multiple loci in the genome, these are shaped by reference biases introduced by mapping our relatively low genome coverage degraded DNA to the reference genome. This implies that attempts to detect selection using ancient DNA (aDNA) datasets that vary by read length and depth of sequencing coverage may be particularly challenging until methods have been developed to account for the impact of differential reference bias on test statistics.Results and discussion STAR★Method

MAP1B mutations cause intellectual disability and extensive white matter deficit

Publisher's version (útgefin grein). Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Discovery of coding variants in genes that confer risk of neurodevelopmental disorders is an important step towards understanding the pathophysiology of these disorders. Wholegenome sequencing of 31,463 Icelanders uncovers a frameshift variant (E712KfsTer10) in microtubule-associated protein 1B (MAP1B) that associates with ID/low IQ in a large pedigree (genome-wide corrected P = 0.022). Additional stop-gain variants in MAP1B (E1032Ter and R1664Ter) validate the association with ID and IQ. Carriers have 24% less white matter (WM) volume (β = −2.1SD, P = 5.1 × 10−8), 47% less corpus callosum (CC) volume (β = −2.4SD, P = 5.5 × 10−10) and lower brain-wide fractional anisotropy (P = 6.7 × 10−4). In summary, we show that loss of MAP1B function affects general cognitive ability through a profound, brain-wide WM deficit with likely disordered or compromised axons.We are grateful to the participants and we thank the psychologists, nurses and staff, in particular Berglind Eiriksdottir, at the Research Recruitment Center and technicians and staff at Röntgen Domus. We also thank the staff at deCODE genetics core facilities and all our colleagues for their important contribution to this work. L.J. received support from the Swedish Society of Medicine, the Swedish Brain Foundation and Swedish Society for Medical Research. The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreements’ no. 115008 (NEWMEDS) and no. 115300 (EUAIMS) of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union’s Seventh Framework Programme (EU-FP7/2007-2013), EU-FP7 funded grant no. 602450 (IMAGEMEND) and EU funded FP7-People-2011-IAPP grant agreement no. 286213 (PsychDPC).Peer Reviewe

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease

Eighty-eight variants highlight the role of T cell regulation and airway remodeling in asthma pathogenesis

Publisher's version (útgefin grein)Asthma is one of the most common chronic diseases affecting both children and adults. We report a genome-wide association meta-analysis of 69,189 cases and 702,199 controls from Iceland and UK biobank. We find 88 asthma risk variants at 56 loci, 19 previously unreported, and evaluate their effect on other asthma and allergic phenotypes. Of special interest are two low frequency variants associated with protection against asthma; a missense variant in TNFRSF8 and 3‘ UTR variant in TGFBR1. Functional studies show that the TNFRSF8 variant reduces TNFRSF8 expression both on cell surface and in soluble form, acting as loss of function. eQTL analysis suggests that the TGFBR1 variant acts through gain of function and together with an intronic variant in a downstream gene, SMAD3, points to defective TGFβR1 signaling as one of the biological perturbations increasing asthma risk. Our results increase the number of asthma variants and implicate genes with known role in T cell regulation, inflammation and airway remodeling in asthma pathogenesis.We thank the individuals who participated in this study and the staff at the Icelandic Patient Recruitment Center and the deCODE genetics core facilities. Further to all our colleagues who contributed to the data collection and phenotypic characterization of clinical samples as well as to the genotyping and analysis of the whole-genome association data. This research has been conducted using the UK biobank Resource under Application Number ‘24711’.Peer Reviewe