Exome sequencing identified rare recurrent copy number variants and hereditary breast cancer susceptibility.

Copy number variants (CNVs) are a major source of genetic variation and can disrupt genes or affect gene dosage. They are known to be causal or underlie predisposition to various diseases. However, the role of CNVs in inherited breast cancer susceptibility has not been thoroughly investigated. To address this, we performed whole-exome sequencing based analysis of rare CNVs in 98 high-risk Northern Finnish breast cancer cases. After filtering, selected candidate alleles were validated and characterized with a combination of orthogonal methods, including PCR-based approaches, optical genome mapping and long-read sequencing. This revealed three recurrent alterations: a 31 kb deletion co-occurring with a retrotransposon insertion (delins) in RAD52, a 13.4 kb deletion in HSD17B14 and a 64 kb partial duplication of RAD51C. Notably, all these genes encode proteins involved in pathways previously identified as essential for breast cancer development. Variants were genotyped in geographically matched cases and controls (altogether 278 hereditary and 1983 unselected breast cancer cases, and 1229 controls). The RAD52 delins and HSD17B14 deletion both showed significant enrichment among cases with indications of hereditary disease susceptibility. RAD52 delins was identified in 7/278 cases (2.5%, P = 0.034, OR = 2.86, 95% CI = 1.10-7.45) and HSD17B14 deletion in 8/278 cases (2.9%, P = 0.014, OR = 3.28, 95% CI = 1.31-8.23), the frequency of both variants in the controls being 11/1229 (0.9%). This suggests a role for RAD52 and HSD17B14 in hereditary breast cancer susceptibility. The RAD51C duplication was very rare, identified only in 2/278 of hereditary cases and 2/1229 controls (P = 0.157, OR = 4.45, 95% CI = 0.62-31.70). The identification of recurrent CNVs in these genes, and especially the relatively high frequency of RAD52 and HSD17B14 alterations in the Finnish population, highlights the importance of studying CNVs alongside single nucleotide variants when searching for genetic factors underlying hereditary disease predisposition.

Strong Purifying Selection in Haploid Tissue-Specific Genes of Scots Pine Supports the Masking Theory.

The masking theory states that genes expressed in a haploid stage will be under more efficient selection. In contrast, selection will be less efficient in genes expressed in a diploid stage, where the fitness effects of recessive deleterious or beneficial mutations can be hidden from selection in heterozygous form. This difference can influence several evolutionary processes such as the maintenance of genetic variation, adaptation rate, and genetic load. Masking theory expectations have been confirmed in single-cell haploid and diploid organisms. However, in multicellular organisms, such as plants, the effects of haploid selection are not clear-cut. In plants, the great majority of studies indicating haploid selection have been carried out using male haploid tissues in angiosperms. Hence, evidence in these systems is confounded with the effects of sexual selection and intraspecific competition. Evidence from other plant groups is scarce, and results show no support for the masking theory. Here, we have used a gymnosperm Scots pine megagametophyte, a maternally derived seed haploid tissue, and four diploid tissues to test the strength of purifying selection on a set of genes with tissue-specific expression. By using targeted resequencing data of those genes, we obtained estimates of genetic diversity, the site frequency spectrum of 0-fold and 4-fold sites, and inferred the distribution of fitness effects of new mutations in haploid and diploid tissue-specific genes. Our results show that purifying selection is stronger for tissue-specific genes expressed in the haploid megagametophyte tissue and that this signal of strong selection is not an artifact driven by high expression levels.

Taming the massive genome of Scots pine with PiSy50k, a new genotyping array for conifer research.

Pinus sylvestris (Scots pine) is the most widespread coniferous tree in the boreal forests of Eurasia, with major economic and ecological importance. However, its large and repetitive genome presents a challenge for conducting genome-wide analyses such as association studies, genetic mapping and genomic selection. We present a new 50K single-nucleotide polymorphism (SNP) genotyping array for Scots pine research, breeding and other applications. To select the SNP set, we first genotyped 480 Scots pine samples on a 407 540 SNP screening array and identified 47 712 high-quality SNPs for the final array (called 'PiSy50k'). Here, we provide details of the design and testing, as well as allele frequency estimates from the discovery panel, functional annotation, tissue-specific expression patterns and expression level information for the SNPs or corresponding genes, when available. We validated the performance of the PiSy50k array using samples from Finland and Scotland. Overall, 39 678 (83.2%) SNPs showed low error rates (mean = 0.9%). Relatedness estimates based on array genotypes were consistent with the expected pedigrees, and the level of Mendelian error was negligible. In addition, array genotypes successfully discriminate between Scots pine populations of Finnish and Scottish origins. The PiSy50k SNP array will be a valuable tool for a wide variety of future genetic studies and forestry applications.

Selection patterns on early-life phenotypic traits in Pinus sylvestris are associated with precipitation and temperature along a climatic gradient in Europe.

Understanding the dynamics of selection is key to predicting the response of tree species to new environmental conditions in the current context of climate change. However, selection patterns acting on early recruitment stages and their climatic drivers remain largely unknown in most tree species, despite being a critical period of their life cycle. We measured phenotypic selection on Pinus sylvestris seed mass, emergence time and early growth rate over 2 yr in four common garden experiments established along the latitudinal gradient of the species in Europe. Significant phenotypic plasticity and among-population genetic variation were found for all measured phenotypic traits. Heat and drought negatively affected fitness in the southern sites, but heavy rainfalls also decreased early survival in middle latitudes. Climate-driven directional selection was found for higher seed mass and earlier emergence time, while the form of selection on seedling growth rates differed among sites and populations. Evidence of adaptive and maladaptive phenotypic plasticity was found for emergence time and early growth rate, respectively. Seed mass, emergence time and early growth rate have an adaptive role in the early stages of P. sylvestris and climate strongly influences the patterns of selection on these fitness-related traits.

Vegetation on mesic loamy and sandy soils along a 1700-km maritime Eurasia Arctic Transect.

QUESTIONS: How do plant communities on zonal loamy vs. sandy soils vary across the full maritime Arctic bioclimate gradient? How are plant communities of these areas related to existing vegetation units of the European Vegetation Classification? What are the main environmental factors controlling transitions of vegetation along the bioclimate gradient? LOCATION: 1700-km Eurasia Arctic Transect (EAT), Yamal Peninsula and Franz Josef Land (FJL), Russia. METHODS: The Braun-Blanquet approach was used to sample mesic loamy and sandy plots on 14 total study sites at six locations, one in each of the five Arctic bioclimate subzones and the forest-tundra transition. Trends in soil factors, cover of plant growth forms (PGFs) and species diversity were examined along the summer warmth index (SWI) gradient and on loamy and sandy soils. Classification and ordination were used to group the plots and to test relationships between vegetation and environmental factors. RESULTS: Clear, mostly non-linear, trends occurred for soil factors, vegetation structure and species diversity along the climate gradient. Cluster analysis revealed seven groups with clear relationships to subzone and soil texture. Clusters at the ends of the bioclimate gradient (forest-tundra and polar desert) had many highly diagnostic taxa, whereas clusters from the Yamal Peninsula had only a few. Axis 1 of a DCA was strongly correlated with latitude and summer warmth; Axis 2 was strongly correlated with soil moisture, percentage sand and landscape age. CONCLUSIONS: Summer temperature and soil texture have clear effects on tundra canopy structure and species composition, with consequences for ecosystem properties. Each layer of the plant canopy has a distinct region of peak abundance along the bioclimate gradient. The major vegetation types are weakly aligned with described classes of the European Vegetation Checklist, indicating a continuous floristic gradient rather than distinct subzone regions. The study provides ground-based vegetation data for satellite-based interpretations of the western maritime Eurasian Arctic, and the first vegetation data from Hayes Island, Franz Josef Land, which is strongly separated geographically and floristically from the rest of the gradient and most susceptible to on-going climate change.

Sea ice, rain-on-snow and tundra reindeer nomadism in Arctic Russia.

Sea ice loss is accelerating in the Barents and Kara Seas (BKS). Assessing potential linkages between sea ice retreat/thinning and the region's ancient and unique social-ecological systems is a pressing task. Tundra nomadism remains a vitally important livelihood for indigenous Nenets and their large reindeer herds. Warming summer air temperatures have been linked to more frequent and sustained summer high-pressure systems over West Siberia, Russia, but not to sea ice retreat. At the same time, autumn/winter rain-on-snow (ROS) events have become more frequent and intense. Here, we review evidence for autumn atmospheric warming and precipitation increases over Arctic coastal lands in proximity to BKS ice loss. Two major ROS events during November 2006 and 2013 led to massive winter reindeer mortality episodes on the Yamal Peninsula. Fieldwork with migratory herders has revealed that the ecological and socio-economic impacts from the catastrophic 2013 event will unfold for years to come. The suggested link between sea ice loss, more frequent and intense ROS events and high reindeer mortality has serious implications for the future of tundra Nenets nomadism.

Do the classification of areas and distance matter to the assessment results of achieving the treatment targets among type 2 diabetes patients?

BACKGROUND: Type 2 diabetes is a major health concern all over the world. The prevention of diabetes is important but so is well-balanced diabetes care. Diabetes care can be influenced by individual and neighborhood socio-economic factors and geographical accessibility to health care services. The aim of the study is to find out whether two different area classifications of urban and rural areas give different area-level results of achieving the targets of control and treatment among type 2 diabetes patients exemplified by a Finnish region. The study exploits geo-referenced patient data from a regional primary health care patient database combined with postal code area-level socio-economic variables, digital road data and two grid based classifications of areas: an urban-rural dichotomy and a classification with seven area types. METHODS: The achievement of control and treatment targets were assessed using the patient's individual laboratory data among 9606 type 2 diabetes patients. It was assessed whether hemoglobin A1c (HbA1c) was controlled and whether the recommended level of HbA1c was achieved in patients by different area classes and as a function of distance. Chi square test and logistic regression analysis were used for testing. RESULTS: The study reveals that area-level inequalities exist in the care of type 2 diabetes in a detailed 7-class area classification but if the simple dichotomy of urban and rural is applied differences vanish. The patient's gender and age, area-level education and the area class they belonged to were associated with achievements of control and treatment targets. Longer distance to health care services was not a barrier to good achievements of control or treatment targets. CONCLUSIONS: A more detailed grid-based area classification is better for showing spatial differences in the care of type 2 diabetes patients. Inequalities exist but it would be misleading to state that the differences are simply due to urban or rural location or due to distance. From a planning point of view findings suggest that detailed geo-coded patient information could be utilized more in resourcing and targeting the health care services to find the area-level needs of care and to improve the cost-efficient allocation of resources.

Upscaling vascular aboveground biomass and topsoil moisture of subarctic fens from Unoccupied Aerial Vehicles (UAVs) to satellite level.

Arctic and subarctic ecosystems are experiencing rapid changes in vegetation composition and productivity due to global warming. Tundra wetlands are especially susceptible to these changes, which may trigger shifts in soil moisture dynamics. It is therefore essential to accurately map plant biomass and topsoil moisture. In this study, we mapped total, wood, and leaf above ground biomass and topsoil moisture in subarctic tundra wetlands located between Norway and Finland by linking models derived from Unoccupied Aerial Vehicles with multiple satellite data sources using the Extreme Gradient Boosting algorithm. The most accurate predictions for topsoil moisture (R2 = 0.73) used a set of red edge-based vegetation indices with a spatial resolution of 20 m per pixel. On the contrary, wood biomass showed the lowest accuracies across all tested models (R2 = 0.38). We found a trade-off between the spatial resolution and the performance of upscaling models, where smaller pixel sizes generally led to lower accuracies. However, we were able to compensate for reduced accuracy at smaller pixel sizes using Copernicus phenology metrics. A modelling uncertainty assessment revealed that the uncertainty of predictions increased with decreasing pixel sizes and increasing number of co-predictors. Our approach could improve efforts to map and monitor changes in vegetation at regional to pan-Arctic scales.

Within- and between-population comparisons suggest independently acting selection maintaining parallel clines in Scots pine (Pinus sylvestris).

Parallel clines in traits related to adaptation in a species can be due to independent selection on a pair of traits, or due to selection in one trait resulting in a parallel cline in a correlated trait. To distinguish between the mechanisms giving rise to parallel adaptive population divergence of multiple traits along an environmental gradient we need to study variation, correlations, and selective forces within individual populations along the gradient. In many tree species, budset timing (BST) forms a latitudinal cline, and parallel clinal variation is also found in other seedling traits, such as first-year height (FYH) and fall frost injury (FFI). In this study, we set up a common garden experiment with open pollinated progeny from natural populations of Scots pine (Pinus sylvestris), with one large sample from single population (500 families) and smaller samples from across a latitudinal gradient. BST, FYH and induced FFI were first measured in a greenhouse. The seedlings were then planted in the field, where survival and height were measured at the age of 9 years as fitness proxies. We compared between- and within-population variation and genetic correlations of these three seedling traits, and estimated selection gradients at the family level in our main population, taking into account the potential effects of seed weight. Between-population genetic correlations between seedling traits were high (0.76-0.95). Within-population genetic correlations in the main population were lower (0.14-0.35), as in other populations (0.10-0.39). Within population, extensive adaptive variation persists in the seedling traits, in line with rather weak selection gradients, yet maintaining the clines. Although our sampling does not cover the whole cline equally, the results suggest that the individual clines in these traits are maintained by largely independently acting selection, which results in fewer constraints in adaptation under changing climate.

The Arctic Plant Aboveground Biomass Synthesis Dataset.

Plant biomass is a fundamental ecosystem attribute that is sensitive to rapid climatic changes occurring in the Arctic. Nevertheless, measuring plant biomass in the Arctic is logistically challenging and resource intensive. Lack of accessible field data hinders efforts to understand the amount, composition, distribution, and changes in plant biomass in these northern ecosystems. Here, we present The Arctic plant aboveground biomass synthesis dataset, which includes field measurements of lichen, bryophyte, herb, shrub, and/or tree aboveground biomass (g m-2) on 2,327 sample plots from 636 field sites in seven countries. We created the synthesis dataset by assembling and harmonizing 32 individual datasets. Aboveground biomass was primarily quantified by harvesting sample plots during mid- to late-summer, though tree and often tall shrub biomass were quantified using surveys and allometric models. Each biomass measurement is associated with metadata including sample date, location, method, data source, and other information. This unique dataset can be leveraged to monitor, map, and model plant biomass across the rapidly warming Arctic.

Input data resolution affects the conservation prioritization outcome of spatially sparse biodiversity features.

Detailed spatial data are an essential part of land use planning and decision-making. Their spatial resolution sets limitations to their use, as coarse datasets are not suitable for detecting small-scale phenomena. In this study, we explored the effects of spatial resolution on the ecological outcome of a conservation prioritization process in Zonation software. Our study area was in Evo, southern Finland, covering a mosaic of managed and conserved forests. We produced the feature layers describing the forest characteristics using high-resolution remote sensing datasets, object-based mapping methods, and forest site type data. We found that increasing the resolution above the 16 m baseline resolution resulted in substantial errors. The conservation errors were the highest for rare features related to European Aspen, whereas the common features related to dominant tree species could benefit from the growth of cell size. We conclude that adequate spatial resolution is a prerequisite for efficient conservation prioritization, and that the size and spatial distribution of the features affect the resolution requirements.

Utilizing historical maps in identification of long-term land use and land cover changes.

Knowledge in the magnitude and historical trends in land use and land cover (LULC) is needed to understand the changing status of the key elements of the landscape and to better target management efforts. However, this information is not easily available before the start of satellite campaign missions. Scanned historical maps are a valuable but underused source of LULC information. As a case study, we used U-Net to automatically extract fields, mires, roads, watercourses, and water bodies from scanned historical maps, dated 1965, 1984 and 1985 for our 900 km[Formula: see text] study area in Southern Finland. We then used these data, along with the topographic databases from 2005 and 2022, to quantify the LULC changes for the past 57 years. For example, the total area of fields decreased by around 27 km[Formula: see text], and the total length of watercourses increased by around 2250 km in our study area.

Optical Genome Mapping as an Alternative to FISH-Based Cytogenetic Assessment in Chronic Lymphocytic Leukemia.

The fluorescence in situ hybridization (FISH) technique plays an important role in the risk stratification and clinical management of patients with chronic lymphocytic leukemia (CLL). For genome-wide analysis, FISH needs to be complemented with other cytogenetic methods, including karyotyping and/or chromosomal microarrays. However, this is often not feasible in a diagnostic setup. Optical genome mapping (OGM) is a novel technique for high-resolution genome-wide detection of structural variants (SVs), and previous studies have indicated that OGM could serve as a generic cytogenetic tool for hematological malignancies. Herein, we report the results from our study evaluating the concordance of OGM and standard-of-care FISH in 18 CLL samples. The results were fully concordant between these two techniques in the blinded comparison. Using in silico dilution series, the lowest limit of detection with OGM was determined to range between 3 and 9% variant allele fractions. Genome-wide analysis by OGM revealed additional (>1 Mb) aberrations in 78% of the samples, including both unbalanced and balanced SVs. Importantly, OGM also enabled the detection of clinically relevant complex karyotypes, undetectable by FISH, in three samples. Overall, this study demonstrates the potential of OGM as a first-tier cytogenetic test for CLL and as a powerful tool for genome-wide SV analysis.

Truncating TINF2 p.Tyr312Ter variant and inherited breast cancer susceptibility.

TINF2 is a critical subunit of the shelterin complex, which protects and maintains the length of telomeres. Pathogenic missense and truncating TINF2 mutations are causative for dyskeratosis congenita (DC), a rare, dominantly inherited bone marrow failure syndrome characterized by mucocutaneous abnormalities and cancer predisposition. Recent reports indicate that specific TINF2 truncating mutations act as high penetrance cancer predisposition alleles outside DC context, including breast cancer in their tumor spectrum. Here, we have evaluated the role of germline mutations in TINF2 and other shelterin genes in inherited breast cancer susceptibility using exome sequencing data from 98 Northern Finnish breast cancer cases with indication of inherited disease predisposition as a discovery cohort. A single protein truncating variant, TINF2 p.Tyr312Ter, was identified in one of the cases (1/98), and four more carriers were observed in the subsequently genotyped unselected breast cancer cohort (4/1904). None of the carriers were reported to have DC. TINF2 p.Tyr312Ter resulted in stable short form of mRNA transcript, and normal telomere length has been indicated by a recent report. Although recurrent in cases (total of 5/2095), TINF2 p.Tyr312Ter is also present in Finnish population controls (8/12,517), and the observed 4-fold higher frequency in cases falls at most into the range of moderate breast cancer risk alleles (OR 3.74, 95% CI 1.22-11.45, p = 0.029). Current results indicate that not all TINF2 truncating variants are high cancer risk alleles and add further evidence that different TINF2 mutations can have very diverse effects on the disease phenotype.

Evaluating the role of CHEK2 p.(Asp438Tyr) allele in inherited breast cancer predisposition.

CHEK2 is a well-established breast cancer susceptibility gene. The most frequent pathogenic CHEK2 variant is 1100delC, a loss-of-function mutation conferring 2-fold risk for breast cancer. This gene also harbors other rare variants encountered in the clinical gene panels for hereditary cancer. One of these is CHEK2 c.1312 G > T, p.(Asp438Tyr) in the kinase domain of the protein, but due to its rarity its clinical significance for breast cancer predisposition has remained unclear. Here, we tested the prevalence of CHEK2 p.(Asp438Tyr) allele showing enrichment in the Northern Finnish population, in a total of 2284 breast cancer patients from this geographical region. Genotyping was performed for DNA samples extracted from peripheral blood using high-resolution melt analysis. Fourteen CHEK2 p.(Asp438Tyr) carriers were identified (14/2284, 0.6%, P = 0.67): two in the cohort of breast cancer cases with the indication of inherited disease susceptibility (2/281, 0.7%, P = 1.00) and twelve in the breast cancer cohort unselected for the family history of disease and age at disease onset (12/2003, 0.6%, P = 0.66). This frequency did not differ from the frequency in the general population (10/1299, 0.8%). No CHEK2 p.(Asp438Tyr) homozygotes were identified. Our results indicate that CHEK2 p.(Asp438Tyr) carriers do not have an increased risk for breast cancer and the classification of the CHEK2 p.(Asp438Tyr) variant can be changed from the variant of uncertain significance (VUS) to likely benign for breast cancer.

High resilience in the Yamal-Nenets social-ecological system, West Siberian Arctic, Russia.

Tundra ecosystems are vulnerable to hydrocarbon development, in part because small-scale, low-intensity disturbances can affect vegetation, permafrost soils, and wildlife out of proportion to their spatial extent. Scaling up to include human residents, tightly integrated arctic social-ecological systems (SESs) are believed similarly susceptible to industrial impacts and climate change. In contrast to northern Alaska and Canada, most terrestrial and aquatic components of West Siberian oil and gas fields are seasonally exploited by migratory herders, hunters, fishers, and domesticated reindeer (Rangifer tarandus L.). Despite anthropogenic fragmentation and transformation of a large proportion of the environment, recent socioeconomic upheaval, and pronounced climate warming, we find the Yamal-Nenets SES highly resilient according to a few key measures. We detail the remarkable extent to which the system has successfully reorganized in response to recent shocks and evaluate the limits of the system's capacity to respond. Our analytical approach combines quantitative methods with participant observation to understand the overall effects of rapid land use and climate change at the level of the entire Yamal system, detect thresholds crossed using surrogates, and identify potential traps. Institutional constraints and drivers were as important as the documented ecological changes. Particularly crucial to success is the unfettered movement of people and animals in space and time, which allows them to alternately avoid or exploit a wide range of natural and anthropogenic habitats. However, expansion of infrastructure, concomitant terrestrial and freshwater ecosystem degradation, climate change, and a massive influx of workers underway present a looming threat to future resilience.

Accelerated vegetation succession but no hydrological change in a boreal fen during 20 years of recent climate change.

Northern mires (fens and bogs) have significant climate feedbacks and contribute to biodiversity, providing habitats to specialized biota. Many studies have found drying and degradation of bogs in response to climate change, while northern fens have received less attention. Rich fens are particularly important to biodiversity, but subject to global climate change, fen ecosystems may change via direct response of vegetation or indirectly by hydrological changes. With repeated sampling over the past 20 years, we aim to reveal trends in hydrology and vegetation in a pristine boreal fen with gradient from rich to poor fen and bog vegetation. We resampled 203 semi-permanent plots and compared water-table depth (WTD), pH, concentrations of mineral elements, and dissolved organic carbon (DOC), plant species occurrences, community structure, and vegetation types between 1998 and 2018. In the study area, the annual mean temperature rose by 1.0°C and precipitation by 46 mm, in 20-year periods prior to sampling occasions. We found that wet fen vegetation decreased, while bog and poor fen vegetation increased significantly. This reflected a trend of increasing abundance of common, generalist hummock species at the expense of fen specialist species. Changes were the most pronounced in high pH plots, where Sphagnum mosses had significantly increased in plot frequency, cover, and species richness. Changes of water chemistry were mainly insignificant in concentration levels and spatial patterns. Although indications toward drier conditions were found in vegetation, WTD had not consistently increased, instead, our results revealed complex dynamics of WTD as depending on vegetation changes. Overall, we found significant trend in vegetation, conforming to common succession pattern from rich to poor fen and bog vegetation. Our results suggest that responses intrinsic to vegetation, such as increased productivity or altered species interactions, may be more significant than indirect effects via local hydrology to the ecosystem response to climate warming.

Exome sequencing identifies a recurrent variant in SERPINA3 associating with hereditary susceptibility to breast cancer.

BACKGROUND: Breast cancer is strongly influenced by hereditary risk factors. Yet, the known susceptibility genes and genomic loci explain only about half of the familial component of the disease. To identify novel breast cancer predisposing gene defects, here we have performed massive parallel sequencing for Northern Finnish breast cancer cases. METHODS: Ninety-eight breast cancer cases with indication of hereditary disease susceptibility were exome sequenced. Data filtering strategy focused on predictably deleterious rare variants that were still enriched in the sequenced cohort. Findings were confirmed with additional, geographically matched breast cancer cohorts. RESULTS: A recurrent heterozygous splice acceptor variant, c.918-1G>C, in SERPINA3, was identified, and it was significantly enriched both in the hereditary (6/201, 3.0%, p = 0.006, OR 5.1, 95% CI 1.7-14.8) and unselected breast cancer cohort (26/1569, 1.7%, p = 0.009, OR 2.8, 95% CI 1.3-6.2). SERPINA3 c.918-1G>C carriers were also significantly more likely to have a rare tumor subtype, medullary breast cancer, than the non-carriers (4/26, 15.4%, p = 0.000014, OR 42.9, 95% CI 11.7-157.1). CONCLUSION: These findings demonstrate that c.918-1G>C germline variant in SERPINA3 gene, encoding a member of the serine protease inhibitor class, is a novel breast cancer predisposing allele.

Detection of snow surface thawing and refreezing in the Eurasian Arctic with QuikSCAT: implications for reindeer herding.

Snow conditions play an important role for reindeer herding. In particular, the formation of ice crusts after rain-on-snow (ROS) events or general surface thawing with subsequent refreezing impedes foraging. Such events can be monitored using satellite data. A monitoring scheme has been developed for observation at the circumpolar scale based on data from the active microwave sensor SeaWinds on QuikSCAT (Ku-band), which is sensitive to changes on the snow surface. Ground observations on Yamal Peninsula were used for algorithm development. Snow refreezing patterns are presented for northern Eurasia above 60 degrees N from autumn 2001 to spring 2008. Western Siberia is more affected than Central and Eastern Siberia in accordance with climate data, and most events occur in November and April. Ice layers in late winter have an especially negative effect on reindeer as they are already weakened. Yamal Peninsula is located within a transition zone between high and low frequency of events. Refreezing was observed more than once a winter across the entire peninsula during recent years. The southern part experienced refreezing events on average four times each winter. Currently, herders can migrate laterally or north-south, depending on where and when a given event occurs. However, formation of ice crusts in the northern part of the peninsula may become as common as they are now in the southern part. Such a development would further constrain the possibility to migrate on the peninsula.

Evaluating the role of NTHL1 p.Q90* allele in inherited breast cancer predisposition.

BACKGROUND: Rare protein truncating variants of NTHL1 gene are causative for the recently described, recessively inherited NTHL1 tumor syndrome that is characterized by an increased lifetime risk for colorectal cancer, colorectal polyposis, and breast cancer. Although there is strong evidence for breast cancer being a part of the cancer spectrum in these families, the role of pathogenic NTHL1 variants in breast cancer susceptibility in general population remains unclear. METHODS: We tested the prevalence of NTHL1 nonsense variant c.268C>T, p.Q90*, which is the major allele in NTHL1 families and also shows enrichment in the Finnish population, in a total of 1333 breast cancer patients. Genotyping was performed for DNA samples extracted from peripheral blood by using high-resolution melt analysis. RESULTS: Sixteen NTHL1 p.Q90* heterozygous carriers were identified (1.2%, p = 0.61): 5 in hereditary cohort (n = 234, 2.1%, p = 0.39) and 11 in unselected cohort (n = 1099, 1.0%, p = 0.36). This frequency is equal to that in the general population (19/1324, 1.4%). No NTHL1 p.Q90* homozygotes were identified. CONCLUSION: Our results indicate that NTHL1 p.Q90* heterozygous carriers do not have an increased risk for breast cancer and that the variant is unlikely to be a significant contributor to breast cancer risk at the population level.