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.

Work exposures and mental and musculoskeletal symptoms in organic farming.

This study focussed on harmful exposures and mental and musculoskeletal symptoms in organic and conventional farming using interview data of Finnish farmers over the winter of 2014-2015. The data consisted of 2,169 full-time farmers, out of whom 231 (11%) practiced organic farming and 1,938 (89%) conventional farming. Exposure to poisonous and irritating substances was less frequent while exposures to vibration and mould ('smell of root cellar') were more frequent on organic farms. Mental and musculoskeletal symptoms were slightly more common among organic farmers, but the associations were not statistically significant in regression modelling. Risk factors for mental symptoms included animal production, hired labour, female gender, constant hurry, working alone, economic uncertainty, and inadequate recovery from workdays. Risk factors for musculoskeletal symptoms included older age, female gender, constant hurry, economic uncertainty, difficult working postures, heavy lifting and carrying, and inadequate recovery. Workload and recovery, managing the transition period and better follow-up of the occupational well-being were identified as concerns among organic farmers. Practitioner summary: Converting from conventional to organic farming has become increasingly common. Farmer interviews indicated that exposure to poisonous and irritating substances was less frequent while exposures to vibration and mould were more frequent on organic farms. Mental and musculoskeletal symptoms and risk factors were similar in both types of farming.

Predictors of New Airway Obstruction - An 11 Year's Population-Based Follow-Up Study.

In the present study we aimed to investigate the incidence and predictors of spirometry based airway obstruction in a representative population-based sample. Altogether 3,863 subjects, 1,651 males and 2,212 females aged ≥30 years had normal spirometry in year 2000. Fifty-three percent of them were never and 23% current smokers. A re-spirometry was performed 11 years later. Several characteristics, such as level of education, use of alcohol, physical activity, diet using Alternate healthy eating (AHEI) index, body mass index, circumwaist, sensitive C reactive protein (CRP) and cotinine of the laboratory values and co-morbidities including asthma, allergic rhinitis, sleep apnoea and chronic bronchitis, as potential risk factors for airway obstruction were evaluated. Using forced expiratory volume in one second/ forced vital capacity below the lower limit of normal, we observed 124 new cases of airway obstruction showing a cumulative 11-year incidence of 3.2% and corresponding to an incidence rate of 5.6/1,000 per year (PY). The incidence rate was higher in men than in women (6.3/1,000 PY vs. 5.0/1,000 PY, respectively). The strongest risk factors were current smoking (Odds ratio [OR] 2.5) and previously diagnosed asthma (OR 2.1). Sensitive CRP associated with the increased risk and high AHEI index with the decreased risk of airway obstruction. Using the similar study approach our findings on the incidence of airway obstruction are in line with the previously published figures in Europe. We were able to confirm the recent findings on the protective effect of healthy diet.

Genome-Wide Analysis of Colonization History and Concomitant Selection in Arabidopsis lyrata.

The high climatic variability in the past hundred thousand years has affected the demographic and adaptive processes in many species, especially in boreal and temperate regions undergoing glacial cycles. This has also influenced the patterns of genome-wide nucleotide variation, but the details of these effects are largely unknown. Here we study the patterns of genome-wide variation to infer colonization history and patterns of selection of the perennial herb species Arabidopsis lyrata, in locally adapted populations from different parts of its distribution range (Germany, UK, Norway, Sweden, and USA) representing different environmental conditions. Using site frequency spectra based demographic modeling, we found strong reduction in the effective population size of the species in general within the past 100,000 years, with more pronounced effects in the colonizing populations. We further found that the northwestern European A. lyrata populations (UK and Scandinavian) are more closely related to each other than with the Central European populations, and coalescent based population split modeling suggests that western European and Scandinavian populations became isolated relatively recently after the glacial retreat. We also highlighted loci showing evidence for local selection associated with the Scandinavian colonization. The results presented here give new insights into postglacial Scandinavian colonization history and its genome-wide effects.

Airway obstruction and the risk of myocardial infarction and death from coronary heart disease: a national health examination survey with a 33-year follow-up period.

Chronic obstructive pulmonary disease (COPD) has been associated with coronary mortality. Yet, data about the association between COPD and acute myocardial infarction (MI) remain scarce. We aimed to study airway obstruction as a predictor of MI and coronary mortality among 5576 Finnish adults who participated in a national health examination survey between 1978 and 1980. Subjects underwent spirometry, had all necessary data, showed no indications of cardiovascular disease at baseline, and were followed up through record linkage with national registers through 2011. The primary outcome consisted of a major coronary event-that is, hospitalization for MI or coronary death, whichever occurred first. We specified obstruction using the lower limit of normal categorization. Through multivariate analysis adjusted for potential confounding factors for coronary heart disease, hazard ratios (HRs) (with the 95% confidence intervals in parentheses) of a major coronary event, MI, and coronary death reached 1.06 (0.79-1.42), 0.84 (0.54-1.31), and 1.40 (1.04-1.88), respectively, in those with obstruction compared to others. However, in women aged 30-49 obstruction appeared to predict a major coronary event, where the adjusted HR reached 4.21 (1.73-10.28). In conclusion, obstruction appears to predict a major coronary event in younger women only, whereas obstruction closely associates with the risk of coronary death independent of sex and age.

Role of seed germination in adaptation and reproductive isolation in Arabidopsis lyrata.

Seed germination is an important developmental and life history stage. Yet, the evolutionary impact of germination has mainly been studied in the context of dormancy, or for its role in reproductive isolation between species. Here, we aim to examine multiple consequences of genetic divergence on germination traits between two Arabidopsis lyrata subspecies: ssp. petraea (Eurasia) and ssp. lyrata (North America). Postdormancy germination time, a potentially adaptive trait, showed differentiation between the populations, and quantitative trait loci (QTL) mapping revealed that the trait variation is mainly controlled by two antagonistic loci. These QTL areas contain several candidate genes with known function in postdormancy germination in A. thaliana. The sequence variation of three genes was consistent with differential selection, and they also included fixed nonsynonymous substitutions with potential to account for the phenotypic differentiation. We further show that the divergence between the subspecies has led to a slight but significant reduction in hybrid germination proportions, indicating incipient reproductive isolation. Comparison of reciprocal F1 and F2 progenies suggests that Bateson-Dobzhansky-Muller incompatibilities likely act through uniparentally inherited factors. Examination of genomewide transmission ratio distortion further revealed that cytonuclear interactions cause substantial pregermination inviability in the hybrids. These results confirm that seed germination has adaptive potential beyond the dormancy stage and that hybrid seed inviability can be one of the first reproductive barriers to arise during divergence.

Tuberculosis, Airway Obstruction and Mortality in a Finnish Population.

There is little long-term follow-up data concerning the association between past pulmonary tuberculosis (TB), airway obstruction and mortality. We aimed to analyse a national health examination survey data from 6701 adult Finns undergoing spirometry between 1978 and 1980 (follow-up through 2013). We identified TB either through a disease history or by a TB-indicative scar on a chest x-ray. We specified obstruction using the lower limit of normal (LLN) and classified severity using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1-4. After adjusting for smoking and other confounders, past TB associated with obstruction. Compared to non-TB patients, the adjusted odds ratio (OR; 95% CI) of obstruction reached 2.21 (1.52-3.21) among patients with a scar recorded by one radiologist, 2.48 (1.63-3.78) when recorded by both radiologists and 4.59 (2.86-7.37) among patients with a disease history. Among those with neither past TB nor obstruction, with past TB only, with an obstruction only and with both, we found hazard ratios (HRs; 95% CIs) for subsequent mortality of 1.00 (reference), 1.11 (1.03-1.20), 1.62 (1.31-2.00) and 1.77 (1.45-2.16), adjusted for age, gender, smoking, body mass index (BMI), physical activity, education and general health. In conclusion, past TB strongly determines obstruction, although on its own quite weakly predicts premature death. TB and obstruction combined predict an additive mortality pattern.

Selection for population-specific adaptation shaped patterns of variation in the photoperiod pathway genes in Arabidopsis lyrata during post-glacial colonization.

Spatially varying selection can lead to population-specific adaptation, which is often recognized at the phenotypic level; however, the genetic evidence is weaker in many groups of organisms. In plants, environmental shifts that occur due to colonization of a novel environment may require adaptive changes in the timing of growth and flowering, which are often governed by location-specific environmental cues such as day length. We studied locally varying selection in 19 flowering time loci in nine populations of the perennial herb Arabidopsis lyrata, which has a wide but patchy distribution in temperate and boreal regions of the northern hemisphere. The populations differ in their recent population demographic and colonization histories and current environmental conditions, especially in the growing season length. We searched for population-specific molecular signatures of directional selection by comparing a set of candidate flowering time loci with a genomic reference set within each population using multiple approaches and contrasted the patterns of different populations. The candidate loci possessed approximately 20% of the diversity of the reference loci. On average the flowering time loci had more rare alleles (a smaller Tajima's D) and an excess of highly differentiated sites relative to the reference, suggesting positive selection. The strongest signal of selection was detected in photoperiodic pathway loci in the colonizing populations of Northwestern Europe, whereas no evidence of positive selection was detected in the Central European populations. These findings emphasized the population-specific nature of selection and suggested that photoperiodic adaptation was important during postglacial colonization of the species.

Mortality of asthma, COPD, and asthma-COPD overlap during an 18-year follow up.

BACKGROUND: We studied asthma, COPD, and asthma-COPD overlap (ACO) to predict mortality in a cohort of Finnish adults with an 18-year follow up. METHODS: A national health examination survey representing Finnish adults aged ≥30 years was performed in 2000-2001. The study cohort included 5922 participants (73.8% of the sample) with all relevant data, including a comprehensive clinical examination and spirometry. These participants were followed continuously from baseline until end of 2018 for total, cardiovascular, cancer, and respiratory mortality through a record linkage. Asthma, COPD, and ACO were defined based on the survey data, including spirometry and register data. There were three separate groups of obstructive subjects (one definition excluding the others). RESULTS: Asthma and COPD were significantly associated with higher total mortality in Cox's model adjusted for sex, age, smoking, education level, BMI, leisure time physical activity, cardiovascular disease, diabetes, and hypertension. Hazard ratios (HR) (95% confidence interval [CI]) for asthma, COPD, and ACO were 1.29 (1.05-1.58), 1.50 (1.20-1.88), and 1.26 (0.97-1.65), respectively. Additionally, asthma (HR 1.47, 95% CI 1.09-1.97) and COPD (HR 1.53, 95% CI 1.08-2.16) were associated with cardiovascular mortality. Although ACO did not predict mortality in the whole cohort, there was a significant association with mortality risk among those with hs-CRP 1-2.99 mg/l. CONCLUSIONS: Asthma or COPD predicts higher total mortality and premature death from cardiovascular diseases.

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.

Contrasting healthcare costs of COPD and asthma in elderly.

BACKGROUND: Caring for ageing populations creates new challenges for society. Obstructive pulmonary diseases, asthma and especially COPD, are responsible for considerable morbidity, mortality, and financial costs in the elderly. We present the change in the burden of asthma and COPD in those aged ≥60 years in Finland from 1996 to 2018. METHODS: We collected national register data from 1996 to 2018 from Statistics Finland, Care Register for Health Care, and the Social Insurance Institution. We estimated the prevalence of asthma and severe COPD, use of healthcare, social services, reimbursed inhalation medications, and societal costs. RESULTS: In subjects aged ≥60 years, the prevalence was 8% for asthma with reimbursed medication and 0·7% for severe COPD in 2018. In 1996-2018, total costs increased from 33 M€ to 58 M€ (+57%) for asthma and decreased from 38 M€ to 30 M€ (-27%) for COPD. Costs per patient decreased for asthma from 720 € to 460 € (-57%) and remained stable for COPD (2700 € in 2018). Potential years of life lost (PYLL) increased in COPD from 5000 to 6400 (+28%) and the number of emergency department visits increased from 3700 to 6000 (+62%). CONCLUSIONS: In a population aged ≥60 years, the total burden caused by asthma decreased but remained stable and high in COPD. PYLL and visits in emergency care increased in COPD.

Genetic continuity, isolation, and gene flow in Stone Age Central and Eastern Europe.

The genomic landscape of Stone Age Europe was shaped by multiple migratory waves and population replacements, but different regions do not all show similar patterns. To refine our understanding of the population dynamics before and after the dawn of the Neolithic, we generated and analyzed genomic sequence data from human remains of 56 individuals from the Mesolithic, Neolithic, and Eneolithic across Central and Eastern Europe. We found that Mesolithic European populations formed a geographically widespread isolation-by-distance zone ranging from Central Europe to Siberia, which was already established 10,000 years ago. We found contrasting patterns of population continuity during the Neolithic transition: people around the lower Dnipro Valley region, Ukraine, showed continuity over 4000 years, from the Mesolithic to the end of the Neolithic, in contrast to almost all other parts of Europe where population turnover drove this cultural change, including vast areas of Central Europe and around the Danube River.

Orthologous genes identified by transcriptome sequencing in the spider genus Stegodyphus.

BACKGROUND: The evolution of sociality in spiders involves a transition from an outcrossing to a highly inbreeding mating system, a shift to a female biased sex ratio, and an increase in the reproductive skew among individuals. Taken together, these features are expected to result in a strong reduction in the effective population size. Such a decline in effective population size is expected to affect population genetic and molecular evolutionary processes, resulting in reduced genetic diversity and relaxed selective constraint across the genome. In the genus Stegodyphus, permanent sociality and regular inbreeding has evolved independently three times from periodic-social (outcrossing) ancestors. This genus is therefore an ideal model for comparative studies of the molecular evolutionary and population genetic consequences of the transition to a regularly inbreeding mating system. However, no genetic resources are available for this genus. RESULTS: We present the analysis of high throughput transcriptome sequencing of three Stegodyphus species. Two of these are periodic-social (Stegodyphus lineatus and S.tentoriicola) and one is permanently social (S. mimosarum). From non-normalized cDNA libraries, we obtained on average 7,000 putative uni-genes for each species. Three-way orthology, as predicted from reciprocal BLAST, identified 1,792 genes that could be used for cross-species comparison. Open reading frames (ORFs) could be deduced from 1,345 of the three-way alignments. Preliminary molecular analyses suggest a five- to ten-fold reduction in heterozygosity in the social S. mimosarum compared with the periodic-social species. Furthermore, an increased ratio of non-synonymous to synonymous polymorphisms in the social species indicated relaxed efficiency of selection. However, there was no sign of relaxed selection on the phylogenetic branch leading to S. mimosarum. CONCLUSIONS: The 1,792 three-way ortholog genes identified in this study provide a unique resource for comparative studies of the eco-genomics, population genetics and molecular evolution of repeated evolution of inbreeding sociality within the Stegodyphus genus. Preliminary analyses support theoretical expectations of depleted heterozygosity and relaxed selection in the social inbreeding species. Relaxed selection could not be detected in the S. mimosarum lineage, suggesting that there has been a recent transition to sociality in this species.

Environmental Substances Associated with Chronic Obstructive Pulmonary Disease-A Scoping Review.

Chronic obstructive pulmonary disease (COPD) is a slowly developing non-communicable disease (NCD), causing non-reversible obstruction and leading to marked morbidity and mortality. Besides traditional risk factors such as smoking, some environmental substances can augment the risk of COPD. The European Human Biomonitoring Initiative (HBM4EU) is a program evaluating citizens' exposure to various environmental substances and their possible health impacts. Within the HBM4EU, eighteen priority substances or substance groups were chosen. In this scoping review, seven of these substances or substance groups are reported to have an association or a possible association with COPD. Main exposure routes, vulnerable and high-exposure risk groups, and matrices where these substances are measured are described. Pesticides in general and especially organophosphate and carbamate insecticides, and some herbicides, lead (Pb), and polycyclic aromatic hydrocarbons (PAHs) showed an association, and cadmium (Cd), chromium (Cr and CrVI), arsenic (As), and diisocyanates, a possible association with COPD and/or decreased lung function. Due to long latency in COPD's disease process, the role of chemical exposure as a risk factor for COPD is probably underestimated. More research is needed to support evidence-based conclusions. Generally, chemical exposure is a growing issue of concern, and prompt action is needed to safeguard public health.

Changes in the societal burden caused by sleep apnoea in Finland from 1996 to 2018: A national registry study.

BACKGROUND: In the current century, sleep apnoea has become a significant public health problem due to the obesity epidemic. To increase awareness, improve diagnostics, and improve treatment, Finland implemented a national sleep apnoea programme from 2002 to 2010. Here, we present changes in the societal burden caused by sleep apnoea from 1996 to 2018. METHODS: National register data were collected from the Care Register for Health Care, Statistics Finland, the Social Insurance Institution of Finland, and the Finnish Centre for Pensions. Disease prevalence, use of healthcare and social services, and societal costs were estimated. FINDINGS: The number of sleep apnoea patients increased in secondary care from 8 600 in 1996 to 61 000 in 2018. There was a continuous increase in outpatient visits in secondary care from 9 700 in 1996 to 122 000 in 2018 (1 160%) and in primary care from 10 000 in 2015 to 29 000 in 2018 (190%). Accordingly, the cumulative annual number of days off work for sleep apnoea increased from 1 100 to 46 000. However, disability pensions for sleep apnoea decreased from 820 to 550 (33%) during the observation period. Societal costs per patient decreased over 50% during the observation period (€2 800 to €1 200). INTERPRETATION: The number of sleep apnoea patients in Finland increased remarkably during the observation period. To control this burden, diagnostic methods and treatment were revised and follow up was reorganised. Consequently, there was a significant decrease in societal costs per patient. The decrease in disability pensions suggests earlier diagnosis and improved treatment. The national sleep apnoea programme was one of the initiators for these improved outcomes. FUNDING: The Finnish Institute for Health and Welfare and the Hospital District of Helsinki and Uusimaa (HUH), Helsinki, Finland.

New model species for arctic-alpine plant molecular ecology.

Arctic and alpine, high latitude and high elevation environments are one of the most stressful environments for species to inhabit. This harshness manifests itself in lower species richness in comparison to more southern vegetation zones (Francis & Currie, 2003). Furthermore, the climatic oscillations-past and predicted-have the most dramatic effect on these ecosystems. For example, in regions of continental ice sheets-the northernmost part of Western Europe and North America-the Arctic species assemblages are no older than a few thousands of years, which is a relatively short period from an evolutionary perspective. Although similar environments may have existed further south during the Ice Age, allowing some preadaptation for the Arctic species, the current habitat is a unique combination of environmental factors such as the climate, soil, bedrock, and photoperiod. Hence, understanding the evolutionary forces shaping Arctic-alpine species will be important for predicting these vulnerable environments' population viability and adaptive potential in the future. In this issue of Molecular Ecology Resources, Nowak et al. (Molecular Ecology Resources) present extensive genome-wide resources for an Arctic-alpine plant Draba nivalis. This adds a valuable new member into the cabbage family models for evolutionary genetics and adaptation studies, to accompany e.g., Arabidopsis (Nature Genetics, 43, 476; Nature, 408, 796), Arabis (Nature Plants, 1, 14023) and Capsella (Nature Genetics, 45, 831). A whole new avenue will open up for molecular ecological studies not only for D. nivalis, but the whole large Draba genus with its diverse ecological and evolutionary characteristics.

Scoping Review-The Association between Asthma and Environmental Chemicals.

Asthma is one of the most common chronic diseases worldwide affecting all age groups from children to the elderly. In addition to other factors such as smoking, air pollution and atopy, some environmental chemicals are shown or suspected to increase the risk of asthma, exacerbate asthma symptoms and cause other respiratory symptoms. In this scoping review, we report environmental chemicals, prioritized for investigation in the European Human Biomonitoring Initiative (HBM4EU), which are associated or possibly associated with asthma. The substance groups considered to cause asthma through specific sensitization include: diisocyanates, hexavalent chromium Cr(VI) and possibly p-phenylenediamine (p-PDA). In epidemiological studies, polyaromatic hydrocarbons (PAHs) and organophosphate insecticides are associated with asthma, and phthalates, per- and polyfluoroalkyl substances (PFASs), pyrethroid insecticides, mercury, cadmium, arsenic and lead are only potentially associated with asthma. As a conclusion, exposure to PAHs and some pesticides are associated with increased risk of asthma. Diisocyanates and Cr(VI) cause asthma with specific sensitization. For many environmental chemicals, current studies have provided contradicting results in relation to increased risk of asthma. Therefore, more research about exposure to environmental chemicals and risk of asthma is needed.