Y-chromosome analysis recapitulates key events of Mediterranean populations.

The remarkable geographical situation of the Mediterranean region, located between Europe, Africa, and Asia, with numerous migratory routes, has made this area a crucible of cultures. Studying the Y-chromosome variability is a very performant tool to explore the genetic ancestry and evaluate scenarios that may explain the current Mediterranean gene pool. Here, six Mediterranean populations, including three Balearic Islands (Ibiza, Majorca, and Minorca) and three Southern Italian regions (Catanzaro, Cosenza, and Reggio di Calabria) were typed using 23 Y-STR loci and up to 39 Y-SNPs and compared to geographically targeted key reference populations to explore their genetic relationship and provide an overview of Y-chromosome variation across the Mediterranean basin. Pairwise RST genetic distances calculated with STRs markers and Y-haplogroups mirror the West to East geographic distribution of European and Asian Mediterranean populations, highlighting the North-South division of Italy, with a higher Eastern Mediterranean component in Southern Italian populations. In contrast, the African populations from the Southern coast of the Mediterranean clustered separately. Overall, these results support the notion that migrations from Magna Graecia or the Byzantine Empire, which followed similar Neolithic and post-Neolithic routes into Southern Italy, may have contributed to maintaining and/or reinforcing the Eastern Mediterranean genetic component in Southern Italian populations.

Perceptions of change in the environment caused by the COVID-19 pandemic: Implications for environmental policy.

COVID-19 lockdown measures have impacted the environment with both positive and negative effects. However, how human populations have perceived such changes in the natural environment and how they may have changed their daily habits have not been yet thoroughly evaluated. The objectives of this work were to investigate (1) the social perception of the environmental changes produced by the COVID-19 pandemic lockdown and the derived change in habits in relation to i) waste management, energy saving, and sustainable consumption, ii) mobility, iii) social inequalities, iv) generation of noise, v) utilization of natural spaces, and, vi) human population perception towards the future, and (2) the associations of these potential new habits with various socio-demographic variables. First, a SWOT analysis identified strengths (S), weaknesses (W), opportunities (O), and threats (T) generated by the pandemic lockdown measures. Second, a survey based on the aspects of the SWOT was administered among 2370 adults from 37 countries during the period from February to September 2021. We found that the short-term positive impacts on the natural environment were generally well recognized. In contrast, longer-term negative effects arise, but they were often not reported by the survey participants, such as greater production of plastic waste derived from health safety measures, and the increase in e-commerce use, which can displace small storefront businesses. We were able to capture a mismatch between perceptions and the reported data related to visits to natural areas, and generation of waste. We found that age and country of residence were major contributors in shaping the survey participants ´answers, which highlights the importance of government management strategies to address current and future environmental problems. Enhanced positive perceptions of the environment and ecosystems, combined with the understanding that livelihood sustainability, needs to be prioritized and would reinforce environmental protection policies to create greener cities. Moreover, new sustainable jobs in combination with more sustainable human habits represent an opportunity to reinforce environmental policy.

Methods for interpolating missing data in aerobiological databases.

Missing data is a common problem in scientific research. The availability of extensive environmental time series is usually laborious and difficult, and sometimes unexpected failures are not detected until samples are processed. Consequently, environmental databases frequently have some gaps with missing data in it. Applying an interpolation method before starting the data analysis can be a good solution in order to complete this missing information. Nevertheless, there are several different approaches whose accuracy should be considered and compared. In this study, data from 6 aerobiological sampling stations were used as an example of environmental data series to assess the accuracy of different interpolation methods. For that, observed daily pollen/spore concentration data series were randomly removed, interpolated by using different methods and then, compared with the observed data to measure the errors produced. Different periods, gap sizes, interpolation methods and bioaerosols were considered in order to check their influence in the interpolation accuracy. The moving mean interpolation method obtained the highest success rate as average. By using this method, a success rate of the 70% was obtained when the risk classes used in the alert systems of the pollen information platforms were taken into account. In general, errors were mostly greater when there were high oscillations in the concentrations of biotic particles during consecutive days. That is the reason why the pre-peak and peak periods showed the highest interpolation errors. The errors were also higher when gaps longer than 5 days were considered. So, for completing long periods of missing data, it would be advisable to test other methodological approaches. A new Variation Index based on the behaviour of the pollen/spore season (measurement of the variability of the concentrations every 2 consecutive days) was elaborated, which allows to estimate the potential error before the interpolation is applied.

Exploring the Western Mediterranean through X-chromosome.

In this study, we investigate the forensic and population genetics properties of 21 X-chromosome markers (9 X-Alu insertions and 12 X-STRs) in a dataset composed of 716 individuals from 11 Western Mediterranean populations. The high values of combined forensic parameters indicate that this 21 X-loci panel can complement autosomal or uniparental markers in kinship analysis and complex deficient paternity testing in the populations studied. Population analyses revealed a lower differentiation between Western Mediterranean human groups for X-STRs than for X-Alu insertion polymorphisms. Moreover, X-chromosome markers suggest a sex-biased migration rate, confirming the predominance of patrilocality in this area.

Middle eastern genetic legacy in the paternal and maternal gene pools of Chuetas.

Chuetas are a group of descendants of Majorcan Crypto-Jews (Balearic Islands, Spain) who were socially stigmatized and segregated by their Majorcan neighbours until recently; generating a community that, although after the seventeenth century no longer contained Judaic religious elements, maintained strong group cohesion, Jewishness consciousness, and endogamy. Collective memory fixed 15 surnames as a most important defining element of Chueta families. Previous studies demonstrated Chuetas were a differentiated population, with a considerable proportion of their original genetic make-up. Genetic data of Y-chromosome polymorphism and mtDNA control region showed, in Chuetas' paternal lineages, high prevalence of haplogroups J2-M172 (33%) and J1-M267 (18%). In maternal lineages, the Chuetas hallmark is the presence of a new sub-branching of the rare haplogroup R0a2m as their modal haplogroup (21%). Genetic diversity in both Y-chromosome and mtDNA indicates the Chueta community has managed to avoid the expected heterogeneity decrease in their gene pool after centuries of isolation and inbreeding. Moreover, the composition of their uniparentally transmitted lineages demonstrates a remarkable signature of Middle Eastern ancestry-despite some degree of host admixture-confirming Chuetas have retained over the centuries a considerable degree of ancestral genetic signature along with the cultural memory of their Jewish origin.

Predicting the start, peak and end of the Betula pollen season in Bavaria, Germany.

Betula pollen is frequently found in the atmosphere of central and northern Europe. Betula pollen are health relevant as they cause severe allergic reactions in the population. We developed models of thermal requirements to predict start, peak and end dates of the Betula main pollen season for Bavaria (Germany). Betula pollen data of one season from 19 locations were used to train the models. Estimated dates were compared with observed dates, and the errors were spatially represented. External validation was carried out with time series datasets of 3 different locations (36years in total). RESULTS: The temperature requirements to detonate the main pollen season proved non-linear. For the start date model (error of 8,75days during external validation), daily mean temperatures above a threshold of 10°C from 28th of February onwards were the most relevant. The peak model (error of 3.58days) takes into account mean daily temperatures accumulated since the first date of the main pollen season in which the daily average temperature exceeded 11°C. The end model (error of 3.75days) takes into account all temperatures accumulated since the start of the main pollen season. CONCLUSION: These models perform predictions that enable the allergic population to better manage their disease. With the established relationship between temperatures and pollen season dates, changes in the phenological behaviour of Betula species due to climate change can be also estimated in future studies by taking into account the different climate scenarios proposed by previous climate change studies.

Breast cancer PAM50 signature: correlation and concordance between RNA-Seq and digital multiplexed gene expression technologies in a triple negative breast cancer series.

BACKGROUND: Full RNA-Seq is a fundamental research tool for whole transcriptome analysis. However, it is too costly and time consuming to be used in routine clinical practice. We evaluated the transcript quantification agreement between RNA-Seq and a digital multiplexed gene expression platform, and the subtype call after running the PAM50 assay in a series of breast cancer patients classified as triple negative by IHC/FISH. The goal of this study is to analyze the concordance between both expression platforms overall, and for calling PAM50 triple negative breast cancer intrinsic subtypes in particular. RESULTS: The analyses were performed in paraffin-embedded tissues from 96 patients recruited in a multicenter, prospective, non-randomized neoadjuvant triple negative breast cancer trial (NCT01560663). Pre-treatment core biopsies were obtained following clinical practice guidelines and conserved as FFPE for further RNA extraction. PAM50 was performed on both digital multiplexed gene expression and RNA-Seq platforms. Subtype assignment was based on the nearest centroid classification following this procedure for both platforms and it was concordant on 96% of the cases (N = 96). In four cases, digital multiplexed gene expression analysis and RNA-Seq were discordant. The Spearman correlation to each of the centroids and the risk of recurrence were above 0.89 in both platforms while the agreement on Proliferation Score reached up to 0.97. In addition, 82% of the individual PAM50 genes showed a correlation coefficient > 0.80. CONCLUSIONS: In our analysis, the subtype calling in most of the samples was concordant in both platforms and the potential discordances had reduced clinical implications in terms of prognosis. If speed and cost are the main driving forces then the preferred technique is the digital multiplexed platform, while if whole genome patterns and subtype are the driving forces, then RNA-Seq is the preferred method.

Increasing resolution of airborne pollen forecasting at a discrete sampled area in the southwest Mediterranean Basin.

Daily fluctuations of the airborne pollen concentrations produce variations on symptomatology in allergic population. Such fluctuations are influenced by local vegetal coverage, flowering phenology, geography and climatology. Since 1991, airborne pollen of Malaga province (southern Spain) has been monitored in 7 different locations. Malaga station has been kept operational uninterruptedly throughout the studied period, while the rest of the stations only worked in periods of 2-4 years. Weekly, its pollen information is updated online to inform the population in order to prevent allergic diseases. Increasing the spatial resolution of pollen information would be very useful for allergic population living at unsampled locations. Due to the impossibility of keeping operational a high number of pollen stations covering the whole province of Malaga, the aim of this study is to create spatial models to extrapolate and forecast the pollen concentrations to Malaga province by using the concentrations registered at the capital as unique input. To do so, the relationships obtained between the airborne pollen concentrations detected at Malaga city and those detected at the other stations have been used to elaborate models for the main pollen types registered at the province. These models were spatially interpolated all over the province by using co-kriging techniques and the Compensated Thermicity Index as covariable. As result of this work, pollen distribution of the 8 most prevalent taxa has been depicted all over the whole Malaga province and an allergy alert system has been set up to extrapolate pollen information from Malaga to the whole province.

Analysis of 21 X-chromosome polymorphisms in urban and rural populations in Salta province (north-western Argentina).

Population genetic data for 21 X-chromosome markers (Alu insertions and STRs) are reported for two populations (rural and urban) in Salta province (north-western Argentina). New variants are described, confirming the complexity and variability of some markers in this set. Results reveal Salta populations harbor a high Native American component, despite their self-recognized European ancestry. Notwithstanding the high genetic similarity of both populations, the rural sample seems to have maintained a larger Amerindian legacy. Data further show these X-linked markers, especially STRs, are highly informative in Salta populations and, therefore, can contribute to the development of a local database for forensic purposes in north-western Argentina.

Genetic portrait of Jewish populations based on three sets of X-chromosome markers: Indels, Alu insertions and STRs.

Population genetic data for 53 X-chromosome markers (32 X-indels, 9 X-Alu insertions and 12 X-STRs) are reported for five populations with Jewish ancestry (Sephardim, North African Jews, Middle Eastern Jews, Ashkenazim, and Chuetas) and Majorca, as the host population of Chuetas. Genetic distances between these populations demonstrated significant differences, except between Sephardic and North African Jews, with the Chuetas as the most differentiated group, in accordance with the particular demographic history of this population. X-chromosome analysis and a comparison with autosomal data suggest a generally sex-biased demographic history in Jewish populations. Asymmetry was found between female and male effective population sizes both in the admixture processes between Jewish communities, and between them and their respective non-Jewish host populations. Results further show that these X-linked markers are highly informative for forensic purposes, and highlight the need for specific databases for differentiated Jewish populations.

Evolutionary history of Podarcis tiliguerta on Corsica and Sardinia.

BACKGROUND: Podarcis tiliguerta is a wall lizard endemic to the Mediterranean islands of Corsica and Sardinia. Previous findings of high mtDNA and morphological diversity have led to the suggestion that it may represent a species complex. Here, we analysed mitochondrial and nuclear markers (mtDNA, 3110 bp; 6 nDNA loci, 3961 bp) in P. tiliguerta sampled from thirty-two localities across Corsica and Sardinia. RESULTS: We find much greater intraspecific genetic divergence than between sister species of other Mediterranean island Podarcis, i.e., between P. lilfordi and P. pityusensis. We detected three mtDNA clusters in Corsica (North, South-East and South-West) and either two or three in Sardinia (North vs. South) depending on the clustering method. Only one or two nDNA groups were identified within each main island (again, depending on the method). A Bayesian time-calibrated multispecies coalescent tree was obtained from mtDNA and provided statistical support for a Miocene origin of the species (13.87 Ma, 95% HPD: 18.30-10.77 Ma). The posterior mean divergence time for the Corsican and Sardinian lineages was 12.75 Ma ago (95% HPD: 16.94-9.04 Ma). CONCLUSION: The results support the evolutionary distinctiveness of Corsican and Sardinian populations and also indicate a lack of post-divergence migration despite periods of contact being possible. Further to this, species delimitation analyses of Corsican and Sardinian lineages provided statistical support for their recognition as distinct (sister) taxa. Our results provide new insights into the biogeography of the Mediterranean biodiversity hotspot, and contribute important findings relevant to the systematics and evolution of this speciose lizard genus.

Prediction of non-muscle invasive bladder cancer outcomes assessed by innovative multimarker prognostic models.

BACKGROUND: We adapted Bayesian statistical learning strategies to the prognosis field to investigate if genome-wide common SNP improve the prediction ability of clinico-pathological prognosticators and applied it to non-muscle invasive bladder cancer (NMIBC) patients. METHODS: Adapted Bayesian sequential threshold models in combination with LASSO were applied to consider the time-to-event and the censoring nature of data. We studied 822 NMIBC patients followed-up >10 years. The study outcomes were time-to-first-recurrence and time-to-progression. The predictive ability of the models including up to 171,304 SNP and/or 6 clinico-pathological prognosticators was evaluated using AUC-ROC and determination coefficient. RESULTS: Clinico-pathological prognosticators explained a larger proportion of the time-to-first-recurrence (3.1 %) and time-to-progression (5.4 %) phenotypic variances than SNPs (1 and 0.01 %, respectively). Adding SNPs to the clinico-pathological-parameters model slightly improved the prediction of time-to-first-recurrence (up to 4 %). The prediction of time-to-progression using both clinico-pathological prognosticators and SNP did not improve. Heritability (h (2)) of both outcomes was <1 % in NMIBC. CONCLUSIONS: We adapted a Bayesian statistical learning method to deal with a large number of parameters in prognostic studies. Common SNPs showed a limited role in predicting NMIBC outcomes yielding a very low heritability for both outcomes. We report for the first time a heritability estimate for a disease outcome. Our method can be extended to other disease models.

Genetic diversity of 38 insertion-deletion polymorphisms in Jewish populations.

Population genetic data of 38 non-coding biallelic autosomal indels are reported for 466 individuals, representing six populations with Jewish ancestry (Ashkenazim, Mizrahim, Sephardim, North African, Chuetas and Bragança crypto-Jews). Intra-population diversity and forensic parameters values showed that this set of indels was highly informative for forensic applications in the Jewish populations studied. Genetic distance analysis demonstrated that this set of markers efficiently separates populations from different continents, but does not seem effective for molecular anthropology studies in Mediterranean region. Finally, it is important to highlight that although the genetic distances between Jewish populations were small, significant differences were observed for Chuetas and Bragança Jews, and therefore, specific databases must be used for these populations.

Genetic analysis of 12 X-chromosome STRs in Western Mediterranean populations.

Haplotype and allele frequencies of 12 X-STRs included in the Investigator Argus X-12 kit are reported for 255 individuals, representing four Western Mediterranean populations: Valencia (eastern mainland Spain) and the Balearic Islands (Majorca, Minorca, and Ibiza). Ibiza shows the lowest intra-population variability and the highest level of linkage disequilibrium together with an important genetic distance with regard to the geographically close populations, which is consistent with the historical evidence for long-term demographic isolation and its different matrilineal background.

New data on Perkinsus mediterraneus in the Balearic Archipelago: locations and affected species.

Perkinsus mediterraneus, a protozoan parasite that can cause perkinsosis (marine mollusc disease), was first detected in oysters Ostrea edulis from Mahon (Minorca, Balearic Islands, Spain) in 2004. Several years later it was also found in Andratx Harbour (Majorca, Balearic Islands) and in the Gulf of Manfredonia (Adriatic coast of Italy) in oyster populations. Since 2007, Perkinsus surveys have been conducted in different localities and shellfish species in the Balearic Archipelago. In the present work, we found P. mediterraneus in the Balearic Islands infecting oyster and other shellfish species. We describe infection with P. mediterraneus for the first time in Arca noae and Mimachlamys varia. The detection was carried out using Ray's fluid thioglycolate medium (RFTM), histology and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodologies. The internal transcribed spacer (ITS) region (including ITS1, 5.8S and ITS2) of P. mediterraneus ribosomal DNA was sequenced from infected bivalve gills (or from the body in Chamelea gallina) from Balearic Archipelago localities. Twelve haplotypes with a strong genetic similarity between them (97-100%) were observed in our samples. These data were completed with 12 more haplotypes from GenBank sequences. The phylogenetic relationship between Balearic P. mediterraneus haplotypes found in this study, those previously obtained in Mahon Harbour, and the Perkinsus spp. sequences available in GenBank clearly grouped the different Perkinsus spp. in distinct clades supported by strong bootstrap values. Moreover, these analyses detected different P. mediterraneus groups in O. edulis from Minorca Island. No abnormal mortalities or decline in populations were detected during the survey, except for C. gallina, which is also affected by Marteilia refringens.

Multilocus genetic diversity and historical biogeography of the endemic wall lizard from Ibiza and Formentera, Podarcis pityusensis (Squamata: Lacertidae).

Two monophyletic sister species of wall lizards inhabit the two main groups of Balearic Islands: Podarcis lilfordi from islets and small islands around Mallorca and Menorca and Podarcis pityusensis from Ibiza, Formentera and associated islets. Genetic diversity within the endangered P. lilfordi has been well characterized, but P. pityusensis has not been studied in depth. Here, 2430 bp of mtDNA and 15 microsatellite loci were analysed from P. pityusensis populations from across its natural range. Two main genetic groupings were identified, although geographical structuring differed slightly between the mtDNA and the nuclear loci. In general, individuals from islets/islands adjacent to the main island of Ibiza were genetically distinct from those from Formentera and the associated Freus islands for both mtDNA and the nuclear loci. However, most individuals from the island of Ibiza were grouped with neighbouring islets/islands for nuclear loci, but with Formentera and Freus islands for the mitochondrial locus. A time-calibrated Bayesian tree was constructed for the principal mitochondrial lineages within the Balearics, using the multispecies coalescent model, and provided statistical support for divergence of the two main P. pityusensis lineages 0.111-0.295 Ma. This suggests a mid-late Pleistocene intraspecific divergence, compared with an early Pleistocene divergence in P. lilfordi, and postdates some major increases in sea level between 0.4 and 0.6 Ma, which may have flooded Formentera. The program IMa2 provided a posterior divergence time of 0.089-0.221 Ma, which was similar to the multispecies coalescent tree estimate. More significantly, it indicated low but asymmetric effective gene copy migration rates, with higher migration from Formentera to Ibiza populations. Our findings suggest that much of the present-day diversity may have originated from a late Pleistocene colonization of one island group from the other, followed by allopatric divergence of these populations. Subsequent gene flow between these insular groups seems likely to be explained by recent human introductions. Two evolutionary significant units can be defined for P. pityusensis but these units would need to exclude the populations that have been the subjects of recent admixture.

Balearic archipelago: three islands, three beta-thalassemia population patterns.

The mutation spectrum of 175 ß-thalassemia (ß-thal) carriers, identified in pilot carrier screening on 22,713 individuals from Balearic Islands (Spain), is reported. The ß(0) CD39 (C>T) mutation is the most frequent (61.1%), followed by ß(+) IVS-I-110 (G>A) (12.0%), ß(+) IVS-I-6 (T>C) and ß(0) IVS-1-1 (G>A) (3.4% both) and eight other rare mutations (2.9-0.6%); with a distinct prevalence and distribution between islands. Minorca shows the highest prevalence in Iberian populations, with a single mutation, CD39 (C>T), present in most ß-thal carriers. Ibiza is the only Western Mediterranean population where the most frequent ß-thal mutation is IVS-I-110 (G>A). These results can be explained by a combination of historical-demographic characteristics together with evolutionary forces such as founder effect, genetic drift and probably selection by malaria. Knowledge of the mutational spectrum in the Balearic Islands will enable to optimize mutation detection strategy for genetic diagnosis of ß-thal in these islands.

Pain sensitivity in fibromyalgia is associated with catechol-O-methyltransferase (COMT) gene.

BACKGROUND: Recent evidence suggests that genetic factors might contribute to individual differences in pain sensitivity, risk for developing clinical pain conditions and efficacy of pain treatments. The purpose of the present study was to investigate the relationship of three common haplotypes of COMT gene affecting the metabolism of catecholamines on pain sensitivity in patients with fibromyalgia (FM). METHODS: One hundred and thirteen FM patients and 65 age-matched healthy volunteers participated in the study. We genotyped four single-nucleotide polymorphisms (SNPs) (rs6269, rs4633, rs4818 and rs4680 or Val158Met) and identified haplotypes previously designated as low (LPS), average (APS) and high pain sensitivity (HPS). Thermal, pressure and touch thresholds were also examined using a quantitative sensory testing protocol. RESULTS: The frequency of genetic variations associated with low COMT enzyme activity was significantly higher in FM patients than in healthy volunteers. FM patients were more sensitive to experimental pain than healthy volunteers and, in particular, FM individuals with the met/met genotype (Val158Met SNP) or the HPS-APS haplotypes showing higher sensitivity to thermal and pressure pain stimuli than patients carrying the LPS haplotype or val alleles (Val158Met SNP). No differences due to genotype or haplotypes were found on non-painful touch thresholds. CONCLUSIONS: According with previous research, our findings revealed that haplotypes of the COMT gene and genotypes of the Val158Met polymorphism play a key role on pain sensitivity in FM patients.

Allele frequencies of 15 STRs in the Calchaqui Valleys population (North-Western Argentina).

Allele frequencies for 15 short tandem repeat (STR) loci were obtained from a sample of 110 individuals from the Calchaqui Valleys population (North-Western Argentina). The combined power of exclusion and combined power of discriminating for the 15 tested STR loci were 0.999964 and 0.9999999999999998, respectively. Matching probability was 1 in 4.58 × 10(15). Therefore, it may be concluded that the set of 15 STRs included in the AmpF STR Identifiler kit, represents a powerful tool for forensic applications, paternity testing and population genetics studies in the Calchaqui Valleys population.