| 1. |
- Borssén, Magnus, et al.
(author)
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DNA methylation holds prognostic information in relapsed precursor B-cell acute lymphoblastic leukemia
- 2018
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In: Clinical Epigenetics. - : BIOMED CENTRAL LTD. - 1868-7083 .- 1868-7075. ; 10
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Journal article (peer-reviewed)abstract
- Background: Few biological markers are associated with survival after relapse of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In pediatric T-cell ALL, we have identified promoter-associated methylation alterations that correlate with prognosis. Here, the prognostic relevance of CpG island methylation phenotype (CIMP) classification was investigated in pediatric BCP-ALL patients.Methods: Six hundred and one BCP-ALL samples from Nordic pediatric patients (age 1-18) were CIMP classified at initial diagnosis and analyzed in relation to clinical data.Results: Among the 137 patients that later relapsed, patients with a CIMP-profile (n = 42) at initial diagnosis had an inferior overall survival (pOS(5years) 33%) compared to CIMP+ patients (n = 95, pOS(5years) 65%) (p = 0.001), which remained significant in a Cox proportional hazards model including previously defined risk factors.Conclusion: CIMP classification is a strong candidate for improved risk stratification of relapsed BCP-ALL.
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| 2. |
- Dublinowska, M., et al.
(author)
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Intersexuality in the Blue Mussel Mytilus edulis Complex (Mytilidae) from the Baltic Sea and the Danish Strait
- 2016
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In: American Malacological Bulletin. - : American Malacological Society. - 0740-2783 .- 2162-2698. ; 34:1, s. 28-39
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Journal article (peer-reviewed)abstract
- Populations of Mytilus edulis complex were studied from 13 stations located at three areas of the Baltic Sea (the Gulf of Gdańsk, Poland; Tvärminne area, Finland; Trosa Archipelago, Sweden) and the Skagerrak sound (Kristineberg, Sweden). The main purpose of the study was to document the occurrence of intersexuality along longitudinal salinity change using squash and histology for comparative reasons. Intersex was identified in all four geographical areas at an average frequency of 1.8%. Squash technique revealed the highest intersex frequency in the Gulf of Gdańsk (up to 6.25%) whereas histology examination did so in the Kristineberg area (up to 10%). In the Tvärminne area and in the Trosa Archipelago the average frequency of intersex did not exceed 2% regardless of the technique used; this suggests a natural induction of the phenomenon. Statistically significant spatial differences in intersex frequency were confirmed for mussels inhabiting polluted hotspots in the Gulf of Gdańsk and at the west coast of Sweden (Kristineberg). Therefore, for these localities artificial induction of intersexuality as a consequence of adverse environmental threats (pollution, parasite outbreaks) is further suggested. Furthermore, squash technique - being less sensitive in identifying intersex when compared to histology - is not recommended for mussels with severe reproductive impairments making a proper analysis of gonads impossible. Intersexual individuals were also characterized by less developed gonads and lower gonado-somatic index (GSI) than males and females. Significantly lower GSI revealed less energy allocation towards reproduction in populations from the Trosa Archipelago and Tvärminne area in comparison to those from the Gulf of Gdańsk and from Kristineberg.
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| 3. |
- Jahnke, Marlene, et al.
(author)
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Population genetic structure and connectivity of the seagrass Thalassia hemprichii in the Western Indian Ocean is influenced by predominant ocean currents
- 2019
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In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 9:16, s. 8953-8964
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Journal article (peer-reviewed)abstract
- This study is the first large-scale genetic population study of a widespread climax species of seagrass, Thalassia hemprichii, in the Western Indian Ocean (WIO). The aim was to understand genetic population structure and connectivity of T. hemprichii in relation to hydrodynamic features. We genotyped 205 individual seagrass shoots from 11 sites across the WIO, spanning over a distance of similar to 2,700 km, with twelve microsatellite markers. Seagrass shoots were sampled in Kenya, Tanzania (mainland and Zanzibar), Mozambique, and Madagascar: 4-26 degrees S and 33-48 degrees E. We assessed clonality and visualized genetic diversity and genetic population differentiation. We used Bayesian clustering approaches (TESS) to trace spatial ancestry of populations and used directional migration rates (DivMigrate) to identify sources of gene flow. We identified four genetically differentiated groups: (a) samples from the Zanzibar channel; (b) Mozambique; (c) Madagascar; and (d) the east coast of Zanzibar and Kenya. Significant pairwise population genetic differentiation was found among many sites. Isolation by distance was detected for the estimated magnitude of divergence (D-EST), but the three predominant ocean current systems (i.e., East African Coastal Current, North East Madagascar Current, and the South Equatorial Current) also determine genetic connectivity and genetic structure. Directional migration rates indicate that Madagascar acts as an important source population. Overall, clonality was moderate to high with large differences among sampling sites, indicating relatively low, but spatially variable sexual reproduction rates. The strongest genetic break was identified for three sites in the Zanzibar channel. Although isolation by distance is present, this study suggests that the three regionally predominant ocean current systems (i.e., East African Coastal Current, North East Madagascar Current, and the South Equatorial Current) rather than distance determine genetic connectivity and structure of T. hemprichii in the WIO. If the goal is to maintain genetic connectivity of T. hemprichii within the WIO, conservation planning and implementation of marine protection should be considered at the regional scale-across national borders.
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| 4. |
- Larsson, Josefine
(author)
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Genetic Aspects of Environmental Disturbances in Marine Ecosystems : Studies of the Blue Mussel in the Baltic Sea
- 2017
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Doctoral thesis (other academic/artistic)abstract
- Anthropogenic environmental changes can serve as drivers for evolutionary responses in wild populations. To predict the long-term impact of anthropogenic changes on populations, it is crucial to understand the genetic effects caused by these disturbances. The Baltic Sea is considered to be one of the world’s most contaminated seas, and the increase of anthropogenic chemical pollution is a major threat to its ecosystems. This thesis assesses the impact of harbors and sewage treatment plants on physiological traits and genetic structure of resident populations of blue mussels at replicated sites in the Baltic Sea. The initial evaluation of the overall genetic pattern in blue mussel populations in the Swedish West Coast, the Baltic Proper and the Bothnian Sea found genetic differentiation between the three water basins and a low genetic differentiation within each basin, especially within the Baltic Proper. Despite the low genetic differentiation among blue mussels within the Baltic Proper, a parallel genetic differentiation associated with sewage treatment plant effluents was found in this basin. This included genomic regions with a high degree of differentiation between reference sites and sites affected by sewage plants effluent. This genetic differentiation is suggested to be due to post-dispersal selection acting in each generation. In contrast, no parallel genetic differentiation was associated with harbors. We identified five genomic regions in blue mussels, showing strong signs of selection, shared among three out of four replicated reference sites and sites affected by sewage effluents in the Baltic Proper i.e. Askö, Tvärminne and Karlskrona. An initial characterization of these genomic regions revealed functions related to immune and endocrine responses, oxidative stress and shell formation. Our results indicate that selection caused by sewage effluents involves multiple loci. The same genomic regions are found across different locations in the Baltic Proper but there are also unique genomic regions at each location. No genotoxic or histopathological effects were found among blue mussels from sewage effluent-affected areas but a higher frequency of histological abnormalities in the digestive gland were observed in mussels from harbors.
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| 5. |
- Larsson, Josefine, et al.
(author)
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Multi biomarker analysis of pollution effect on resident populations of blue mussels from the Baltic Sea
- 2018
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In: Aquatic Toxicology. - : Elsevier. - 0166-445X .- 1879-1514. ; 198, s. 240-256
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Journal article (peer-reviewed)abstract
- Anthropogenic pollution including metals, petroleum, toxins, nutrients and many others is a growing problem in the marine environment. These are important factors altering the environment and by that the fate of many local populations of marine organisms. The aim of this study was to assess the impact of selected point pollution sources on resident populations of the blue mussel (Mytilus edulis trossulus) in the Baltic Sea using multiple biomarker approach. The study used a nested sampling scheme in which sites from reference (REF) habitats are geographically paired with selected sites from sewage treatment plants (STP) and harbors (HAR). The results showed that mussels from harbors had a higher frequency of histological abnormalities in the digestive gland compared to mussels from sewage effluent affected areas and reference sites. However these mussels together with mussels from STPs had higher lipid content, body mass index (BMI) and gonado-somatic index (GSI) compared to mussels from reference sites. A marked spatial variability was found with a stronger toxicity of ambient environment affecting resident mussel populations in the Gulf of Gdańsk area, while an opposite pattern was found in Tvärminne area. Yet the blue mussels sampled in the Gulf of Gdańsk were characterized by the highest GSI and BMI values compared to Askö and Tvärminne populations. No differences in analyzed biomarker response related to species identity, measured by a species-specific genetic marker, were found indicative of strong genetic introgression in the Baltic Proper.
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| 6. |
- Larsson, Josefine, et al.
(author)
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Regional genetic differentiation in the blue mussel from the Baltic Sea area
- 2017
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In: Estuarine, Coastal and Shelf Science. - : Academic Press. - 0272-7714 .- 1096-0015. ; , s. 98-109
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Journal article (peer-reviewed)abstract
- Connectivity plays an important role in shaping the genetic structure and in evolution of local adaptation. In the marine environment barriers to gene flow are in most cases caused by gradients in environmental factors, ocean circulation and/or larval behavior. Despite the long pelagic larval stages, with high potential for dispersal many marine organisms have been shown to have a fine scale genetic structuring. In this study, by using a combination of high-resolution genetic markers, species hybridization data and biophysical modeling we can present a comprehensive picture of the evolutionary landscape for a keystone species in the Baltic Sea, the blue mussel. We identified distinct genetic differentiation between the West Coast, Baltic Proper and Bothnian Sea regions, with lower gene diversity in the Bothnian Sea. Oceanographic connectivity together with salinity and to some extent species identity provides explanations for the genetic differentiation between the West Coast and the Baltic Sea (Baltic Proper and Bothnian Sea). The genetic differentiation between the Baltic Proper and Bothnian Sea cannot be directly explained by oceanographic connectivity, species identity or salinity, while the lower connectivity to the Bothnian Sea may explain the lower gene diversity. © 2016.
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| 7. |
- Larsson, Josefine, et al.
(author)
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Sewage treatment plant associated genetic differentiation in the blue mussel from the Baltic Sea and Swedish west coast
- 2016
-
In: PeerJ. - : PeerJ. - 2167-8359. ; 4
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Journal article (peer-reviewed)abstract
- Human-derived environmental pollutants and nutrients that reach the aquatic environment through sewage effluents, agricultural and industrial processes are constantly contributing to environmental changes that serve as drivers for adaptive responses and evolutionary changes in many taxa. In this study, we examined how two types of point sources of aquatic environmental pollution, harbors and sewage treatment plants, affect gene diversity and genetic differentiation in the blue mussel in the Baltic Sea area and off the Swedish west coast (Skagerrak). Reference sites (REF) were geographically paired with sites from sewage treatments plant (STP) and harbors (HAR) with a nested sampling scheme, and genetic differentiation was evaluated using a high-resolution marker amplified fragment length polymorphism (AFLP). This study showed that genetic composition in the Baltic Sea blue mussel was associated with exposure to sewage treatment plant effluents. In addition, mussel populations from harbors were genetically divergent, in contrast to the sewage treatment plant populations, suggesting that there is an effect of pollution from harbors but that the direction is divergent and site specific, while the pollution effect from sewage treatment plants on the genetic composition of blue mussel populations acts in the same direction in the investigated sites.
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| 8. |
- Leion, Felicia, et al.
(author)
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Estimating glomerular filtration rate (GFR) in children. The average between a cystatin C- and a creatinine-based equation improves estimation of GFR in both children and adults and enables diagnosing Shrunken Pore Syndrome.
- 2017
-
In: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 77:5, s. 338-344
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Journal article (peer-reviewed)abstract
- Estimating glomerular filtration rate (GFR) in adults by using the average of values obtained by a cystatin C- (eGFRcystatin C) and a creatinine-based (eGFRcreatinine) equation shows at least the same diagnostic performance as GFR estimates obtained by equations using only one of these analytes or by complex equations using both analytes. Comparison of eGFRcystatin C and eGFRcreatinine plays a pivotal role in the diagnosis of Shrunken Pore Syndrome, where low eGFRcystatin C compared to eGFRcreatinine has been associated with higher mortality in adults. The present study was undertaken to elucidate if this concept can also be applied in children. Using iohexol and inulin clearance as gold standard in 702 children, we studied the diagnostic performance of 10 creatinine-based, 5 cystatin C-based and 3 combined cystatin C-creatinine eGFR equations and compared them to the result of the average of 9 pairs of a eGFRcystatin C and a eGFRcreatinine estimate. While creatinine-based GFR estimations are unsuitable in children unless calibrated in a pediatric or mixed pediatric-adult population, cystatin C-based estimations in general performed well in children. The average of a suitable creatinine-based and a cystatin C-based equation generally displayed a better diagnostic performance than estimates obtained by equations using only one of these analytes or by complex equations using both analytes. Comparing eGFRcystatin and eGFRcreatinine may help identify pediatric patients with Shrunken Pore Syndrome.
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| 9. |
- Lindqvist, C Mårten, et al.
(author)
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The Mutational Landscape in Pediatric Acute Lymphoblastic Leukemia Deciphered by Whole Genome Sequencing
- 2015
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In: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 36:1, s. 118-128
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Journal article (peer-reviewed)abstract
- Genomic characterization of pediatric acute lymphoblastic leukemia (ALL) has identified distinct patterns of genes and pathways altered in patients with well-defined genetic aberrations. To extend the spectrum of known somatic variants in ALL, we performed whole genome and transcriptome sequencing of three B-cell precursor patients, of which one carried the t(12;21)ETV6-RUNX1 translocation and two lacked a known primary genetic aberration, and one T-ALL patient. We found that each patient had a unique genome, with a combination of well-known and previously undetected genomic aberrations. By targeted sequencing in 168 patients, we identified KMT2D and KIF1B as novel putative driver genes. We also identified a putative regulatory non-coding variant that coincided with overexpression of the growth factor MDK. Our results contribute to an increased understanding of the biological mechanisms that lead to ALL and suggest that regulatory variants may be more important for cancer development than recognized to date. The heterogeneity of the genetic aberrations in ALL renders whole genome sequencing particularly well suited for analysis of somatic variants in both research and diagnostic applications.
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| 10. |
- Nordlund, Jessica, et al.
(author)
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DNA methylation-based subtype prediction for pediatric acute lymphoblastic leukemia
- 2015
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In: Clinical Epigenetics. - : Springer Science and Business Media LLC. - 1868-7083 .- 1868-7075. ; 7
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Journal article (peer-reviewed)abstract
- Background: We present a method that utilizes DNA methylation profiling for prediction of the cytogenetic subtypes of acute lymphoblastic leukemia (ALL) cells from pediatric ALL patients. The primary aim of our study was to improve risk stratification of ALL patients into treatment groups using DNA methylation as a complement to current diagnostic methods. A secondary aim was to gain insight into the functional role of DNA methylation in ALL. Results: We used the methylation status of similar to 450,000 CpG sites in 546 well-characterized patients with T-ALL or seven recurrent B-cell precursor ALL subtypes to design and validate sensitive and accurate DNA methylation classifiers. After repeated cross-validation, a final classifier was derived that consisted of only 246 CpG sites. The mean sensitivity and specificity of the classifier across the known subtypes was 0.90 and 0.99, respectively. We then used DNA methylation classification to screen for subtype membership of 210 patients with undefined karyotype (normal or no result) or non-recurrent cytogenetic aberrations('other' subtype). Nearly half (n = 106) of the patients lacking cytogenetic subgrouping displayed highly similar methylation profiles as the patients in the known recurrent groups. We verified the subtype of 20% of the newly classified patients by examination of diagnostic karyotypes, array-based copy number analysis, and detection of fusion genes by quantitative polymerase chain reaction (PCR) and RNA-sequencing (RNA-seq). Using RNA-seq data from ALL patients where cytogenetic subtype and DNA methylation classification did not agree, we discovered several novel fusion genes involving ETV6, RUNX1, and PAX5. Conclusions: Our findings indicate that DNA methylation profiling contributes to the clarification of the heterogeneity in cytogenetically undefined ALL patient groups and could be implemented as a complementary method for diagnosis of ALL. The results of our study provide clues to the origin and development of leukemic transformation. The methylation status of the CpG sites constituting the classifiers also highlight relevant biological characteristics in otherwise unclassified ALL patients.
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| 11. |
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| 12. |
- Palmqvist, Hanna, et al.
(author)
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Fathers' and co-mothers' voices about breastfeeding and equality - A Swedish perspective
- 2015
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In: Women and Birth. - : Elsevier BV. - 1871-5192 .- 1878-1799. ; 28:3, s. E63-E69
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Journal article (peer-reviewed)abstract
- Background: Breastfeeding has benefits for mother and child and the partner's support influences the decision as well as the duration of breastfeeding. The aim of this study was to describe partners' knowledge and feelings regarding breastfeeding and how they reason about equality and involvement during the lactation period. Methods: A qualitative study using semi-structured interviews with 7 male and 2 female partners (labelled co-mothers) of breastfeeding mothers. The interviews were transcribed and analysed using a phenomenological approach. Results: The main theme Wish for the child to be breastfed/get breast milk described the informants' desire that their child was breastfed and this desire was based on knowledge of benefits of breastfeeding but also on intuitive feelings of breastfeeding as something natural. The main theme Effect of breastfeeding on fathers/co-mothers described how breastfeeding affected the informants and their relationship to the child and the mother in different ways. The main theme Adaptation and acceptance described how informants accepted the impact that breastfeeding had and/or adapted to it and continued to wish for the child to receive breast milk. Conclusion: The informants desired that their children be breastfed/get breast milk. Breastfeeding affected the informants in different ways, which they handled by adapting to and accepting the situation, and they expressed a continued desire that their children be breastfed/get breast milk. Parental classes should include both parents to be and address how breastfeeding can be successfully performed and supported without threatening the equality between the parents.
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| 13. |
- Porseryd, Tove, et al.
(author)
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Altered non-reproductive behavior and feminization caused by developmental exposure to 17α-ethinylestradiol persist to adulthood in three-spined stickleback (Gasterosteus aculeatus)
- 2019
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In: Aquatic Toxicology. - : Elsevier. - 0166-445X .- 1879-1514. ; 207, s. 142-152
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Journal article (peer-reviewed)abstract
- The synthetic estrogen 17α-ethinylestradiol (EE2), ubiquitous in the aquatic environment and commonly detected in sewage effluents, interferes with the endocrine system in multiple ways. Exposure during sensitive windows of development causes persistent effects on fertility, reproductive and non-reproductive behavior in mammals and fish. In the present study, three-spined stickleback (Gasterosteus aculeatus) were exposed to nominal 0 and 20 ng/L EE2 from fertilization to 7 weeks post-hatch. After 8 months of remediation in clean water three non-reproductive behaviors, not previously analyzed in developmentally EE2-exposed progeny of wild-caught fish, were evaluated. Chemical analysis revealed that the nominal 0 and 20 ng/L exposure contained 5 and 30 ng/L EE2, respectively. Therefore, the use of control fish from previous experiments was necessary for comparisons. Fish exposed during development showed significant concentration-dependent reduction in anxiety-like behavior in the scototaxis (light/dark preference) test by means of shorter latency to first entrance to the white compartment, more visits in white, and longer total time in white compared to unexposed fish. In the novel tank test, developmental exposure significantly increased the number of transitions to the upper half of the aquaria. Exposure to EE2 during development did not alter shoal cohesion in the shoaling test compared with unexposed fish but fish exposed to 30 ng/L EE2 had significantly longer latency to leave the shoal and fewer transitions away from the shoal compared to fish exposed to 5 ng/L EE2. Skewed sex ratio with more females, sex reversal in genetic males as well as intersex in males was observed after exposure to 30, but not 5 ng/L EE2. In conclusion, EE2 exposure during development in three-spined stickleback resulted in persistent effects on anxiety-like behaviors. These long-term effects from developmental exposure are likely to be of higher relevance for natural populations than are short-term effects from adult exposure.
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| 14. |
- Åhsberg, Josefine, et al.
(author)
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Ebf1 heterozygosity results in increased DNA damage in pro-B cells and their synergistic transformation by Pax5 haploinsufficiency
- 2015
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 125:26, s. 4052-4059
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Journal article (peer-reviewed)abstract
- Early B-cell factor 1 (Ebf1) is a transcription factor with documented dose-dependent functions in normal and malignant B-lymphocyte development. To understand more about the roles of Ebf1 in malignant transformation, we investigated the impact of reduced functional Ebf1 dosage on mouse B-cell progenitors. Gene expression analysis suggested that Ebf1 was involved in the regulation of genes important for DNA repair and cell survival. Investigation of the DNA damage in steady state, as well as after induction of DNA damage by UV light, confirmed that pro-B cells lacking 1 functional allele of Ebf1 display signs of increased DNA damage. This correlated to reduced expression of DNA repair genes including Rad51, and chromatin immunoprecipitation data suggested that Rad51 is a direct target for Ebf1. Although reduced dosage of Ebf1 did not significantly increase tumor formation in mice, a dramatic increase in the frequency of pro-B cell leukemia was observed in mice with combined heterozygous mutations in the Ebf1 and Pax5 genes, revealing a synergistic effect of combined dose reduction of these proteins. Our data suggest that Ebf1 controls DNA repair in a dose-dependent manner providing a possible explanation to the frequent involvement of EBF1 gene loss in human leukemia.
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