| 1. |
- Winberg, Johanna, et al.
(författare)
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Chimerism Resulting From Parthenogenetic Activation and Dispermic Fertilization
- 2010
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Ingår i: American Journal of Medical Genetics, Part A. - : Wiley. - 1552-4825 .- 1552-4833. ; 152A:9, s. 2277-2286
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Tidskriftsartikel (refereegranskat)abstract
- Whole-body human chimerism is the result of two zygotes giving rise to one individual, and is a rarely detected condition. We have studied the molecular background and discuss the likely mechanism for the chimerism in a patient with a 46,XX/47,XY,+14 karyotype and ambiguous genitalia, cryptorchidism, pigment anomalies, and normal psychomotor development. We have used karyotyping, interphase-FISH and array-CGH analysis as well as molecular analysis of polymorphic markers from 48 loci in order to define the origin and percentage of 47,XY,+14 cells in different tissues. Based on the findings of two paternal alleles and the detection of homozygous maternal alleles without evidence of crossing-over, and the fact that four alleles were never detected, our results indicate that the chimerism in our patient is the result of dispermic fertilization of a parthenogenetically activated oocyte. Our report underlines that cytogenetic findings suggesting mosaicism might actually indicate chimerism as an underlying mechanism in patients. It also highlights the difficulties in predicting the clinical outcome in patients with genetic aberrations in mosaic or chimeric form.
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| 2. |
- Axling, Johanna, 1986-, et al.
(författare)
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Boldness, activity, and aggression : Insights from a large-scale study in Baltic salmon (Salmo salar L)
- 2023
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:7
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Tidskriftsartikel (refereegranskat)abstract
- Atlantic salmon (Salmo salar) display high levels of agonistic behavior in aquaculture farms, resulting in fin damage and chronic stress. Aggression affects fish growth and performance negatively and presents a serious welfare problem. Indeed, it would be beneficial to identify, separate or exclude overly aggressive individuals. Research on behavioral syndromes suggests that aggressive behavior may correlate with traits from other contexts, such as boldness and locomotory activity. We aimed to develop a high-throughput method to quantify and predict aggressive behavior of individual parr in hatchery-reared Baltic salmon (Salmo salar L.). We screened approximately 2000 parr in open field (OF) and mirror image stimulation (MIS) tests. We extracted seven variables from video tracking software for each minute of the tests; distance moved and duration moving (activity), the duration in and number of entries to the center of the arena (boldness), the distance moved in, and duration spent in the area adjacent to the mirror during the MIS test (aggressiveness) and head direction (lateralization). To investigate the relationship between activity, boldness, and aggression we first correlated the first six variables to one another. Second, we assigned individuals to high, medium, low or zero aggression groups based on the MIS test and quantified activity and boldness in each group. Third, we analyzed whether the fish viewed the mirror with the left or right eye. Our results show that medium and low aggressive fish were the most active, while highly aggressive fish showed average activity. Aggressive groups did not differ in boldness. Activity and boldness were positively correlated. Finally, we detected a preference for fish to view the mirror with the left eye. We conclude that although the OF may not accurately predict aggressive behavior, the MIS test can be used for large-scale aggression profiling of juvenile salmon
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| 3. |
- Axling, Johanna, et al.
(författare)
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Boldness in Zebrafish Larvae-Development and Differences between a Domesticated Lab Strain and Offspring of Wild-Caught Fish
- 2022
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Ingår i: Fishes. - : MDPI AG. - 2410-3888. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- Zebrafish (Danio rerio) are becoming one of the most important model organisms in behavioural neuroscience. It has been shown repeatedly that different zebrafish strains show large behavioural differences. These divergent behavioural profiles may have a genetic basis, but environmental factors and previous experience are also known to greatly affect the behavioural phenotype of zebrafish. It could be expected that behavioural differences at the larval stage should be less affected by environmental factors and experience. In the present study, we screened larvae of zebrafish of the AB strain and offspring of wild-caught zebrafish for boldness, using an open field test. In order to follow the behavioural development, we studied larvae at the age of 5-, 7-, 12- and 30-days post fertilization (dpf). Behaviour, as well as behavioural development, clearly differed between the larvae of the different strains. Wild larvae showed larger total distance moved than AB larvae, both at light and dark conditions. These differences were already present at 12 dpf but became more pronounced with age. Wild larvae had a greater variance compared to AB larvae for most of the variables. We have previously shown that bold and shy adult zebrafish differ in the brain expression of dopamine and opioid receptors. The results of the current study show that wild larvae display significantly higher brain expression of drd2b than AB larvae at 30 dpf, a difference that could be related to differences in activity. We did not detect any differences in the expression of opioid receptors.
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| 4. |
- Axling, Johanna
(författare)
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Intraspecific divergence and phenotypic plasticity in behavioural profiles of teleost fish
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Behavioural differences between and within individuals can greatly affect the outcome of behavioural studies. In addition, behavioural interactions between individuals can compromise the health and welfare of captive fish. In paper I, I investigate the relationship between locomotory activity, boldness and aggressive behaviour in ~2000 hatchery-reared Baltic salmon parr (Salmo salar L), with the aim to predict aggression level from activity and boldness displayed in the open field test. We found that activity and boldness were positively correlated while they were not correlated with aggression level measured in the mirror stimulation test. Surprisingly, medium and low aggressive fish were the most active, while highly aggressive fish showed only average activity. We conclude that the open field test, although efficient, does not accurately predict aggressive behaviour. However, the mirror stimulation test can be used for high-throughput aggression profiling of juvenile salmon. In paper II, I tested a subset of the salmon parr for a second time, to quantify behavioural consistency between trials and to investigate if phenotypic plasticity was related to aggression level. Our results show that activity was the most stable behavioural variable between trials. Even though aggression was not consistent between tests, we found that the fish displaying a low level of aggression in the first test were less consistent in their behaviour than highly aggressive fish. In paper III, we compared the behavioural development of zebrafish larvae of two strains, the AB strain and 5th generation offspring of wild-caught zebrafish from India. Individual larvae were screened for activity and boldness at the age of 5-, 7-, 12- and 30-days post fertilization using an open field test with alternating light and dark cycles. Furthermore, we analysed mRNA expression of genes encoding serotonin, dopamine, galanin and opioid receptor subunits, as well the peptide neurotransmitter spexin in whole brain samples from juveniles, with the aim to investigate potential neuroendocrine mechanisms of divergent behavioural profiles. Our results show that larvae from the wild strain had higher activity and greater variance in their behaviour than AB larvae, under both light and dark conditions. Wild larvae also had significantly higher expression of dopamine receptor subunit drd2b at 30 days post fertilization, a difference that could be related to difference in activity. In conclusion, the results presented in this thesis contribute to our understanding of animal behavioural profiles, at both an intraspecific and intraindividual level.
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| 5. |
- Axling, Johanna, et al.
(författare)
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Locomotory activity is more consistent over trials than thigmotaxis and aggressive behaviour in sea-ranched Baltic salmon (Salmo salar L.)
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In the current study we examined the behavioural consistency over time of activity, boldness and aggressive behaviour in Baltic salmon (Salmo salar L) parr. We performed a combined open field and mirror stimulation test on two test occasions, recording three behavioural variables: duration moving in the whole arena (activity), duration in centre zone (boldness) and distance between nose and mirror (aggression) during the mirror stimulation test. Of these behavioural variables activity proved the most consistent between trials. Moreover, the fish that displayed least aggressive behaviour in the first trial had the largest variance in their behavioural variables compared to highly aggressive fish, which showed more consistent levels of the behavioural variables. Overall, aggression level in the first test was a strong predictor of the other behavioural variables, in addition to significant effects of water temperature and body weight. In conclusion, our results show that juvenile Baltic salmon classified according to aggression level during the first test also differ in other aspects of their behavioural profile, and highly aggressive salmon are less phenotypically plastic compared to low aggressive fish.
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| 6. |
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| 7. |
- Lindstrand, Anna, et al.
(författare)
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Genome sequencing is a sensitive first-line test to diagnose individuals with intellectual disability
- 2022
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Ingår i: Genetics in Medicine. - : ELSEVIER SCIENCE INC. - 1098-3600 .- 1530-0366. ; 24:11, s. 2296-2307
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Individuals with intellectual disability (ID) and/or neurodevelopment disorders (NDDs) are currently investigated with several different approaches in clinical genetic diagnostics. Methods: We compared the results from 3 diagnostic pipelines in patients with ID/NDD: genome sequencing (GS) first (N = 100), GS as a secondary test (N = 129), or chromosomal microarray (CMA) with or without FMR1 analysis (N = 421). Results: The diagnostic yield was 35% (GS -first), 26% (GS as a secondary test), and 11% (CMA/FMR1). Notably, the age of diagnosis was delayed by 1 year when GS was performed as a secondary test and the cost per diagnosed individual was 36% lower with GS first than with CMA/FMR1. Furthermore, 91% of those with a negative result after CMA/FMR1 analysis (338 individuals) have not yet been referred for additional genetic testing and remain undiagnosed. Conclusion: Our findings strongly suggest that genome analysis outperforms other testing strategies and should replace traditional CMA and FMR1 analysis as a first-line genetic test in individuals with ID/NDD. GS is a sensitive, time-and cost-effective method that results in a confirmed molecular diagnosis in 35% of all referred patients. (c) 2022 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 8. |
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| 9. |
- Ulvros, Eva Helen, et al.
(författare)
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Riddarhusbalerna
- 2013
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Ingår i: Adeln och dess hus. - 9515507855 ; , s. 179-200
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Bokkapitel (populärvet., debatt m.m.)abstract
- Lantdags- och Riddarhusbaler i Finland under 1800- och 1900-tal. Dans och sällskapsliv. Nöjeskultur i Finland i societeten under 1800- och 1900-tal.
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| 10. |
- Winberg, Johanna
(författare)
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Clinical and molecular genetic characterization of congenital malformations
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Congenital malformations are important causes of perinatal mortality and morbidity, and around 4% of children are diagnosed with a malformation during their first year of life. Despite improved surgical treatment, several malformations are associated with lifelong sequelae requiring specialized health care. Important issues for these families are the etiology, prognosis and recurrence risk of the malformation in future pregnancies. Nowadays, around 50% of patients with malformations in combination with cognitive impairment receive an etiologic diagnosis after genetic evaluation. The aims of this thesis were to increase the knowledge of genetic causes behind congenital malformations, to improve clinical genetic investigations of these patients and at the same time to identify genes involved in normal and impaired organ development. Study I Whole-body human chimerism is the result of two zygotes giving rise to one individual, and is a rarely detected condition that can cause congenital anomalies. We have studied the molecular background of a 46,XX/47,XY,+14 karyotype identified in clinical genetic investigation in a boy with disorder of sex development (DSD). Based on molecular findings, we suggest that the chimerism in our patient is the result of dispermic fertilization of a parthenogenetically activated oocyte. This study highlights chimerism as an underlying cause of distinct cell populations in an individual, and shows the difficulty of predicting the severity of associated phenotypes in mosaic or chimeric forms of genetic aberrations. Study II Tetrasomy 14 is a rare condition associated with multiple malformations, cognitive impairment and mortality when present in non-mosaic form. We report on molecular genetic and mitochondrial studies in an 8-year-old girl with a marker chromosome 14. We showed that the marker chromosome originated from maternal meiosis and was present in all cells analyzed, providing evidence that survival beyond infancy is possible in non-mosaic forms of this condition. The results emphasize importance of updating existing data on clinical outcomes of patients with severe diseases to correspond to high standard pediatric care. Study III VACTERL association is a condition with multiple malformations including vertebral (V) anorectal (A) cardiac (C) tracheoesophageal (TE) renal (L) and limb (L) anomalies, without a known common cause. We performed array comparative genomic hybridization (array CGH) and DNA sequencing of the candidate genes PCSK5, HOXD13 and CHD7 to investigate the role of copy number variants (CNV) and single gene defects in 39 patients and fetal cases with VACTERL association or a VACTERL-like phenotype. We identified pathogenic gene dose alterations in 2/39 patients (5%) and a pathogenic mutation in CHD7 in one patient, while single nucleotide variants of unclear significance were detected in PCSK5. We concluded that copy number variants are not common causes of VACTERL association and that CHARGE and VACTERL syndromes represent important differential diagnoses. Study IV In this study, we have investigated the hypothesis that genetic mosaicism in malformed organs could be an underlying cause of congenital malformations. Array CGH analyses using DNA derived from cardiac tissue in 23 patients with congenital heart malformations were performed, and findings of pathogenic or unclear variants were compared with presence in blood in the same individuals. We identified pathogenic gene dose alterations in 2/23 patients (9%) and did not find evidence for mosaicism. We concluded that identification of copy number variants are important in individual cases of congenital malformations and that genetic mosaicism warrants further study using other molecular genetic technologies. Study V We have studied the presence of copy number variants in 25 patients with congenital anorectal malformations, esophageal atresia and hydronephrosis using array CGH analysis and identified pathogenic variants in 2/25 cases (8%). We describe a mosaic structural variant of tetrasomy 15 identified in a patient with syndromic esophageal atresia, and report a novel putative susceptibility region for esophageal atresia. Mosaicism for pathogenic or unclear variants was investigated in both tissue and blood in eight cases and did not reveal discrepancies. The study shows importance of copy number analysis in individual patients with gastrointestinal malformations. General conclusions from our studies are that tissue-specific genetic mosaicism for copy number variants does not appear to be a common cause of congenital malformations and that CNV analysis is important in patients with congenital malformations as identification of high penetrance variants in some families markedly improves accuracy of recurrence risk estimations in these families.
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