| 1. |
- Georgsson, Susanne, et al.
(författare)
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Knowledge and attitudes regarding non-invasive prenatal testing (NIPT) and preferences for risk information among high school students in Sweden
- 2017
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Ingår i: Journal of Genetic Counseling. - New York : Human Sciences Press. - 1059-7700 .- 1573-3599. ; 26:3, s. 447-454
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Tidskriftsartikel (refereegranskat)abstract
- Non-invasive prenatal testing (NIPT) was recently introduced for prenatal testing of genetic disorders. Cell-free fetal DNA is present in maternal blood during pregnancy and enables detection of fetal chromosome aberrations in a maternal blood sample. The public perspective to this new, simple method has not been illuminated. The views of young people (i.e. future parents) are important to develop suitable counseling strategies regarding prenatal testing. The aim was to explore Swedish high school students' attitudes, knowledge and preferences regarding NIPT. A questionnaire was completed by 305 students recruited from one high school in Stockholm, November and December 2014. Most students (80 %) considered prenatal testing as good. The majority (65 %) was positive or very positive towards NIPT and 62 % stated that they potentially would like to undergo the test if they or their partner was pregnant. The vast majority (94 %) requested further information about NIPT. Most students (61 %) preferred verbal information, whereas 20 % preferred information via the Internet. The majority of the high school students was positive towards prenatal testing and most was positive towards NIPT. Further, information was requested by the vast majority before making a decision about NIPT. Most of the students preferred verbal information and to a lesser extent information via the Internet. The attitudes, knowledge and preferences for risk information concerning NIPT in young adults are important, in order to increase knowledge on how to educate and inform future parents.
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| 2. |
- A Hulten, Maj, et al.
(författare)
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On the origin of the maternal age effect in trisomy 21 Down syndrome: the Oocyte Mosaicism Selection model
- 2010
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Ingår i: Reproduction. - 1470-1626 .- 1476-3990. ; 139:1, s. 1-9
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Forskningsöversikt (refereegranskat)abstract
- We have recently documented that trisomy 21 mosaicism is common in human foetal ovaries. On the basis of this observation we propose that the maternal age effect in Down syndrome (DS) is caused by the differential behaviour of trisomy 21 in relation to disomy 21 oocytes during development from foetal life until ovulation in adulthood. in particular, we suggest that trisomy 21 oocytes, lagging behind those that are disomic, may escape the timed pruning of the seven million in foetal life to the 300-400 finally selected for ovulation. The net effect of this preferential elimination will be an accumulation of trisomy 21 oocytes in the ovarian reserve of older women. We here highlight the implications of this Oocyte Mosaicism Selection (OMS) model with respect to the prevalent view that the maternal age effect is complex, dependent on many different biological and environmental factors. We examine conclusions drawn from recent large-scale studies in families, tracing DNA markers along the length of chromosome 21q between parents and DS children, in comparison to the OMS model. We conclude that these family linkage data are equally compatible with the maternal age effect originating from the accumulation of trisomy 21 oocytes with advancing maternal age. One relatively straightforward way to get to grips with what is actually going on in this regard would be to compare incidence of trisomy 21 oocytes (and their pairing configurations) in foetal ovaries with that in oocytes at the meiosis I stage from adult women.
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| 3. |
- Eriksson, Erik, et al.
(författare)
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Perceived Housing in Relation to Retirement and Relocation : A Qualitative Interview Study among Older Adults
- 2022
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 19:20
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Tidskriftsartikel (refereegranskat)abstract
- As people age the home environment becomes increasingly important. Retirement commonly leads to spending more time in one’s home, and relocating from your own home in older age could be associated with reduced health or wellbeing. The relationship between home and person is complex and perceived aspects of one’s housing such as social, emotional and cognitive ties are considered important factors for health and wellbeing. However, little is known about how perceived aspects of the home change in relation to retirement and relocation. This paper used Situational Analysis to explore, via situational mapping, how community dwelling older adults (aged 60–75) perceived their housing situation in relation to retirement and relocation. The results suggest complex relations between relocation/retirement and perceived housing, and between different aspects of perceived housing. Furthermore, the results suggest that the relationship between life transitions and perceived housing can be seen as bi-directional, where different life transitions affect aspects of perceived housing, and that perceived housing affects (decisions for) relocation. The results suggest complex relations between retirement and relocation, as well as other life transitions, and perceived aspects of one’s housing. It is important to consider these interactions to understand factors that affect health and wellbeing in older adults.
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| 4. |
- Gunnarsson, Carina, et al.
(författare)
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Optimerad lagring av biomassa : en strategisk innovationsagenda
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I dag finns stor kunskap inom området lagring av biomassa, även om kunskapen i delar är fragmenterad. Inom energiområdet finns problem med både lagringsförluster och arbetsmiljö. Vid lagring av grödor till foder och livsmedel är bibehållen kvalitet hos biomassan under lagring en förutsättning, och mycket forskning och utveckling har bedrivits inom detta område. Genom samverkan mellan olika områden skapar vi förutsättningar att tänka i nya banor och öka möjligheterna för en optimerad lagring av biomassa. Arbetet med agendan har gett nya gränsöverskridande diskussioner och samarbeten. Med en förväntad kraftigt ökad efterfrågan och därmed konkurrens om biomassa blir effektivitet och hållbarhet nyckelfaktorer för fortsatt god tillgång. Kontinuerliga förbättringar i alla led av tillförselkedjan är nödvändiga för att hantera dessa i grunden positiva marknadsförändringar. Ett billigare och mer homogent bio-bränsle från jord- och skogsbruk leder till ökad konkurrenskraft gentemot andra idag billigare bränslen. Vid biobaserad värme- och kraftvärmeproduktion står bränslet för en av de största kostnadsposterna, vilket gör hantering och lagring med låga förluster högt prioriterat. Biobränslen från jord- och skogsbruk har en hög fukthalt vid skörd, vilket innebär att de har låg lagringsstabilitet. För att få ned kostnaderna för hantering och lagring, och kunna leverera efterfrågade kvaliteter och därmed öka bio-bränslenas konkurrenskraft, behövs mer kunskap om vad som händer med bränslet under olika lagringsförhållanden med olika lagrings- och hanteringsmetoder. Grundläggande och fördjupade kunskaper för att bedöma lagringsstabiliten för biomassa, framför allt livsmedelsbaserade såsom spannmål och rapsfrö, finns och är helt nödvändig för att garantera livsmedelssäkerhet. Dessa erfarenheter kan användas för att öka kunskapen om lagringsstabilitet och lagringsförluster hos biomassa som helhet. Denna agenda har tagits fram i samverkan mellan forskare från jord- och skogsbruk samt representanter från råvaruproducenter och energibolag som slutanvändare. Agendans syfte är att skapa ett bra utgångs-läge för en effektivare hantering av biomassa genom kunskapsöverföring mellan branscher. Agendans mål är ta fram forskningsbehov för utveckling och innovationer inom området som ska leda till effektiv och kvalitetssäkrad hantering av biomassa. Fokus är användning av biomassa inom energisektorn. Agendan avgränsas till att omfatta primära och sekundära oförädlade biobränslen från skogsbruk och jordbruk samt återvunna trädbränslen för värme- och kraftvärmeproduktion för anläggningar större än 1 MW. Vår vision är att använda biobränslets fulla potential genom kontrollerad lagring med låga förluster som ger effektiva och lönsamma leveranser med förutsägbar och homogen kvalitet utan hälsorisker. Vid två workshops på JTI i Uppsala träffades deltagarna för att identifiera kunskapsluckor, forskningsbehov och aktiviteter. För att inkludera synpunkter från fler aktörer genomfördes telefonintervjuer med ytterligare personer med koppling till biomassalagring.
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| 5. |
- Howard, Heidi Carmen, et al.
(författare)
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Mapping uncertainty in genomics
- 2018
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Ingår i: Journal of Risk Research. - : ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD. - 1366-9877 .- 1466-4461. ; 21:2, s. 117-128
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Tidskriftsartikel (refereegranskat)abstract
- The relatively novel and dynamic science of genomics holds many unknowns for stakeholders, and in particular for researchers and clinicians, as well as for participants and patients. At a time when many authors predict a future in which genomic medicine will be the norm, it is particularly relevant to discuss the unknowns surrounding genetics and genomics, including the notions of risk and uncertainty. This article will present a discussion regarding the uncertainty pertaining specifically to high throughput sequencing approaches, including the topic of incidental findings. This discussion will be guided by a taxonomy of uncertainty conceptualised around three areas of uncertainty: the source of uncertainty, the issues of uncertainty and the loci of uncertainty. This taxonomy can be used as a tool by all stakeholders involved in genomics to help further understand and anticipate uncertainties in genomics. Furthermore, to better contextualize this information, and also because this contribution is born out of an international project titled Mind the Risk', which addresses risk information in genetics and genomics from many different disciplinary perspectives, another aim of this article is to briefly present the basic issues pertaining to the unknowns, risks, and uncertainties of genetics as well as genomics for an audience of non-geneticists. Ultimately, the mapping out of uncertainty in genomics should allow for a better characterization of the uncertainty and consequently for a better management and communication of these uncertainties to end-users (research participants and patients).
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| 6. |
- Hultén, Maj A, et al.
(författare)
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Germinal and Somatic Trisomy 21 Mosaicism: How Common is it, What are the Implications for Individual Carriers and How Does it Come About?
- 2010
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Ingår i: CURRENT GENOMICS. - : Bentham Science Publishers Ltd. - 1389-2029 .- 1875-5488. ; 11:6, s. 409-419
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Tidskriftsartikel (refereegranskat)abstract
- It is well known that varying degrees of mosaicism for Trisomy 21, primarily a combination of normal and Trisomy 21 cells within individual tissues, may exist in the human population. This involves both Trisomy 21 mosaicism occurring in the germ line and Trisomy 21 mosaicism documented in different somatic tissues, or indeed a combination of both in the same subjects. Information on the incidence of Trisomy 21 mosaicism in different tissue samples from people with clinical features of Down syndrome as well as in the general population is, however, still limited. One of the main reasons for this lack of detailed knowledge is the technological problem of its identification, where in particular low grade/cryptic Trisomy 21 mosaicism, i.e. occurring in less than 3-5% of the respective tissues, can only be ascertained by fluorescence in situ hybridization (FISH) methods on large cell populations from the different tissue samples. In this review we summarize current knowledge in this field with special reference to the question on the likely incidence of germinal and somatic Trisomy 21 mosaicism in the general population and its mechanisms of origin. We also highlight the reproductive and clinical implications of this type of aneuploidy mosaicism for individual carriers. We conclude that the risk of begetting a child with Trisomy 21 Down syndrome most likely is related to the incidence of Trisomy 21 cells in the germ line of any carrier parent. The clinical implications for individual carriers may likewise be dependent on the incidence of Trisomy 21 in the relevant somatic tissues. Remarkably, for example, there are indications that Trisomy 21 mosaicism will predispose carriers to conditions such as childhood leukemia and Alzheimers Disease but there is on the other hand a possibility that the risk of solid cancers may be substantially reduced.
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| 7. |
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| 8. |
- Hulten, Maj A., et al.
(författare)
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On the paternal origin of trisomy 21 Down syndrome
- 2010
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Ingår i: Molecular Cytogenetics. - London, UK : BioMed Central (BMC). - 1755-8166. ; 3, s. 4-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Down syndrome (DS), characterized by an extra free chromosome 21 is the most common genetic cause for congenital malformations and learning disability. It is well known that the extra chromosome 21 originates from the mother in more than 90% of cases, the incidence increases with maternal age and there is a high recurrence in young women. In a previous report we have presented data to indicate that maternal trisomy 21 (T21) ovarian mosaicism might provide the major causative factor underlying these patterns of DS inheritance. One important outstanding question concerns the reason why the extra chromosome 21 in DS rarely originates from the father, i.e. in less than 10% of T21 DS cases. We here report data indicating that one reason for this parental sex difference is a very much lower degree of fetal testicular in comparison to ovarian T21 mosaicism. Results: We used fluorescence in situ hybridisation (FISH) with two chromosome 21-specific probes to determine the copy number of chromosome 21 in fetal testicular cell nuclei from four male fetuses, following termination of pregnancy for a non-medical/social reason at gestational age 14-19 weeks. The cells studied were selected on the basis of their morphology alone, pending immunological specification of the relevant cell types. We could not detect any indication of testicular T21 mosaicism in any of these four male fetuses, when analysing at least 2000 cells per case (range 2038-3971, total 11.842). This result is highly statistically significant (p < 0.001) in comparison to the average of 0.54% ovarian T21 mosaicism (range 0.20-0.88%) that we identified in eight female fetuses analysing a total of 12.634 cells, as documented in a previous report in this journal. Conclusion: Based on these observations we suggest that there is a significant sex difference in degrees of fetal germ line T21 mosaicism. Thus, it would appear that most female fetuses are T21 ovarian mosaics, while in sharp contrast most male fetuses may be either very low grade T21 testicular mosaics or they may be non-mosaics. We further propose that this sex difference in germ line T21 mosaicism may explain the much less frequent paternal origin of T21 DS than maternal. The mechanisms underlying the DS cases, where the extra chromosome 21 does originate from the father, remains unknown and further studies in this respect are required.
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| 9. |
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| 10. |
- Iwarsson, Erik, et al.
(författare)
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Analysis of cell-free fetal DNA in maternal blood for detection of trisomy 21, 18 and 13 in a general pregnant population and in a high risk population - a systematic review and meta-analysis
- 2017
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : WILEY-BLACKWELL. - 0001-6349 .- 1600-0412. ; 96:1
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Forskningsöversikt (refereegranskat)abstract
- IntroductionThe aim of this study was to review the performance of non-invasive prenatal testing (NIPT) for detection of trisomy 21, 18 and 13 (T21, T18 and T13) in a general pregnant population as well as to update the data on high-risk pregnancies. Material and methodsSystematic review and meta-analysis. PubMed, Embase and the Cochrane Library were searched. Methodological quality was rated using QUADAS and scientific evidence using GRADE. Summary measures of diagnostic accuracy were calculated using a bivariate random-effects model. ResultsIn a general pregnant population, there is moderate evidence that the pooled sensitivity is 0.993 (95% CI 0.955-0.999) and specificity was 0.999 (95% CI 0.998-0.999) for the analysis of T21. Pooled sensitivity and specificity for T13 and T18 was not calculated in this population due to the low number of studies. In a high-risk pregnant population, there is moderate evidence that the pooled sensitivities for T21 and T18 are 0.998 (95% CI 0.981-0.999) and 0.977 (95% CI 0.958-0.987) respectively, and low evidence that the pooled sensitivity for T13 is 0.975 (95% CI 0.819-0.997). The pooled specificity for all three trisomies is 0.999 (95% CI 0.998-0.999). ConclusionsThis is the first meta-analysis using GRADE that shows that NIPT performs well as a screen for trisomy 21 in a general pregnant population. Although the false positive rate is low compared with first trimester combined screening, women should still be advised to confirm a positive result by invasive testing if termination of pregnancy is under consideration.
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| 11. |
- Iwarsson, Erik
(författare)
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Genetic studies in early embryos with emphasis on preimplantation genetic diagnosis
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It has been estimated that as much as 70-80% of all human conceptions do not develop to term. A majority of clinically recognisable pregnancies, which are miscarried, contain chromosome abnormalities. However, data from very early embryo development are difficult to obtain. The recent development of single-cell fluorescent in situ hybridisation (FISH) analysis makes it possible to study chromosome abnormalities and segregation in early embryos. Using preimplantation genetic diagnosis (PGD) for carriers of structural chromosome abnormalities, we were able to perform chromosome studies in embryos as well as evaluate a new diagnostic tool. These experiences were also successfully implemented in a clinical service. A new single needle approach to obtain blastomere biopsies from human preimplantation embryos was tested and subsequently applied to PGD. The method was first evaluated in a mouse system and shown to be compatible with a high degree of in vitro and in vivo development of biopsied mouse embryos. Successful human PGD was performed when this method was applied in our human PGD programme. By using FISH, the presence of aneuploidy and mosaicism in normally fertilised freeze-thawed human embryos of good morphology were studied. The study shows a high degree of numerical chromosome abnormalities and 72% of the embryos displayed one or more abnormal blastomeres for the chromosomes studied. These data show a slightly higher incidence of abnormal embryos compared to those obtained with FISH in non-cryopreserved embryos and confirm that the majority of preimplantation embryos fertilised in vitro contain abnormal blastomeres. The investigation on mosaicism and aneuploidy in preimplantation embryos was continued with the detailed analysis of embryos from translocation carriers undergoing PGD. A high number of mosaic/chaotic embryos (73%) for the chromosomes involved in the translocation were found. A second hybridisation with two additional probes not involved in the translocation showed that the degree of mosaicism in each embryo differed between the two hybridisations. The difference in the average degree of mosaicism for all embryos was 65% regarding the chromosomes involved in the translocation as compared to 35% for two control chromosomes. The chromosome segregation pattern in embryos from carriers of structural chromosome abnormalities was investigated. The distribution of balanced and unbalanced gametes was for the first time studied in a female inversion carrier and the analysis showed that half of the analysed embryos were balanced. Alternate segregation mode was the most common mode of segregation in Robertsonian (85% of the embryos) and reciprocal (50% of the embryos) translocation carriers. Carriers of structural chromosome abnormalities are at high risk of having children with a severe handicap. Assays for the selection of balanced embryos was established using FISH. The first cases of PGD in order to avoid chromosomal imbalance in the progeny of two carriers of chromosome abnormalities, a deletion on chromosome 22q11.2 (DiGeorge syndrome) and an inversion of chromosome 5, respectively, were described. In addition, 11 PGD cycles for carriers of Robertsonian and reciprocal translocations were presented. As these patients are at high risk of having children with a severe handicap, PGD may be an attractive alternative as it allows only unaffected embryos to be selected for transfer to the uterus and the need to terminate the pregnancy is thereby avoided.
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| 12. |
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| 13. |
- Kylberg, Marianne, et al.
(författare)
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Environmental barriers and use of mobility devices.
- 2013
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Ingår i: Assistive Technology : From Research to Practice - From Research to Practice. - 1383-813X. - 9781614993032 ; 33, s. 190-194
-
Bokkapitel (refereegranskat)abstract
- To describe outdoor barriers in the nearby home environments of very old people, and to investigate whether the presence of these environmental barriers differed between users and non-users of mobility devices (MDs). Method: Baseline data on 397 Swedish people aged 80-89 years, collected with a study-specific question on MD use and a subset of the environmental component of the Housing Enabler instrument, assessing the outdoor environment nearby home, were used. Descriptive statistics were used for data analysis.
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| 14. |
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| 15. |
- Leal, Gabriela Ferraz, et al.
(författare)
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Expanding the Clinical Spectrum of Phenotypes Caused by Pathogenic Variants in PLOD2
- 2018
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431. ; 33:4, s. 753-760
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Tidskriftsartikel (refereegranskat)abstract
- Osteogenesis imperfecta (OI) is a strikingly heterogeneous group of disorders with a broad range of phenotypic variations. It is also one of the differential diagnoses in bent bone dysplasias along with campomelic dysplasia and thanatophoric dysplasia and can usually be distinguished by decreased bone mineralization and bone fractures. Bent bone dysplasias also include syndromes such as kyphomelic dysplasia (MIM:211350) and mesomelic dysplasia Kozlowski-Reardon (MIM249710), both of which have been under debate regarding whether or not they are a real entity or simply a phenotypic manifestation of another dysplasia including OI. Bruck syndrome type 2 (BRKS2; MIM:609220) is a rare form of autosomal recessive OI caused by biallelic PLOD2 variants and is associated with congenital joint contractures with pterygia. In this report, we present six patients from four families with novel PLOD2 variants. All cases had multiple fractures. Other features ranged from prenatal lethal severe angulation of the long bones as in kyphomelic dysplasia and mesomelic dysplasia Kozlowski-Reardon through classical Bruck syndrome to moderate OI with normal joints. Two siblings with a kyphomelic dysplasia-like phenotype who were stillborn had compound heterozygous variants in PLOD2 (p.Asp585Val and p.Ser166*). One infant who succumbed at age 4 months had a bent bone phenotype phenotypically like skeletal dysplasia Kozlowski-Reardon (with mesomelic shortening, camptodactyly, retrognathia, cleft palate, skin dimples, but also with fractures). He was homozygous for the nonsense variant (p.Trp561*). Two siblings had various degrees of Bruck syndrome caused by the homozygous missense variant, p.His687Arg. Furthermore a boy with a clinical presentation of moderate OI had a possibly pathogenic homozygous variant p.Trp588Cys. Our experience of six patients with biallelic pathogenic variants in PLOD2 expands the phenotypic spectrum in the PLOD2-related phenotypes.
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| 16. |
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| 17. |
- Lindstrand, Anna, et al.
(författare)
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From cytogenetics to cytogenomics : whole-genome sequencing as a first-line test comprehensively captures the diverse spectrum of disease-causing genetic variation underlying intellectual disability
- 2019
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Ingår i: Genome Medicine. - : BMC. - 1756-994X. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSince different types of genetic variants, from single nucleotide variants (SNVs) to large chromosomal rearrangements, underlie intellectual disability, we evaluated the use of whole-genome sequencing (WGS) rather than chromosomal microarray analysis (CMA) as a first-line genetic diagnostic test.MethodsWe analyzed three cohorts with short-read WGS: (i) a retrospective cohort with validated copy number variants (CNVs) (cohort 1, n=68), (ii) individuals referred for monogenic multi-gene panels (cohort 2, n=156), and (iii) 100 prospective, consecutive cases referred to our center for CMA (cohort 3). Bioinformatic tools developed include FindSV, SVDB, Rhocall, Rhoviz, and vcf2cytosure.ResultsFirst, we validated our structural variant (SV)-calling pipeline on cohort 1, consisting of three trisomies and 79 deletions and duplications with a median size of 850kb (min 500bp, max 155Mb). All variants were detected. Second, we utilized the same pipeline in cohort 2 and analyzed with monogenic WGS panels, increasing the diagnostic yield to 8%. Next, cohort 3 was analyzed by both CMA and WGS. The WGS data was processed for large (>10kb) SVs genome-wide and for exonic SVs and SNVs in a panel of 887 genes linked to intellectual disability as well as genes matched to patient-specific Human Phenotype Ontology (HPO) phenotypes. This yielded a total of 25 pathogenic variants (SNVs or SVs), of which 12 were detected by CMA as well. We also applied short tandem repeat (STR) expansion detection and discovered one pathologic expansion in ATXN7. Finally, a case of Prader-Willi syndrome with uniparental disomy (UPD) was validated in the WGS data.Important positional information was obtained in all cohorts. Remarkably, 7% of the analyzed cases harbored complex structural variants, as exemplified by a ring chromosome and two duplications found to be an insertional translocation and part of a cryptic unbalanced translocation, respectively.ConclusionThe overall diagnostic rate of 27% was more than doubled compared to clinical microarray (12%). Using WGS, we detected a wide range of SVs with high accuracy. Since the WGS data also allowed for analysis of SNVs, UPD, and STRs, it represents a powerful comprehensive genetic test in a clinical diagnostic laboratory setting.
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| 18. |
- Norling, Ameli, et al.
(författare)
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Novel candidate genes for 46,XY gonadal dysgenesis identified by a customized 1 M array-CGH platform
- 2013
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Ingår i: European Journal of Medical Genetics. - : Elsevier BV. - 1769-7212 .- 1878-0849. ; 56:12, s. 661-668
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Tidskriftsartikel (refereegranskat)abstract
- Half of all patients with a disorder of sex development (DSD) do not receive a specific molecular diagnosis. Comparative genomic hybridization (CGH) can detect copy number changes causing gene haploinsufficiency or over-expression that can lead to impaired gonadal development and gonadal DSD. The purpose of this study was to identify novel candidate genes for 46,XY gonadal dysgenesis (GD) using a customized 1 M array-CGH platform with whole-genome coverage and probe enrichment targeting 78 genes involved in sex development. Fourteen patients with 46,XY gonadal DSD were enrolled in the study. Nine individuals were analyzed by array CGH. All patients were included in a follow up sequencing study of candidate genes. Three novel candidate regions for 46,XY GD were identified in two patients. An interstitial duplication of the SUPT3H gene and a deletion of C2ORF80 were detected in a pair of affected siblings. Sequence analysis of these genes in all patients revealed no additional mutations. A large duplication highlighting PIP5K1B, PRKACG and FAM189A2 as candidates for 46, XY GD, were also detected. All five genes are expressed in testicular tissues, and one is shown to cause gonadal DSD in mice. However detailed functional information is lacking for these genes.
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| 19. |
- Paulrud, Susanne, et al.
(författare)
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Innovationskluster för internationalisering inom bioenergiområdet - förstudie
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Bioenergy contributes to a sustainable energy mix in most countries worldwide, is the largest renewable energy generation and has a global development potential. Bioenergy today accounts for 60 percent of all renewable energy in the EU: 11 percent of all used energy, compared with 7 percent for all other renewable energy sources. However, the market for Swedish bioenergy and bioenergy technology in Sweden has decreased. Partly because our domestic market for new district heating installations has already been expanded and partly because the competition from electricity heating through energy efficient heat pumps in the residential segment takes over the exchange market. In order for Swedish know-how and products to grow, increased exports and visibility are important. An innovation cluster for internationalization in the bioenergy field cre-ates a meeting place that facilitates involved bioenergy companies and organizations to create sustainable growth inside and outside their own industry.
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| 20. |
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| 21. |
- Sahlin, Ellika, et al.
(författare)
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Identification of putative pathogenic single nucleotide variants (SNVs) in genes associated with heart disease in 290 cases of stillbirth
- 2019
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of stillbirth in Sweden has essentially remained constant since the 1980s, and despite thorough investigation, many cases remain unexplained. It has been suggested that a proportion of stillbirth cases is caused by heart disease, mainly channelopathies. The aim of this study was to analyze DNA from 290 stillbirth cases without chromosomal abnormalities for pathogenic single nucleotide variants (SNVs) in 70 genes associated with cardiac channelopathies and cardiomyopathies. The HaloPlex Target Enrichment System (Agilent Technologies) was utilized to prepare sequencing libraries which were sequenced on the Illumina NextSeq platform. We found that 12.1% of the 290 investigated stillbirth cases had one (n = 31) or two (n = 4) variants with evidence supporting pathogenicity, i.e. loss-of-function variants (nonsense, frameshift, splice site substitutions), evidence from functional studies, or previous identification of the variants in affected individuals. Regarding identified putative pathogenic variants in genes associated with channelopathies, the prevalence was significantly higher in the stillbirth cohort (n = 23, 7.93%) than the corresponding prevalence of the same variants in the non-Finnish European population of the Exome Aggregation Consortium (2.70%, pamp;lt;0.001) and SweGen, (2.30%, pamp;lt;0.001). Our results give further support to the hypothesis that cardiac channelopathies might contribute to stillbirth. Screening for pathogenic SNVs in genes associated with heart disease might be a valuable complement for stillbirth cases where todays conventional investigation does not reveal the underlying cause of fetal demise.
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| 22. |
- Sahlin, Ellika, et al.
(författare)
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Positive Attitudes towards Non-Invasive Prenatal Testing (NIPT) in a Swedish Cohort of 1,003 Pregnant Women
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The clinical utilization of non-invasive prenatal testing (NIPT) for identification of fetal aneuploidies is expanding worldwide. The aim of this study was to gain an increased understanding of pregnant women's awareness, attitudes, preferences for risk information and decision-making concerning prenatal examinations with emphasis on NIPT, before its introduction into Swedish healthcare.METHOD: Pregnant women were recruited to fill in a questionnaire, including multiple-choice questions and Likert scales, at nine maternity clinics located in different areas of Stockholm, Sweden.RESULTS: In total, 1,003 women participated in the study (86% consent rate). The vast majority (90.7%) considered examinations aiming to detect fetal abnormalities to be good. Regarding NIPT, 59.8% stated that they had heard about the method previously, yet 74.0% would like to use the test if available. The main factor affecting the women's decision to undergo prenatal chromosomal screening was worry about the baby's health (82.5%), followed by the urge to have as much information as possible about the fetus (54.5%). Most women (79.9%) preferred to receive NIPT information orally.CONCLUSION: The overwhelming majority of a cohort of 1,003 pregnant women considered prenatal examinations good. Moreover, the majority had a positive attitude towards NIPT and would like to use the test if available.
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| 23. |
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| 24. |
- Wedenoja, Satu, et al.
(författare)
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Fetal HLA-G mediated immune tolerance and interferon response in preeclampsia
- 2020
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 59
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fetal immune tolerance is crucial for pregnancy success. We studied the link between preeclampsia, a severe pregnancy disorder with uncertain pathogenesis, and fetal human leukocyte antigen G (HLA-G) and other genes regulating maternal immune responses.Methods: We assessed sex ratios and regulatory HLA-G haplotypes in population cohorts and series of preeclampsia and stillbirth. We studied placental mRNA expression of 136 genes by sequencing and HLA-G and interferon alpha (IFNα) protein expression by immunohistochemistry.Findings: We found underrepresentation of males in preeclamptic births, especially those delivered preterm or small for gestational age. Balancing selection at HLA-G associated with the sex ratio, stillbirth, and preeclampsia. We observed downregulation of HLA-G, its receptors, and many other tolerogenic genes, and marked upregulation of IFNA1 in preeclamptic placentas.Interpretation: These findings indicate that an evolutionary trade-off between immune tolerance and protection against infections at the maternal-fetal interface promotes genetic diversity in fetal HLA-G, thereby affecting survival, preeclampsia, and sex ratio. We highlight IFNA1 as a potential mediator of preeclampsia and a target for therapeutic trials.
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| 25. |
- 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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| 26. |
- Winberg, Johanna, et al.
(författare)
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Mutation Screening and Array Comparative Genomic Hybridization Using a 180K Oligonucleotide Array in VACTERL Association
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:1, s. e85313-
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Tidskriftsartikel (refereegranskat)abstract
- In order to identify genetic causes of VACTERL association (V vertebral defects, A anorectal malformations, C cardiac defects, T tracheoesofageal fistula, E esophageal atresia, R renal anomalies, L limb deformities), we have collected DNA samples from 20 patients diagnosed with VACTERL or with a VACTERL-like phenotype as well as samples from 19 aborted fetal cases with VACTERL. To investigate the importance of gene dose alterations in the genetic etiology of VACTERL association we have performed a systematic analysis of this cohort using a 180K array comparative genomic hybridization (array-CGH) platform. In addition, to further clarify the significance of PCSK5, HOXD13 and CHD7 genes in the VACTERL phenotype, mutation screening has been performed. We identified pathogenic gene dose imbalances in two fetal cases; a hemizygous deletion of the FANCB gene and a (9;18)(p24;q12) unbalanced translocation. In addition, one pathogenic mutation in CHD7 was detected, while no apparent disease-causing mutations were found in HOXD13 or PCSK5. Our study shows that although large gene dose alterations do not seem to be a common cause in VACTERL association, array-CGH is still important in clinical diagnostics to identify disease cause in individual cases.
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