| 1. |
- Adewumi, Oluseun, et al.
(författare)
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Characterization of human embryonic stem cell lines by the International Stem Cell Initiative
- 2007
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Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 25:7, s. 803-816
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Tidskriftsartikel (refereegranskat)abstract
- The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue- nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allele-specific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected.
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| 2. |
- Halvorsen, Matthew, et al.
(författare)
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Increased burden of ultra-rare structural variants localizing to boundaries of topologically associated domains in schizophrenia
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1, s. 1842-
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Tidskriftsartikel (refereegranskat)abstract
- Despite considerable progress in schizophrenia genetics, most findings have been for large rare structural variants and common variants in well-imputed regions with few genes implicated from exome sequencing. Whole genome sequencing (WGS) can potentially provide a more complete enumeration of etiological genetic variation apart from the exome and regions of high linkage disequilibrium. We analyze high-coverage WGS data from 1162 Swedish schizophrenia cases and 936 ancestry-matched population controls. Our main objective is to evaluate the contribution to schizophrenia etiology from a variety of genetic variants accessible to WGS but not by previous technologies. Our results suggest that ultra-rare structural variants that affect the boundaries of topologically associated domains (TADs) increase risk for schizophrenia. Alterations in TAD boundaries may lead to dysregulation of gene expression. Future mechanistic studies will be needed to determine the precise functional effects of these variants on biology.
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| 3. |
- Magnusson, Patrik K. E., et al.
(författare)
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One CNV Discordance in NRXN1 Observed Upon Genome-wide Screening in 38 Pairs of Adult Healthy Monozygotic Twins
- 2016
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Ingår i: Twin Research and Human Genetics. - : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 19:2, s. 97-103
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Tidskriftsartikel (refereegranskat)abstract
- Monozygotic (MZ) twins stem from the same single fertilized egg and therefore share all their inherited genetic variation. This is one of the unequivocal facts on which genetic epidemiology and twin studies are based. To what extent this also implies that MZ twins share genotypes in adult tissues is not precisely established, but a common pragmatic assumption is that MZ twins are 100% genetically identical also in adult tissues. During the past decade, this view has been challenged by several reports, with observations of differences in post-zygotic copy number variations (CNVs) between members of the same MZ pair. In this study, we performed a systematic search for differences of CNVs within 38 adult MZ pairs who had been misclassified as dizygotic (DZ) twins by questionnaire-based assessment. Initial scoring by PennCNV suggested a total of 967 CNV discor dances. The within-pair correlation in number of CNVs detected was strongly dependent on confidence score filtering and reached a plateau of r = 0.8 when restricting to CNVs detected with confidence score larger than 50. The top-ranked discordances were subsequently selected for validation by quantitative polymerase chain reaction (qPCR), from which one single similar to 120kb deletion in NRXN1 on chromosome 2 (bp 51017111-51136802) was validated. Despite involving an exon, no sign of cognitive/mental consequences was apparent in the affected twin pair, potentially reflecting limited or lack of expression of the transcripts containing this exon in nerve/brain.
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| 4. |
- Song, Jie, et al.
(författare)
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THE IMPACT OF EDUCATIONAL ATTAINMENT, INTELLIGENCE AND INTELLECTUAL DISABILITY ON SCHIZOPHRENIA : A SWEDISH POPULATION-BASED REGISTER AND GENETIC STUDY
- 2021
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Ingår i: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 51, s. e137-e138
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Schizophrenia (SCZ) is highly heterogenous and no subtypes have been established to have good clinical utility in characterizing treatment response or longitudinal course. Cognitive impairment is one of the core clinical features of SCZ and a determinant of poorer outcome. Genetic overlap between SCZ and cognitive ability is complex, with limited studies of comprehensive epidemiological and genomic evidence.Methods: To comprehensively examine the relation between SCZ and three cognitive traits, educational attainment (EDU), premorbid cognitive ability, and intellectual disability (ID), we used two samples from Sweden: a national cohort (13 738 SCZ cases and 3 677 172 controls) and a subsample with comprehensive genetic data (4 992 cases and 6 009 controls).Results: Population-based analyses showed worse cognition as risk factors for SCZ, and the pedigree genetic correlations between them were comparable with estimations from common genetic variants. In the genotyped subsample, premorbid cognitive ability and EDU were associated positively with their genetic risk score (GRS) and negatively with total number of rare exonic variants. The total size of copy number variants (CNV) deletions was associated with premorbid cognitive ability in controls. Finally, by applying an empirical clustering method, we dissect SCZ cases into four subgroups, defined by sex and ID. In particular, female cases with ID showed higher suicide-related events in the population cohort, and male-ID cases in genetic subsample had higher CNV and rare exonic burdens.Discussion: In conclusion, we found extensive evidence of a robust relation between cognitive ability and SCZ, underscoring the importance of cognition in dissecting the heterogeneity of SCZ.
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| 5. |
- Sullivan, Patrick F., et al.
(författare)
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Leveraging base-pair mammalian constraint to understand genetic variation and human disease
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6643, s. 367-
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Tidskriftsartikel (refereegranskat)abstract
- Thousands of genomic regions have been associated with heritable human diseases, but attempts to elucidate biological mechanisms are impeded by an inability to discern which genomic positions are functionally important. Evolutionary constraint is a powerful predictor of function, agnostic to cell type or disease mechanism. Single-base phyloP scores from 240 mammals identified 3.3% of the human genome as significantly constrained and likely functional. We compared phyloP scores to genome annotation, association studies, copy-number variation, clinical genetics findings, and cancer data. Constrained positions are enriched for variants that explain common disease heritability more than other functional annotations. Our results improve variant annotation but also highlight that the regulatory landscape of the human genome still needs to be further explored and linked to disease.
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| 6. |
- Szatkiewicz, Jin, et al.
(författare)
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The genomics of major psychiatric disorders in a large pedigree from Northern Sweden
- 2019
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Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- We searched for genetic causes of major psychiatric disorders (bipolar disorder, schizoaffective disorder, and schizophrenia) in a large, densely affected pedigree from Northern Sweden that originated with three pairs of founders born around 1650. We applied a systematic genomic approach to the pedigree via karyotyping (N = 9), genome-wide SNP arrays (N = 418), whole-exome sequencing (N = 26), and whole-genome sequencing (N = 10). Comprehensive analysis did not identify plausible variants of strong effect. Rather, pedigree cases had significantly higher genetic risk scores compared to pedigree and community controls.
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