| 1. |
- Acevedo, Nathalie, et al.
(författare)
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Genetic Variants in CHIA and CHI3L1 Are Associated with the IgE Response to the Ascaris Resistance Marker ABA-1 and the Birch Pollen Allergen Bet v 1
- 2016
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Ingår i: plos one. - : Public Library of Science (PLoS). - 1932-6203. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Helminth infections and allergic diseases are associated with IgE hyperresponsiveness but the genetics of this phenotype remain to be defined. Susceptibility to Ascaris lumbricoides infection and antibody levels to this helminth are associated with polymorphisms in locus 13q33-34. We aimed to explore this and other genomic regions to identify genetic variants associated with the IgE responsiveness in humans. Forty-eight subjects from Cartagena, Colombia, with extreme values of specific IgE to Ascaris and ABA-1, a resistance marker of this nematode, were selected for targeted resequencing. Burden analyses were done comparing extreme groups for IgE values. One-hundred one SNPs were genotyped in 1258 individuals of two well-characterized populations from Colombia and Sweden. Two low-frequency coding variants in the gene encoding the Acidic Mammalian Chitinase (CHIA rs79500525, rs139812869, tagged by rs10494133) were found enriched in high IgE responders to ABA-1 and confirmed by genetic association analyses. The SNP rs4950928 in the Chitinase 3 Like 1 gene (CHI3L1) was associated with high IgE to ABA-1 in Colombians and with high IgE to Bet v 1 in the Swedish population. CHIA rs10494133 and ABDH13 rs3783118 were associated with IgE responses to Ascaris. SNPs in the Tumor Necrosis Factor Superfamily Member 13b gene (TNFSF13B) encoding the cytokine B cell activating Factor were associated with high levels of total IgE in both populations. This is the first report on the association between low-frequency and common variants in the chitinases- related genes CHIA and CHI3L1 with the intensity of specific IgE to ABA-1 in a population naturally exposed to Ascaris and with Bet v 1 in a Swedish population. Our results add new information about the genetic influences of human IgE responsiveness; since the genes encode for enzymes involved in the immune response to parasitic infections, they could be helpful for understanding helminth immunity and allergic responses. We also confirmed that TNFSF13B has an important and conserved role in the regulation of total IgE levels, which supports potential evolutionary links between helminth immunity and allergic response.
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| 2. |
- Agaton, Charlotta, et al.
(författare)
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Gene expression analysis by signature pyrosequencing
- 2002
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Ingår i: Gene. - 0378-1119 .- 1879-0038. ; 289:1-2, s. 31-39
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Tidskriftsartikel (refereegranskat)abstract
- We describe a novel method for transcript profiling based on high-throughput parallel sequencing of signature tags using a non-gel-based microtiter plate format. The method relies on the identification of cDNA clones by pyrosequencing of the region corresponding to the 3'-end of the mRNA preceding the poly(A) tail. Simultaneously, the method can be used for gene discovery, since tags corresponding to unknown genes can be further characterized by extended sequencing. The protocol was validated using a model system for human atherosclerosis. Two 3'-tagged cDNA libraries, representing macrophages and foam cells, which are key components in the development of atherosclerotic plaques, were constructed using a solid phase approach. The libraries were analyzed by pyrosequencing, giving on average 25 bases. As a control, conventional expressed sequence tag (EST) sequencing using slab gel electrophoresis was performed. Homology searches were used to identify the genes corresponding to each tag. Comparisons with EST sequencing showed identical, unique matches in the majority of cases when the pyrosignature was at least 18 bases. A visualization tool was developed to facilitate differential analysis using a virtual chip format. The analysis resulted in identification of genes with possible relevance for development of atherosclerosis. The use of the method for automated massive parallel signature sequencing is discussed.
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| 3. |
- Ahmed, Engy, et al.
(författare)
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Archaeal community changes in Lateglacial lake sediments: Evidence from ancient DNA
- 2018
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 181, s. 19-29
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Tidskriftsartikel (refereegranskat)abstract
- The Lateglacial/early Holocene sediments from the ancient lake at Hässeldala Port, southern Sweden provide an important archive for the environmental and climatic shifts at the end of the last ice age and the transition into the present Interglacial. The existing multi-proxy data set highlights the complex interplay of physical and ecological changes in response to climatic shifts and lake status changes. Yet, it remains unclear how microorganisms, such as Archaea, which do not leave microscopic features in the sedimentary record, were affected by these climatic shifts. Here we present the metagenomic data set of Hässeldala Port with a special focus on the abundance and biodiversity of Archaea. This allows reconstructing for the first time the temporal succession of major Archaea groups between 13.9 and 10.8 ka BP by using ancient environmental DNA metagenomics and fossil archaeal cell membrane lipids. We then evaluate to which extent these findings reflect physical changes of the lake system, due to changes in lake-water summer temperature and seasonal lake-ice cover. We show that variations in archaeal composition and diversity were related to a variety of factors (e.g., changes in lake water temperature, duration of lake ice cover, rapid sediment infilling), which influenced bottom water conditions and the sediment-water interface. Methanogenic Archaea dominated during the Allerød and Younger Dryas pollen zones, when the ancient lake was likely stratified and anoxic for large parts of the year. The increase in archaeal diversity at the Younger Dryas/Holocene transition is explained by sediment infilling and formation of a mire/peatbog.
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| 4. |
- Bergfeldt, Nora, et al.
(författare)
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Identification of microbial pathogens in Neolithic Scandinavian humans
- 2024
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Ingår i: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 14
-
Tidskriftsartikel (refereegranskat)abstract
- With the Neolithic transition, human lifestyle shifted from hunting and gathering to farming. This change altered subsistence patterns, cultural expression, and population structures as shown by the archaeological/zooarchaeological record, as well as by stable isotope and ancient DNA data. Here, we used metagenomic data to analyse if the transitions also impacted the microbiome composition in 25 Mesolithic and Neolithic hunter-gatherers and 13 Neolithic farmers from several Scandinavian Stone Age cultural contexts. Salmonella enterica, a bacterium that may have been the cause of death for the infected individuals, was found in two Neolithic samples from Battle Axe culture contexts. Several species of the bacterial genus Yersinia were found in Neolithic individuals from Funnel Beaker culture contexts as well as from later Neolithic context. Transmission of e.g. Y. enterocolitica may have been facilitated by the denser populations in agricultural contexts.
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| 5. |
- Bergfeldt, Nora, et al.
(författare)
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Identification of microbial pathogens in Neolithic Scandinavian humans
- 2024
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Ingår i: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- With the Neolithic transition, human lifestyle shifted from hunting and gathering to farming. This change altered subsistence patterns, cultural expression, and population structures as shown by the archaeological/zooarchaeological record, as well as by stable isotope and ancient DNA data. Here, we used metagenomic data to analyse if the transitions also impacted the microbiome composition in 25 Mesolithic and Neolithic hunter-gatherers and 13 Neolithic farmers from several Scandinavian Stone Age cultural contexts. Salmonella enterica, a bacterium that may have been the cause of death for the infected individuals, was found in two Neolithic samples from Battle Axe culture contexts. Several species of the bacterial genus Yersinia were found in Neolithic individuals from Funnel Beaker culture contexts as well as from later Neolithic context. Transmission of e.g. Y. enterocolitica may have been facilitated by the denser populations in agricultural contexts.
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| 6. |
- Bysani, Madhusudhan, et al.
(författare)
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ATAC-seq reveals alterations in open chromatin in pancreatic islets from subjects with type 2 diabetes
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Impaired insulin secretion from pancreatic islets is a hallmark of type 2 diabetes (T2D). Altered chromatin structure may contribute to the disease. We therefore studied the impact of T2D on open chromatin in human pancreatic islets. We used assay for transposase-accessible chromatin using sequencing (ATAC-seq) to profile open chromatin in islets from T2D and non-diabetic donors. We identified 57,105 and 53,284 ATAC-seq peaks representing open chromatin regions in islets of nondiabetic and diabetic donors, respectively. The majority of ATAC-seq peaks mapped near transcription start sites. Additionally, peaks were enriched in enhancer regions and in regions where islet-specific transcription factors (TFs), e.g. FOXA2, MAFB, NKX2.2, NKX6.1 and PDX1, bind. Islet ATAC-seq peaks overlap with 13 SNPs associated with T2D (e.g. rs7903146, rs2237897, rs757209, rs11708067 and rs878521 near TCF7L2, KCNQ1, HNF1B, ADCY5 and GCK, respectively) and with additional 67 SNPs in LD with known T2D SNPs (e.g. SNPs annotated to GIPR, KCNJ11, GLIS3, IGF2BP2, FTO and PPARG). There was enrichment of open chromatin regions near highly expressed genes in human islets. Moreover, 1,078 open chromatin peaks, annotated to 898 genes, differed in prevalence between diabetic and non-diabetic islet donors. Some of these peaks are annotated to candidate genes for T2D and islet dysfunction (e.g. HHEX, HMGA2, GLIS3, MTNR1B and PARK2) and some overlap with SNPs associated with T2D (e.g. rs3821943 near WFS1 and rs508419 near ANK1). Enhancer regions and motifs specific to key TFs including BACH2, FOXO1, FOXA2, NEUROD1, MAFA and PDX1 were enriched in differential islet ATAC-seq peaks of T2D versus non-diabetic donors. Our study provides new understanding into how T2D alters the chromatin landscape, and thereby accessibility for TFs and gene expression, in human pancreatic islets.
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| 7. |
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| 8. |
- Dalin, Martin, 1982, et al.
(författare)
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Massive parallel sequencing questions the pathogenic role of missense variants in dilated cardiomyopathy
- 2017
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 228, s. 742-748
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Tidskriftsartikel (refereegranskat)abstract
- Background: Germline genetic variants are an important cause of dilated cardiomyopathy (DCM). However, recent sequencing studies have revealed rare variants in DCM-associated genes also in individuals without known heart disease. In this study, we investigate variant prevalence and genotype-phenotype correlations in Swedish DCM patients, and compare their genetic variants to those detected in reference cohorts. Methods and results: We sequenced the coding regions of 41 DCM-associated genes in 176 unrelated patients with idiopathic DCM and found 102 protein-altering variants with an allele frequency of <0.04% in reference cohorts; the majority were missense variants not previously described in DCM. Fifty-five (31%) patients had one variant, and 24 (14%) patients had two or more variants in the analysed genes. Detection of genetic variants in any gene, and in LMNA, MYII7 or TTN alone, was associated with early onset disease and reduced transplant-free survival. As expected, nonsense and frameshift variants were more common in DCM patients than in healthy individuals of the reference cohort 1000 Genomes Europeans. Surprisingly however, the prevalence, conservation and pathogenicity scores, and localization of missense variants were similar in DCM patients and healthy reference individuals. Conclusion: To our knowledge, this is the first study to identify correlations between genotype and prognosis when sequencing a large number of genes in unselected DCM patients. The similar distribution of missense variants in DCM patients and healthy reference individuals questions the pathogenic role of many variants, and suggests that results from genetic testing of DCM patients should be interpreted with caution.
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| 9. |
- Grüning, Björn, et al.
(författare)
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Bioconda: A sustainable and comprehensive software distribution for the life sciences
- 2017
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We present Bioconda (https://bioconda.github.io), a distribution of bioinformatics software for the lightweight, multi-platform and language-agnostic package manager Conda. Currently, Bioconda offers a collection of over 3000 software packages, which is continuously maintained, updated, and extended by a growing global community of more than 200 contributors. Bioconda improves analysis reproducibility by allowing users to define isolated environments with defined software versions, all of which are easily installed and managed without administrative privileges.
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| 10. |
- Imanishi, T., et al.
(författare)
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Integrative annotation of 21,037 human genes validated by full-length cDNA clones
- 2004
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 2:6, s. 856-875
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Tidskriftsartikel (refereegranskat)abstract
- The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.
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| 11. |
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| 12. |
- Lauterbur, M. Elise, et al.
(författare)
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Expanding the stdpopsim species catalog, and lessons learned for realistic genome simulations
- 2023
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Simulation is a key tool in population genetics for both methods development and empirical research, but producing simulations that recapitulate the main features of genomic datasets remains a major obstacle. Today, more realistic simulations are possible thanks to large increases in the quantity and quality of available genetic data, and the sophistication of inference and simulation software. However, implementing these simulations still requires substantial time and specialized knowledge. These challenges are especially pronounced for simulating genomes for species that are not well-studied, since it is not always clear what information is required to produce simulations with a level of realism sufficient to confidently answer a given question. The community-developed framework stdpopsim seeks to lower this barrier by facilitating the simulation of complex population genetic models using up-to-date information. The initial version of stdpopsim focused on establishing this framework using six well-characterized model species (Adrion et al., 2020). Here, we report on major improvements made in the new release of stdpopsim (version 0.2), which includes a significant expansion of the species catalog and substantial additions to simulation capabilities. Features added to improve the realism of the simulated genomes include non-crossover recombination and provision of species-specific genomic annotations. Through community-driven efforts, we expanded the number of species in the catalog more than threefold and broadened coverage across the tree of life. During the process of expanding the catalog, we have identified common sticking points and developed the best practices for setting up genome-scale simulations. We describe the input data required for generating a realistic simulation, suggest good practices for obtaining the relevant information from the literature, and discuss common pitfalls and major considerations. These improvements to stdpopsim aim to further promote the use of realistic whole-genome population genetic simulations, especially in non-model organisms, making them available, transparent, and accessible to everyone.
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| 13. |
- Nguyen, Diem, PhD, et al.
(författare)
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Transposon- and Genome Dynamics in the Fungal Genus Neurospora: Insights from Nearly Gapless Genome Assemblies
- 2022
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Ingår i: Fungal Genetics Reports. - : New Prairie Press. - 1941-4765. ; 66:1
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Tidskriftsartikel (refereegranskat)abstract
- A large portion of nuclear DNA is composed of transposable element (TE) sequences, whose transposition is controlled by diverse host defense strategies in order to maintain genomic integrity. One such strategy is the fungal-specific Repeat-Induced Point mutation (RIP) that hyper-mutates repetitive DNA sequences. While RIP is found across Fungi, it has been shown to vary in efficiency. The filamentous ascomycete Neurospora crassa has been a pioneer in the study of RIP, but data on TEs and RIP from other species in the genus is limited. In this study, we investigated 18 nearly gapless genome assemblies of ten Neurospora species, which diverged from a common ancestor about 7 MYA, to determine and compare genome-wide TE distribution and their associated RIP patterns. Four of these assemblies, generated by PacBio technology, represent new genomic datasets. We showed that the TE contents (8.7-18.9%) covary with genome sizes that range between 37.8-43.9 Mb. Degraded copies of Long Terminal Repeat (LTR) retrotransposons were abundant among the identified TEs, and these are distributed across the genome at varying frequencies. In all investigated Neurospora genomes, TE sequences had signs of numerous C-to-T substitutions, suggesting that RIP occurred in all species, and accordingly, RIP signatures correlated with TE-dense regions in all genomes. In conclusion, essentially gapless genome assemblies allowed us to identify TEs in Neurospora genomes, and reveal that TEs contribute to genome size variation in this group. Our study suggests that TEs and RIP are highly correlated in each examined Neurospora species, and hence, the pattern of interaction is conserved over the investigated evolutionary timescale. Finally, with our results, we verify that RIP signatures can be used to facilitate the identification of TE-rich regions in the genome. The comprehensive genomic dataset of Neurospora is a rich resource for further in- depth analyses of fungal genomes by the community.
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| 14. |
- Parducci, Laura, 1965-, et al.
(författare)
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Shotgun Environmental DNA, Pollen, and Macrofossil Analysis of Lateglacial Lake Sediments From Southern Sweden
- 2019
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Ingår i: Frontiers in Ecology and Evolution. - : Frontiers Media SA. - 2296-701X. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- The lake sediments of Hasseldala Port in south-east Sweden provide an archive of local and regional environmental conditions similar to 14.5-9.5 ka BP (thousand years before present) and allow testing DNA sequencing techniques to reconstruct past vegetation changes. We combined shotgun sequencing with plant micro- and macrofossil analyses to investigate sediments dating to the Allerod (14.1-12.7 ka BP), Younger Dryas (12.7-11.7 ka BP), and Preboreal (<11.7 ka BP). Number of reads and taxa were not associated with sample age or organic content. This suggests that, beyond the initial rapid degradation, DNA is still present. The proportion of recovered plant DNA was low, but allowed identifying an important number of plant taxa, thus adding valid information on the composition of the local vegetation. Importantly, DNA provides a stronger signal of plant community changes than plant micro- and plant macrofossil analyses alone, since a larger number of new taxa were recorded in Younger Dryas samples. A comparison between the three proxies highlights differences and similarities and supports earlier findings that plants growing close to or within a lake are recorded by DNA. Plant macrofossil remains moreover show that tree birch was present close to the ancient lake since the Allerod; together with the DNA results, this indicates that boreal to subarctic climatic conditions also prevailed during the cold Younger Dryas interval. Increasing DNA reference libraries and enrichment strategies prior to sequencing are necessary to improve the potential and accuracy of plant identification using the shotgun metagenomic approach.
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| 15. |
- Peyrard-Janvid, Myriam, et al.
(författare)
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Dominant Mutations in GRHL3 Cause Van der Woude Syndrome and Disrupt Oral Periderm Development
- 2014
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 94:1, s. 23-32
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in interferon regulatory factor 6 (IRF6) account for similar to 70% of cases of Van der Woude syndrome (VWS), the most common syndromic form of cleft lip and palate. In 8 of 45 VWS-affected families lacking a mutation in IRF6, we found coding mutations in grainyhead-like 3 (GRHL3). According to a zebrafish-based assay, the disease-associated GRHL3 mutations abrogated periderm development and were consistent with a dominant-negative effect, in contrast to haploinsufficiency seen in most VWS cases caused by IRF6 mutations. In mouse, all embryos lacking Grhl3 exhibited abnormal oral periderm and 17% developed a cleft palate. Analysis of the oral phenotype of double heterozygote (Irf6(+/-);Grhl3(+/-)) murine embryos failed to detect epistasis between the two genes, suggesting that they function in separate but convergent pathways during palatogenesis. Taken together, our data demonstrated that mutations in two genes, IRF6 and GRHL3, can lead to nearly identical phenotypes of orofacial cleft. They supported the hypotheses that both genes are essential for the presence of a functional oral periderm and that failure of this process contributes to VWS.
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| 16. |
- Pochon, Zoé, et al.
(författare)
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aMeta : an accurate and memory-efficient ancient metagenomic profiling workflow
- 2023
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Ingår i: Genome Biology. - : BioMed Central (BMC). - 1465-6906 .- 1474-760X. ; 24
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of microbial data from archaeological samples is a growing field with great potential for understanding ancient environments, lifestyles, and diseases. However, high error rates have been a challenge in ancient metagenomics, and the availability of computational frameworks that meet the demands of the field is limited. Here, we propose aMeta, an accurate metagenomic profiling workflow for ancient DNA designed to minimize the amount of false discoveries and computer memory requirements. Using simulated data, we benchmark aMeta against a current state-of-the-art workflow and demonstrate its superiority in microbial detection and authentication, as well as substantially lower usage of computer memory.
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| 17. |
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| 18. |
- Poelstra, Jelmer W., et al.
(författare)
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The genomic landscape underlying phenotypic integrity in the face of gene flow in crows
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 344:6190, s. 1410-1414
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Tidskriftsartikel (refereegranskat)abstract
- The importance, extent, and mode of interspecific gene flow for the evolution of species has long been debated. Characterization of genomic differentiation in a classic example of hybridization between all-black carrion crows and gray-coated hooded crows identified genome-wide introgression extending far beyond the morphological hybrid zone. Gene expression divergence was concentrated in pigmentation genes expressed in gray versus black feather follicles. Only a small number of narrow genomic islands exhibited resistance to gene flow. One prominent genomic region (<2 megabases) harbored 81 of all 82 fixed differences (of 8.4 million single-nucleotide polymorphisms in total) linking genes involved in pigmentation and in visual perception-a genomic signal reflecting color-mediated prezygotic isolation. Thus, localized genomic selection can cause marked heterogeneity in introgression landscapes while maintaining phenotypic divergence.
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| 19. |
- Sterky, Fredrik, et al.
(författare)
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A Populus EST resource for plant functional genomics
- 2004
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 101:38, s. 13951-13956
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Tidskriftsartikel (refereegranskat)abstract
- Trees present a life form of paramount importance for terrestrial ecosystems and human societies because of their ecological structure and physiological function and provision of energy and industrial materials. The genus Populus is the internationally accepted model for molecular tree biology. We have analyzed 102,019 Populus ESTs that clustered into 11,885 clusters and 12,759 singletons. We also provide >4,000 assembled full clone sequences to serve as a basis for the upcoming annotation of the Populus genome sequence. A public web-based EST database (POPULUSDB) provides digital expression profiles for 18 tissues that comprise the majority of differentiated organs. The coding content of Populus and Arabidopsis genomes shows very high similarity, indicating that differences between these annual and perennial angiosperm life forms result primarily from differences in gene regulation. The high similarity between Populus and Arabidopsis will allow studies of Populus to directly benefit from the detailed functional genomic information generated for Arabidopsis, enabling detailed insights into tree development and adaptation. These data will also valuable for functional genomic efforts in Arabidopsis.
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| 20. |
- Tuominen, Rainer, et al.
(författare)
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The Role of Germline Alterations in the DNA Damage Response Genes BRIP1 and BRCA2 in Melanoma Susceptibility
- 2016
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley-Blackwell. - 1045-2257 .- 1098-2264. ; 55:7, s. 601-611
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Tidskriftsartikel (refereegranskat)abstract
- We applied a targeted sequencing approach to identify germline mutations conferring a moderately to highly increased risk of cutaneous and uveal melanoma. Ninety-two high-risk melanoma patients were screened for inherited variation in 120 melanoma candidate genes. Observed gene variants were filtered based on frequency in reference populations, cosegregation with melanoma in families and predicted functional effect. Several novel or rare genetic variants in genes involved in DNA damage response, cell-cycle regulation and transcriptional control were identified in melanoma patients. Among identified genetic alterations was an extremely rare variant (minor allele frequency of 0.00008) in the BRIP1 gene that was found to cosegregate with the melanoma phenotype. We also found a rare nonsense variant in the BRCA2 gene (rs11571833), previously associated with cancer susceptibility but not with melanoma, which showed weak association with melanoma susceptibility in the Swedish population. Our results add to the growing knowledge about genetic factors associated with melanoma susceptibility and also emphasize the role of DNA damage response as an important factor in melanoma etiology.
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| 21. |
- Unneberg, Per, et al.
(författare)
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Analysis of 70,000 EST sequences to study divergence between two closely related Populus species
- 2005
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Ingår i: Tree Genetics & Genomes. - : Springer Science and Business Media LLC. - 1614-2942 .- 1614-2950. ; 1:3, s. 109-115
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Tidskriftsartikel (refereegranskat)abstract
- The Populus genus has evolved as the model organism for forest tree genomics, which has been further emphasised with the sequencing of the Populus trichocarpa genome. Populus species are widely spread over the Northern Hemisphere and provide a great source of genetic diversity, which can be used for mapping of quantitative trait loci, positional cloning, association mapping and studies in environmental adaptation. Collections of expressed sequence tags (ESTs) are rich sources in studies of genetic diversity. Here, we report on an in-depth analysis of 70,000 ESTs from two Populus species, Populus tremula and Populus trichocarpa. We present data on the level of conservation in transcript sequences and supply a collection of potential single nucleotide polymorphisms.
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| 22. |
- Unneberg, Per, 1974-
(författare)
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Computational approaches for in-depth analysis of cDNA sequence tags
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Major recent improvements in biotechnology have led to an accelerated production of DNA sequences. The completion of the human genome sequence, along with the genomes of more than two hundred other species, has marked the arrival of the genome era. The ultimate goal is to understand the structure and function of genomes and their genes. This thesis has focused on the computational analysis of complementary DNA (cDNA) sequences. These are copies of mRNA transcripts that correspond to the coding regions of genomes. Studying the expression patterns of genes is essential for understanding gene function. Many gene expression profiling techniques generate short sequence tags that derive from transcripts. A pilot study was performed to assess the feasibility of using the pyrosequencing platform for gene expression analysis. The sequences generated by pyrosequencing in most cases (≈ 85%) were long enough (> 18 nucleotides) to uniquely identify the corresponding transcripts through database searches. Aspects of transcript identification by short sequence tags were further investigated in a number of public databases, revealing that a tag length 16-17 nucleotides was sufficient for unique identifi- cation. Longer transcript representations are obtained from expressed sequence tag (EST) sequencing. Method development for the analysis and maintenance of large EST data sets has been performed on data from poplar, which is a tree of commercial interest to the forest biotechnology industry. In 2003 a large ESTsequencing project reached > 100 000 reads, providing a unique resource for tree biology research. ESTs have been grouped into clusters and singletons that represent potential genes. Preliminary analyses have estimated gene content in Populus to be very similar to that of model organism Arabidopsis thaliana. EST data collections provide a rich source for mining polymorphisms. A software application was developed and applied to EST data from two Populus species, and candidate single nucleotide polymorphisms (SNPs) were recorded. A study of genetic variation between the species revealed a striking similarity, with orthologous pairs being > 98% identical on the protein level. Keywords: cDNA, EST, gene expression, SNP, SAGE, polymorphism, assembly, clustering, DNA sequencing, pyrosequencing, mRNA transcript, orthology, tree biotechnology, restriction enzyme
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| 23. |
- Unneberg, Per, et al.
(författare)
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Ecological genomics in the Northern krill uncovers loci for local adaptation across ocean basins
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Krill are vital as food for many marine animals but also impacted by global warming. To learn how they and other zooplankton may adapt to a warmer world we studied local adaptation in the widespread Northern krill (Meganyctiphanes norvegica). We assemble and characterize its large genome and compare genome-scale variation among 74 specimens from the colder Atlantic Ocean and warmer Mediterranean Sea. The 19 Gb genome likely evolved through proliferation of retrotransposons, now targeted for inactivation by extensive DNA methylation, and contains many duplicated genes associated with molting and vision. Analysis of 760 million SNPs indicates extensive homogenizing gene-flow among populations. Nevertheless, we detect signatures of adaptive divergence across hundreds of genes, implicated in photoreception, circadian regulation, reproduction and thermal tolerance, indicating polygenic adaptation to light and temperature. The top gene candidate for ecological adaptation was nrf-6, a lipid transporter with a Mediterranean variant that may contribute to early spring reproduction. Such variation could become increasingly important for fitness in Atlantic stocks. Our study underscores the widespread but uneven distribution of adaptive variation, necessitating characterization of genetic variation among natural zooplankton populations to understand their adaptive potential, predict risks and support ocean conservation in the face of climate change.
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| 24. |
- Unneberg, Per, et al.
(författare)
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SNP discovery using advanced algorithms and neural networks
- 2005
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811 .- 1460-2059. ; 21:10, s. 2528-2530
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Tidskriftsartikel (refereegranskat)abstract
- Forage is an application which uses two neural networks for detecting single nucleotide polymorphisms (SNPs). Potential SNP candidates are identified in multiple alignments. Each candidate is then represented by a vector of features, which is classified as SNP or monomorphic by the networks. A validated dataset of SNPs was constructed from experimentally verified SNP data and used for network training and method evalutation.
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| 25. |
- Unneberg, Per, et al.
(författare)
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Transcript identification by analysis of short sequence tags-influence of tag length, restriction site and transcript database
- 2003
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 31:8, s. 2217-2226
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Tidskriftsartikel (refereegranskat)abstract
- There exist a number of gene expression profiling techniques that utilize restriction enzymes for generation of short expressed sequence tags. We have studied how the choice of restriction enzyme influences various characteristics of tags generated in an experiment. We have also investigated various aspects of in silico transcript identification that these profiling methods rely on. First, analysis of 14 248 mRNA sequences derived from the RefSeq transcript database showed that 1-30% of the sequences lack a given restriction enzyme recognition site. Moreover, 1-5% of the transcripts have recognition sites located less than 10 bases from the poly(A) tail. The uniqueness of 10 bp tags lies in the range 90-95%, which increases only slightly with longer tags, due to the existence of closely related transcripts. Furthermore, 3-30% of upstream 10 bp tags are identical to 3′ tags, introducing a risk of misclassification if upstream tags are present in a sample. Second, we found that a sequence length of 16-17 bp, including the recognition site, is sufficient for unique transcript identification by BLAST based sequence alignment to the UniGene Human non-redundant database. Third, we constructed a tag-to-gene mapping for UniGene and compared it to an existing mapping database. The mappings agreed to 79-83%, where the selection of representative sequences in the UniGene clusters is the main cause of the disagreement. The results of this study may serve to improve the interpretation of sequence-based expression studies and the design of hybridization arrays, by identifying short tags that have a high reliability and separating them from tags that carry an inherent ambiguity in their capacity to discriminate between genes. To this end, supplementary information in the form of a web companion to this paper is located at http://biobase.biotech.kth.se/tagseq.
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| 26. |
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| 27. |
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| 28. |
- Yazdi, Homa Papoli, et al.
(författare)
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The evolutionary maintenance of ancient recombining sex chromosomes in the ostrich
- 2023
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 19:6
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Tidskriftsartikel (refereegranskat)abstract
- Sex chromosomes have evolved repeatedly across the tree of life and often exhibit extreme size dimorphism due to genetic degeneration of the sex-limited chromosome (e.g. the W chromosome of some birds and Y chromosome of mammals). However, in some lineages, ancient sex-limited chromosomes have escaped degeneration. Here, we study the evolutionary maintenance of sex chromosomes in the ostrich (Struthio camelus), where the W remains 65% the size of the Z chromosome, despite being more than 100 million years old. Using genome-wide resequencing data, we show that the population scaled recombination rate of the pseudoautosomal region (PAR) is higher than similar sized autosomes and is correlated with pedigree-based recombination rate in the heterogametic females, but not homogametic males. Genetic variation within the sex-linked region (SLR) (& pi; = 0.001) was significantly lower than in the PAR, consistent with recombination cessation. Conversely, genetic variation across the PAR (& pi; = 0.0016) was similar to that of autosomes and dependent on local recombination rates, GC content and to a lesser extent, gene density. In particular, the region close to the SLR was as genetically diverse as autosomes, likely due to high recombination rates around the PAR boundary restricting genetic linkage with the SLR to only similar to 50Kb. The potential for alleles with antagonistic fitness effects in males and females to drive chromosome degeneration is therefore limited. While some regions of the PAR had divergent male-female allele frequencies, suggestive of sexually antagonistic alleles, coalescent simulations showed this was broadly consistent with neutral genetic processes. Our results indicate that the degeneration of the large and ancient sex chromosomes of the ostrich may have been slowed by high recombination in the female PAR, reducing the scope for the accumulation of sexually antagonistic variation to generate selection for recombination cessation.
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