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Johansson, Anna C. V.
Alternative names
Publications (8 of 8) Show all publications
Shebanits, K., Günther, T., Johansson, A. C. V., Maqbool, K., Feuk, L., Jakobsson, M. & Larhammar, D. (2019). Copy number determination of the gene for the human pancreatic polypeptide receptor NPY4R using read depth analysis and droplet digital PCR.. BMC Biotechnology, 19, Article ID 31.
Open this publication in new window or tab >>Copy number determination of the gene for the human pancreatic polypeptide receptor NPY4R using read depth analysis and droplet digital PCR.
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2019 (English)In: BMC Biotechnology, ISSN 1472-6750, E-ISSN 1472-6750, Vol. 19, article id 31Article in journal (Refereed) Published
Abstract [en]

Background: Copy number variation (CNV) plays an important role in human genetic diversity and has been associated with multiple complex disorders. Here we investigate a CNV on chromosome 10q11.22 that spans NPY4R, the gene for the appetite-regulating pancreatic polypeptide receptor Y4. This genomic region has been challenging to map due to multiple repeated elements and its precise organization has not yet been resolved. Previous studies using microarrays were interpreted to show that the most common copy number was 2 per genome.

Results: We have investigated 18 individuals from the 1000 Genomes project using the well-established method of read depth analysis and the new droplet digital PCR (ddPCR) method. We find that the most common copy number for NPY4R is 4. The estimated number of copies ranged from three to seven based on read depth analyses with Control-FREEC and CNVnator, and from four to seven based on ddPCR. We suggest that the difference between our results and those published previously can be explained by methodological differences such as reference gene choice, data normalization and method reliability. Three high-quality archaic human genomes (two Neanderthal and one Denisova) display four copies of the NPY4R gene indicating that a duplication occurred prior to the human-Neanderthal/Denisova split.

Conclusions: We conclude that ddPCR is a sensitive and reliable method for CNV determination, that it can be used for read depth calibration in CNV studies based on already available whole-genome sequencing data, and that further investigation of NPY4R copy number variation and its consequences are necessary due to the role of Y4 receptor in food intake regulation.

National Category
Cell Biology Genetics
Identifiers
urn:nbn:se:uu:diva-356569 (URN)10.1186/s12896-019-0523-9 (DOI)000470281900001 ()31164119 (PubMedID)
Funder
Swedish Research CouncilThe Swedish Brain Foundation
Available from: 2018-08-01 Created: 2018-08-01 Last updated: 2019-06-25Bibliographically approved
Wang, J., Ding, J., Tan, B., Robinson, K. M., Michelson, I. H., Johansson, A., . . . Ingvarsson, P. K. (2018). A major locus controls local adaptation and adaptive life history variation in a perennial plant. Genome Biology, 19, Article ID 72.
Open this publication in new window or tab >>A major locus controls local adaptation and adaptive life history variation in a perennial plant
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2018 (English)In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 19, article id 72Article in journal (Refereed) Published
National Category
Genetics
Identifiers
urn:nbn:se:uu:diva-357691 (URN)10.1186/s13059-018-1444-y (DOI)000434210500001 ()29866176 (PubMedID)
Available from: 2018-06-04 Created: 2018-08-22 Last updated: 2018-08-25Bibliographically approved
Lin, Y.-C., Wang, J., Delhomme, N., Schiffthaler, B., Sundström, G., Zuccolo, A., . . . Street, N. R. (2018). Functional and evolutionary genomic inferences in Populus through genome and population sequencing of American and European aspen. Proceedings of the National Academy of Sciences of the United States of America, 115(46), E10970-E10978
Open this publication in new window or tab >>Functional and evolutionary genomic inferences in Populus through genome and population sequencing of American and European aspen
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2018 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 115, no 46, p. E10970-E10978Article in journal (Refereed) Published
National Category
Bioinformatics and Systems Biology
Identifiers
urn:nbn:se:uu:diva-366971 (URN)10.1073/pnas.1801437115 (DOI)000449934400020 ()30373829 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationSwedish Foundation for Strategic Research Swedish Research CouncilEU, FP7, Seventh Framework Programme, 322739-DOUBLEUP
Available from: 2018-11-13 Created: 2018-11-27 Last updated: 2019-06-26Bibliographically approved
Franco, I., Johansson, A. C. V., Olsson, K., Vrtacnik, P., Lundin, P., Helgadottir, H. T., . . . Eriksson, M. (2018). Somatic mutagenesis in satellite cells associates with human skeletal muscle aging. Nature Communications, 9, Article ID 800.
Open this publication in new window or tab >>Somatic mutagenesis in satellite cells associates with human skeletal muscle aging
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2018 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, article id 800Article in journal (Refereed) Published
Abstract [en]

Human aging is associated with a decline in skeletal muscle (SkM) function and a reduction in the number and activity of satellite cells (SCs), the resident stem cells. To study the connection between SC aging and muscle impairment, we analyze the whole genome of single SC clones of the leg muscle vastus lateralis from healthy individuals of different ages (21-78 years). We find an accumulation rate of 13 somatic mutations per genome per year, consistent with proliferation of SCs in the healthy adult muscle. SkM-expressed genes are protected from mutations, but aging results in an increase in mutations in exons and promoters, targeting genes involved in SC activity and muscle function. In agreement with SC mutations affecting the whole tissue, we detect a missense mutation in a SC propagating to the muscle. Our results suggest somatic mutagenesis in SCs as a driving force in the age-related decline of SkM function.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2018
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-348850 (URN)10.1038/s41467-018-03244-6 (DOI)000425935100013 ()29476074 (PubMedID)
Funder
Swedish Research CouncilSwedish Society of MedicineMarianne and Marcus Wallenberg FoundationKnut and Alice Wallenberg FoundationWallenberg FoundationsScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Available from: 2018-04-18 Created: 2018-04-18 Last updated: 2018-04-18Bibliographically approved
Lindqvist, C. M., Nordlund, J., Ekman, D., Johansson, A., Moghadam, B. T., Raine, A., . . . Berglund, E. C. (2015). The Mutational Landscape in Pediatric Acute Lymphoblastic Leukemia Deciphered by Whole Genome Sequencing. Human Mutation, 36(1), 118-128
Open this publication in new window or tab >>The Mutational Landscape in Pediatric Acute Lymphoblastic Leukemia Deciphered by Whole Genome Sequencing
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2015 (English)In: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 36, no 1, p. 118-128Article in journal (Refereed) Published
Abstract [en]

Genomic characterization of pediatric acute lymphoblastic leukemia (ALL) has identified distinct patterns of genes and pathways altered in patients with well-defined genetic aberrations. To extend the spectrum of known somatic variants in ALL, we performed whole genome and transcriptome sequencing of three B-cell precursor patients, of which one carried the t(12;21)ETV6-RUNX1 translocation and two lacked a known primary genetic aberration, and one T-ALL patient. We found that each patient had a unique genome, with a combination of well-known and previously undetected genomic aberrations. By targeted sequencing in 168 patients, we identified KMT2D and KIF1B as novel putative driver genes. We also identified a putative regulatory non-coding variant that coincided with overexpression of the growth factor MDK. Our results contribute to an increased understanding of the biological mechanisms that lead to ALL and suggest that regulatory variants may be more important for cancer development than recognized to date. The heterogeneity of the genetic aberrations in ALL renders whole genome sequencing particularly well suited for analysis of somatic variants in both research and diagnostic applications.

National Category
Medical Genetics Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-238183 (URN)10.1002/humu.22719 (DOI)000347076700016 ()25355294 (PubMedID)
Available from: 2014-12-10 Created: 2014-12-10 Last updated: 2018-01-11Bibliographically approved
Klar, J., Sobol, M., Melberg, A., Mäbert, K., Ameur, A., Johansson, A. C., . . . Dahl, N. (2013). Welander Distal Myopathy Caused by an Ancient Founder Mutation in TIA1 Associated with Perturbed Splicing.. Human Mutation, 34(4), 572-577
Open this publication in new window or tab >>Welander Distal Myopathy Caused by an Ancient Founder Mutation in TIA1 Associated with Perturbed Splicing.
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2013 (English)In: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 34, no 4, p. 572-577Article in journal (Refereed) Published
Abstract [en]

Welander distal myopathy (WDM) is an adult onset autosomal dominant disorder characterized by distal limb weakness which progresses slowly from the fifth decade. All WDM patients are of Swedish or Finnish descent and share a rare chromosome 2p13 haplotype. We restricted the WDM associated haplotype followed by whole exome sequencing. Within the conserved haplotype we identified a single heterozygous mutation c.1150G>A (p.E384K) in TIA1 in all WDM patients investigated (n = 43). The TIA1 protein regulates splicing and translation through direct interaction with mRNA and the p.E384K mutation is located in the C-terminal Q-rich domain that interacts with the U1-C splicing factor. TIA1 has been shown to prevent skipping of SMN2 exon 7 and we show that WDM patients have increased levels of spliced SMN2 in skeletal muscle cells when compared to controls. Immunostaining of WDM muscle biopsies showed accumulation of TIA1 and stress granulae proteins adjacent to intracellular inclusions, a typical finding in WDM. The combined findings strongly suggest that the TIA1 mutation causes perturbed RNA splicing and cellular stress resulting in WDM. The selection against the mutation is likely to be negligible and the age of the TIA1 founder mutation was calculated to approximately 1050 years, which coincides with the epoch of early seafaring across the Baltic Sea.

National Category
Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:uu:diva-197333 (URN)10.1002/humu.22282 (DOI)000316629000005 ()23348830 (PubMedID)
Available from: 2013-03-22 Created: 2013-03-22 Last updated: 2017-12-06Bibliographically approved
Ameur, A., Enroth, S., Johansson, Å., Zaboli, G., Igl, W., Johansson, A. C. V., . . . Gyllensten, U. (2012). Genetic Adaptation of Fatty-Acid Metabolism: A Human-Specific Haplotype Increasing the Biosynthesis of Long-Chain Omega-3 and Omega-6 Fatty Acids. American Journal of Human Genetics, 90(5), 809-820
Open this publication in new window or tab >>Genetic Adaptation of Fatty-Acid Metabolism: A Human-Specific Haplotype Increasing the Biosynthesis of Long-Chain Omega-3 and Omega-6 Fatty Acids
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2012 (English)In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 90, no 5, p. 809-820Article in journal (Refereed) Published
Abstract [en]

Omega-3 and omega-6 long-chain polyunsaturated fatty acids (LC-PUFAs) are essential for the development and function of the human brain. They can be obtained directly from food, e.g., fish, or synthesized from precursor molecules found in vegetable oils. To determine the importance of genetic variability to fatty-acid biosynthesis, we studied FADS1 and FADS2, which encode rate-limiting enzymes for fatty-acid conversion. We performed genome-wide genotyping (n = 5,652 individuals) and targeted resequencing (n = 960 individuals) of the FADS region in five European population cohorts. We also analyzed available genomic data from human populations, archaic hominins, and more distant primates. Our results show that present-day humans have two common FADS haplotypes-defined by 28 closely linked SNPs across 38.9 kb-that differ dramatically in their ability to generate LC-PUFAs. No independent effects on FADS activity were seen for rare SNPs detected by targeted resequencing. The more efficient, evolutionarily derived haplotype appeared after the lineage split leading to modern humans and Neanderthals and shows evidence of positive selection. This human-specific haplotype increases the efficiency of synthesizing essential long-chain fatty acids from precursors and thereby might have provided an advantage in environments with limited access to dietary LC-PUFAs. In the modern world, this haplotype has been associated with lifestyle-related diseases, such as coronary artery disease.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-175197 (URN)10.1016/j.ajhg.2012.03.014 (DOI)000303907500005 ()
Available from: 2012-06-07 Created: 2012-06-04 Last updated: 2018-07-06Bibliographically approved
Hooper, S. D., Johansson, A. C. V., Tellgren-Roth, C., Stattin, E.-L., Dahl, N., Cavelier, L. & Feuk, L. (2012). Genome-wide sequencing for the identification of rearrangements associated with Tourette syndrome and obsessive-compulsive disorder. BMC Medical Genetics, 13, 123
Open this publication in new window or tab >>Genome-wide sequencing for the identification of rearrangements associated with Tourette syndrome and obsessive-compulsive disorder
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2012 (English)In: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 13, p. 123-Article in journal (Refereed) Published
Abstract [en]

Background: Tourette Syndrome (TS) is a neuropsychiatric disorder in children characterized by motor and verbal tics. Although several genes have been suggested in the etiology of TS, the genetic mechanisms remain poorly understood. Methods: Using cytogenetics and FISH analysis, we identified an apparently balanced t(6,22)(q16.2;p13) in a male patient with TS and obsessive-compulsive disorder (OCD). In order to map the breakpoints and to identify additional submicroscopic rearrangements, we performed whole genome mate-pair sequencing and CGH-array analysis on DNA from the proband. Results: Sequence and CGH array analysis revealed a 400 kb deletion located 1.3 Mb telomeric of the chromosome 6q breakpoint, which has not been reported in controls. The deletion affects three genes (GPR63, NDUFA4 and KLHL32) and overlaps a region previously found deleted in a girl with autistic features and speech delay. The proband's mother, also a carrier of the translocation, was diagnosed with OCD and shares the deletion. We also describe a further potentially related rearrangement which, while unmapped in Homo sapiens, was consistent with the chimpanzee genome. Conclusions: We conclude that genome-wide sequencing at relatively low resolution can be used for the identification of submicroscopic rearrangements. We also show that large rearrangements may escape detection using standard analysis of whole genome sequencing data. Our findings further provide a candidate region for TS and OCD on chromosome 6q16.

Keywords
Tourette syndrome, Paired end sequencing, Chromosomal translocation, Structural variations
National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-195631 (URN)10.1186/1471-2350-13-123 (DOI)000314114000001 ()
Available from: 2013-02-27 Created: 2013-02-26 Last updated: 2017-12-06Bibliographically approved
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