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- Kaasinen, E, et al.
(författare)
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Impact of constitutional TET2 haploinsufficiency on molecular and clinical phenotype in humans
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1252-
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Tidskriftsartikel (refereegranskat)abstract
- Clonal hematopoiesis driven by somatic heterozygous TET2 loss is linked to malignant degeneration via consequent aberrant DNA methylation, and possibly to cardiovascular disease via increased cytokine and chemokine expression as reported in mice. Here, we discover a germline TET2 mutation in a lymphoma family. We observe neither unusual predisposition to atherosclerosis nor abnormal pro-inflammatory cytokine or chemokine expression. The latter finding is confirmed in cells from three additional unrelated TET2 germline mutation carriers. The TET2 defect elevates blood DNA methylation levels, especially at active enhancers and cell-type specific regulatory regions with binding sequences of master transcription factors involved in hematopoiesis. The regions display reduced methylation relative to all open chromatin regions in four DNMT3A germline mutation carriers, potentially due to TET2-mediated oxidation. Our findings provide insight into the interplay between epigenetic modulators and transcription factor activity in hematological neoplasia, but do not confirm the putative role of TET2 in atherosclerosis.
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| 6. |
- Kuisma, H, et al.
(författare)
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Parity associates with chromosomal damage in uterine leiomyomas
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 5448-
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Tidskriftsartikel (refereegranskat)abstract
- Mechanical forces in a constrained cellular environment were recently established as a facilitator of chromosomal damage. Whether this could contribute to tumorigenesis is not known. Uterine leiomyomas are common neoplasms that display relatively few chromosomal aberrations. We hypothesized that if mechanical forces contribute to chromosomal damage, signs of this could be seen in uterine leiomyomas from parous women. We examined the karyotypes of 1946 tumors, and found a striking overrepresentation of chromosomal damage associated with parity. We then subjected myometrial cells to physiological forces similar to those encountered during pregnancy, and found this to cause DNA breaks and a DNA repair response. While mechanical forces acting in constrained cellular environments may thus contribute to neoplastic degeneration, and genesis of uterine leiomyoma, further studies are needed to prove possible causality of the observed association. No evidence for progression to malignancy was found.
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| 7. |
- Ojala, A. E. K., et al.
(författare)
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Ice-sheet scale distribution and morphometry of triangular-shaped hummocks (murtoos): a subglacial landform produced during rapid retreat of the Scandinavian Ice Sheet
- 2019
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Ingår i: Annals of Glaciology. - : Cambridge University Press (CUP). - 0260-3055 .- 1727-5644. ; 60:80, s. 115-126
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Tidskriftsartikel (refereegranskat)abstract
- High-resolution digital elevation models of Finland and Sweden based on LiDAR (Light Detection and Ranging) reveal subglacial landforms in great detail. We describe the ice-sheet scale distribution and morphometric characteristics of a glacial landform that is distinctive in morphology and occurs commonly in the central parts of the former Scandinavian Ice Sheet, especially up-ice of the Younger Dryas end moraine zone. We refer to these triangular or V-shaped landforms as murtoos (singular, `murtoo'). Murtoos are typically 30-200 m in length and 30-200 m in width with a relief of commonly <5 m. Murtoos have straight and steep edges, a triangular tip oriented parallel to ice-flow direction, and an asymmetric longitudinal profile with a shorter, but steeper down-ice slope. The spatial distribution of murtoos and their geomorphic relation to other landforms indicate that they formed subglacially during times of climate warming and rapid retreat of the Scandinavian Ice Sheet when large amounts of meltwater were delivered to the bed. Murtoos are formed under warm-based ice and may be associated with a non-channelized subglacial hydraulic system that evacuated large discharges of subglacial water.
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| 9. |
- Ahola, Virpi, et al.
(författare)
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The Glanville fritillary genome retains an ancient karyotype and reveals selective chromosomal fusions in Lepidoptera
- 2014
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 4737-
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have reported that chromosome synteny in Lepidoptera has been well conserved, yet the number of haploid chromosomes varies widely from 5 to 223. Here we report the genome (393 Mb) of the Glanville fritillary butterfly (Melitaea cinxia; Nymphalidae), a widely recognized model species in metapopulation biology and eco-evolutionary research, which has the putative ancestral karyotype of n = 31. Using a phylogenetic analyses of Nymphalidae and of other Lepidoptera, combined with orthologue-level comparisons of chromosomes, we conclude that the ancestral lepidopteran karyotype has been n = 31 for at least 140 My. We show that fusion chromosomes have retained the ancestral chromosome segments and very few rearrangements have occurred across the fusion sites. The same, shortest ancestral chromosomes have independently participated in fusion events in species with smaller karyotypes. The short chromosomes have higher rearrangement rate than long ones. These characteristics highlight distinctive features of the evolutionary dynamics of butterflies and moths.
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