| 31. |
- Margaryan, Ashot, et al.
(författare)
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Population genomics of the Viking world
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 585:7825, s. 390-396
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Tidskriftsartikel (refereegranskat)abstract
- The maritime expansion of Scandinavian populations during the Viking Age (about ad750–1050) was a far-flung transformation in world history1,2. Here we sequenced the genomes of 442humans from archaeological sites across Europe and Greenland (to a median depth of about 1×) to understand the global influence of this expansion. We find the Viking period involved gene flow into Scandinavia from the south and east. We observe genetic structure within Scandinavia, with diversity hotspots in the south and restricted gene flow within Scandinavia. We find evidence for a major influx of Danish ancestry into England; a Swedish influx into the Baltic; and Norwegian influx into Ireland, Iceland and Greenland. Additionally, we see substantial ancestry from elsewhere in Europe entering Scandinavia during the Viking Age. Our ancient DNA analysis also revealed that a Viking expedition included close family members. By comparing with modern populations, we find that pigmentation-associated loci have undergone strong population differentiation during the past millennium, and trace positively selected loci—including the lactase-persistence allele of LCT and alleles of ANKA that are associated with the immune response—in detail. We conclude that the Viking diaspora was characterized by substantial transregional engagement: distinct populations influenced the genomic makeup of different regions of Europe, and Scandinavia experienced increased contact with the rest of the continent.
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| 32. |
- Margolis, Russell L, et al.
(författare)
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Huntington's Disease-like 2 (HDL2) in North America and Japan.
- 2004
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 56:5, s. 670-4
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Tidskriftsartikel (refereegranskat)abstract
- Huntington's Disease-like 2 (HDL2) is a progressive, autosomal dominant, neurodegenerative disorder with marked clinical and pathological similarities to Huntington's disease (HD). The causal mutation is a CTG/CAG expansion mutation on chromosome 16q24.3, in a variably spliced exon of junctophilin-3. The frequency of HDL2 was determined in nine independent series of patients referred for HD testing or selected for the presence of an HD-like phenotype in North America or Japan. The repeat length, ancestry, and age of onset of all North American HDL2 cases were determined. The results show that HDL2 is very rare, with a frequency of 0 to 15% among patients in the nine case series with an HD-like presentation who do not have the HD mutation. HDL2 is predominantly, and perhaps exclusively, found in individuals of African ancestry. Repeat expansions ranged from 44 to 57 triplets, with length instability in maternal transmission detected in a repeat of r2=0.29, p=0.0098). The results further support the evidence that the repeat expansion at the chromosome 16q24.3 locus is the direct cause of HDL2 and provide preliminary guidelines for the genetic testing of patients with an HD-like phenotype.
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| 33. |
- Osorio, Ana, et al.
(författare)
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DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
- 2014
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7×10-3) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8×10-3). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
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| 34. |
- Rasmussen, Jay, et al.
(författare)
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Amyloid polymorphisms constitute distinct clouds of conformational variants in different etiological subtypes of Alzheimers disease
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 114:49, s. 13018-13023
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Tidskriftsartikel (refereegranskat)abstract
- The molecular architecture of amyloids formed in vivo can be interrogated using luminescent conjugated oligothiophenes (LCOs), a unique class of amyloid dyes. When bound to amyloid, LCOs yield fluorescence emission spectra that reflect the 3D structure of the protein aggregates. Given that synthetic amyloid-beta peptide (A beta) has been shown to adopt distinct structural conformations with different biological activities, we asked whether A beta can assume structurally and functionally distinct conformations within the brain. To this end, we analyzed the LCO-stained cores of beta-amyloid plaques in postmortem tissue sections from frontal, temporal, and occipital neocortices in 40 cases of familial Alzheimers disease (AD) or sporadic (idiopathic) AD (sAD). The spectral attributes of LCO-bound plaques varied markedly in the brain, but the mean spectral properties of the amyloid cores were generally similar in all three cortical regions of individual patients. Remarkably, the LCO amyloid spectra differed significantly among some of the familial and sAD subtypes, and between typical patients with sAD and those with posterior cortical atrophy AD. Neither the amount of A beta nor its protease resistance correlated with LCO spectral properties. LCO spectral amyloid phenotypes could be partially conveyed to A beta plaques induced by experimental transmission in a mouse model. These findings indicate that polymorphic A beta-amyloid deposits within the brain cluster as clouds of conformational variants in different AD cases. Heterogeneity in the molecular architecture of pathogenic A beta among individuals and in etiologically distinct subtypes of AD justifies further studies to assess putative links between A beta conformation and clinical phenotype.
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| 35. |
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| 36. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 37. |
- Vanhala, Lisa, et al.
(författare)
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Reflections on the Global Governance of Climate Change Loss and Damage at COP26.
- 2021
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Annan publikation (populärvet., debatt m.m.)abstract
- What happened on the issue of loss and damage atthe 26th Conference of the Parties (COP26) held inGlasgow in November 2021 and why does it matter?In many ways COP26 was the moment when lossand damage was transformed from being an issueof importance to certain states and communities –for example the small island states – to one that hasbecome centre stage for much of the world. Thedeveloping countries grouping, known as the G77plus China, were united in unprecedented ways onthe issue of loss and damage in Glasgow. We alsowitnessed a host of different non-state and substate stakeholders taking up the mantle of loss anddamage from those marching in the streets, to theFirst Minister of Scotland to the Trade Unionconstituency of the UNFCCC.Given the growing frequency and intensity of theadverse impacts of climate change globally and thelaunch of the most recent assessment of theIntergovernmental Panel on Climate Change(IPCC), the Working Group I contribution to the 6thAssessment Report, this is an issue that is now onthe political agenda. This set of short reflectionsfrom our inter-disciplinary team of expertsadvances our understanding of the globalgovernance of climate change loss and damage.Coming from different disciplinary perspectives,from anthropology and law to geography andpolitical science, we explore the topic of climatechange loss and damage governance focusing onissues of finance, science and expertise, policy, lawand litigation.
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| 38. |
- Wagner, Jessica, et al.
(författare)
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Medin co-aggregates with vascular amyloid-beta in Alzheimers disease
- 2022
-
Ingår i: Nature. - : Nature Portfolio. - 0028-0836 .- 1476-4687. ; 612, s. 123-131
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Tidskriftsartikel (refereegranskat)abstract
- Aggregates of medin amyloid (a fragment of the protein MFG-E8, also known as lactadherin) are found in the vasculature of almost all humans over 50 years of age(1,)(2), making it the most common amyloid currently known. We recently reported that medin also aggregates in blood vessels of ageing wild-type mice, causing cerebrovascular dysfunction(3). Here we demonstrate in amyloid-beta precursor protein (APP) transgenic mice and in patients with Alzheimers disease that medin co-localizes with vascular amyloid-beta deposits, and that in mice, medin deficiency reduces vascular amyloid-beta deposition by half. Moreover, in both the mouse and human brain, MFG-E8 is highly enriched in the vasculature and both MFG-E8 and medin levels increase with the severity of vascular amyloid-beta burden. Additionally, analysing data from 566 individuals in the ROSMAP cohort, we find that patients with Alzheimers disease have higher MFGE8 expression levels, which are attributable to vascular cells and are associated with increased measures of cognitive decline, independent of plaque and tau pathology. Mechanistically, we demonstrate that medin interacts directly with amyloid-beta to promote its aggregation, as medin forms heterologous fibrils with amyloid-beta, affects amyloid-beta fibril structure, and cross-seeds amyloid-beta aggregation both in vitro and in vivo. Thus, medin could be a therapeutic target for prevention of vascular damage and cognitive decline resulting from amyloid-beta deposition in the blood vessels of the brain.
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| 39. |
- Walker, Donald A., et al.
(författare)
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Vegetation on mesic loamy and sandy soils along a 1700-km maritime Eurasia Arctic Transect
- 2019
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Ingår i: Applied Vegetation Science. - : John Wiley & Sons. - 1402-2001 .- 1654-109X. ; 22:1, s. 150-167
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Tidskriftsartikel (refereegranskat)abstract
- Questions: How do plant communities on zonal loamy vs. sandy soils vary across the full maritime Arctic bioclimate gradient? How are plant communities of these areas related to existing vegetation units of the European Vegetation Classification? What are the main environmental factors controlling transitions of vegetation along the bioclimate gradient?Location: 1700-km Eurasia Arctic Transect (EAT), Yamal Peninsula and Franz Josef Land (FJL), Russia.Methods: The Braun-Blanquet approach was used to sample mesic loamy and sandy plots on 14 total study sites at six locations, one in each of the five Arctic bioclimate subzones and the forest-tundra transition. Trends in soil factors, cover of plant growth forms (PGFs) and species diversity were examined along the summer warmth index (SWI) gradient and on loamy and sandy soils. Classification and ordination were used to group the plots and to test relationships between vegetation and environmental factors.Results: Clear, mostly non-linear, trends occurred for soil factors, vegetation structure and species diversity along the climate gradient. Cluster analysis revealed seven groups with clear relationships to subzone and soil texture. Clusters at the ends of the bioclimate gradient (forest-tundra and polar desert) had many highly diagnostic taxa, whereas clusters from the Yamal Peninsula had only a few. Axis 1 of a DCA was strongly correlated with latitude and summer warmth; Axis 2 was strongly correlated with soil moisture, percentage sand and landscape age.Conclusions: Summer temperature and soil texture have clear effects on tundra canopy structure and species composition, with consequences for ecosystem properties. Each layer of the plant canopy has a distinct region of peak abundance along the bioclimate gradient. The major vegetation types are weakly aligned with described classes of the European Vegetation Checklist, indicating a continuous floristic gradient rather than distinct subzone regions. The study provides ground-based vegetation data for satellite-based interpretations of the western maritime Eurasian Arctic, and the first vegetation data from Hayes Island, Franz Josef Land, which is strongly separated geographically and floristically from the rest of the gradient and most susceptible to on-going climate change.
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| 40. |
- Walker, Thomas, et al.
(författare)
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Ankyrin repeat domain-encoding genes in the wPip strain of Wolbachia from the Culex pipiens group.
- 2007
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Ingår i: BMC Biology. - : Springer Science and Business Media LLC. - 1741-7007. ; 5, s. 39-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Wolbachia are obligate endosymbiotic bacteria maternally transmitted through the egg cytoplasm that are responsible for several reproductive disorders in their insect hosts, such as cytoplasmic incompatibility (CI) in infected mosquitoes. Species in the Culex pipiens complex display an unusually high number of Wolbachia-induced crossing types, and based on present data, only the wPip strain is present.RESULTS: The sequencing of the wPip strain of Wolbachia revealed the presence of 60 ankyrin repeat domain (ANK) encoding genes and expression studies of these genes were carried out in adult mosquitoes. One of these ANK genes, pk2, is shown to be part of an operon of three prophage-associated genes with sex-specific expression, and is present in two identical copies in the genome. Another homolog of pk2 is also present that is differentially expressed in different Cx. pipiens group strains. A further two ANK genes showed sex-specific regulation in wPip-infected Cx. pipiens group adults.CONCLUSION: The high number, variability and differential expression of ANK genes in wPip suggest an important role in Wolbachia biology, and the gene family provides both markers and promising candidates for the study of reproductive manipulation.
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