| 1. |
- Martin, Alicia R, et al.
(författare)
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Haplotype Sharing Provides Insights into Fine-Scale Population History and Disease in Finland
- 2018
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 102:5, s. 760-775
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Tidskriftsartikel (refereegranskat)abstract
- Finland provides unique opportunities to investigate population and medical genomics because of its adoption of unified national electronic health records, detailed historical and birth records, and serial population bottlenecks. We assembled a comprehensive view of recent population history (≤100 generations), the timespan during which most rare-disease-causing alleles arose, by comparing pairwise haplotype sharing from 43,254 Finns to that of 16,060 Swedes, Estonians, Russians, and Hungarians from geographically and linguistically adjacent countries with different population histories. We find much more extensive sharing in Finns, with at least one ≥ 5 cM tract on average between pairs of unrelated individuals. By coupling haplotype sharing with fine-scale birth records from more than 25,000 individuals, we find that although haplotype sharing broadly decays with geographical distance, there are pockets of excess haplotype sharing; individuals from northeast Finland typically share several-fold more of their genome in identity-by-descent segments than individuals from southwest regions. We estimate recent effective population-size changes through time across regions of Finland, and we find that there was more continuous gene flow as Finns migrated from southwest to northeast between the early- and late-settlement regions than was dichotomously described previously. Lastly, we show that haplotype sharing is locally enriched by an order of magnitude among pairs of individuals sharing rare alleles and especially among pairs sharing rare disease-causing variants. Our work provides a general framework for using haplotype sharing to reconstruct an integrative view of recent population history and gain insight into the evolutionary origins of rare variants contributing to disease.
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| 2. |
- Pirinen, Pekka, et al.
(författare)
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Wireless Connectivity for Remote and Arctic Areas – Food for Thought
- 2019
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Ingår i: ISWCS 2019. - : IEEE. ; , s. 43-47
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This paper addresses various aspects that should be considered to improve the digital inclusion of remote, and specifically arctic areas, so that the geographical location would play a lesser role in equality among the people. To this end, technological challenges and potential solutions are discussed. They are further elaborated by three examples that have different architectural use case specific challenges for remote area wireless connectivity. The active role of society is seen pivotal alongside with the technological solutions to make this happen.
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| 3. |
- Popovski, Petar, et al.
(författare)
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EU FP7 INFSO-ICT-317669 METIS, D2.1, Requirement analysis and design approaches for 5G air interface
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This document describes the problem space for the METIS research conducted in the radio link context. Firstly, a requirement analysis for the air interface design is conducted based on the test case descriptions presented in METIS deliverable D1.1. It follows an introduction of the research topics being pursued in the radio link research together with an illustration of how these topics are addressing the derived requirements. Moreover, it is shown which of thoserequirements address the needs of the METIS horizontal topics. To facilitate the achievement of these three objectives, a framework of General Requirements is introduced, which will be used throughout the project to assess and evaluate developed radio link solutions and to allow for measuring against the overall system performance goals.
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| 4. |
- Popovski, Petar, et al.
(författare)
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EU FP7 INFSO-ICT-317669 METIS, D2.2 Novel radio link concepts and state of the art analysis
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This document provides a detailed overview of the Radio Link concepts being developed in METIS as well as a detailed analysis of the related state of the art. For each of the research topics identified for the radio link research covering flexible air interface, new waveforms,modulation and coding techniques as well as multiple access, medium access control and enablers for radio resource management, a detailed description of the aspects to be investigated will be given, going beyond the limits imposed by the systems operated today and their planned evolutions. The state of the art analysis, which is conducted for each of the research topics separately, covers current standards, their future evolutions as well as latest academic research. Elaborating on how the approaches followed in the radio link research may advance this state of the art carves a promising track towards innovative solutions addressing the challenges of future wireless communication.
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| 5. |
- Popovski, Petar, et al.
(författare)
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EU FP7 INFSO-ICT-317669 METIS, D2.3 Components of a new air interface - building blocks and performance
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This document provides intermediate results of the concepts being developed in the radio link research of METIS. For each of the technology components (TeC) within the technology component clusters (TeCC), covering flexible air interface, new waveforms, modulation and coding techniques as well as multiple access, medium access control and enablers for radio resource management, key findings and conclusions collected so far are summarized in section 2. Continuative descriptions and research outcomes are given in the annex and referred publications.The results presented here will be extended in the further progress of the project, and they will be used in the next phase of the project to develop and refine the overall METIS system concept instantiated by the horizontal topics. The suitability of the single technology components for the overall system design being able to meet the wide range of requirements for 5G will then be evaluated.
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| 6. |
- Popovski, Petar, et al.
(författare)
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EU FP7 INFSO-ICT-317669 METIS, D2.4 Proposed solutions for new radio access
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This deliverable represents the final report on the METIS radio link research. It provides a comprehensive and self-contained summary of all investigated technology components (TeCs), including evaluation results and conclusions on their potential for 5G. The METIS radio link research covers three main areas, which are considered key aspects for developing a self-contained air interface design for 5G: 1) Flexible air interface, 2) Waveforms, coding & modulation and transceiver design and 3) Multiple access, Medium Access Control (MAC) and Radio Resource Management (RRM). TeCs with similar research context and objectives have been grouped into clusters, whereof five have been selected as the most promising for 5G systems: From research area 1, TeC clusters providing key enablers for an air interface for ultra-dense networks (UDN) and for moving networks; from research area 2, multi-carrier transmission schemes with filtering; and from research area 3, novel access schemes for massive machine access as well as for non-orthogonal access.
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| 7. |
- Purhonen, Janne, et al.
(författare)
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NAD+ repletion produces no therapeutic effect in mice with respiratory chain complex III deficiency and chronic energy deprivation
- 2018
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Ingår i: FASEB Journal. - 0892-6638. ; 32:11, s. 5913-5926
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Tidskriftsartikel (refereegranskat)abstract
- Biosynthetic precursors of NAD+ can replenish a decreased cellular NAD+ pool and, supposedly via sirtuin (SIRT) deacetylases, improvemitochondrial function.Wefound decreased hepaticNAD+ concentration and downregulated biosynthesis in Bcs1lp.S78G knock-in mice with respiratory chain complex III deficiency and mitochondrial hepatopathy. Aiming at ameliorating disease progression via NAD+ repletion and improved mitochondrial function, we fed thesemice nicotinamide riboside (NR), aNAD+ precursor. A targetedmetabolomics verified successful administration and suggested enhancedNAD+ biosynthesis in the treated mice, although hepaticNAD+ concentrationwas unchanged at the end point. In contrast to our expectations,NRdid not improve the hepatopathy, hepatic mitochondrial respiration, or survival of Bcs1lp.S78G mice. We linked this lack of therapeutic effect to NAD+-independent activation of SIRT-1 and -3 via AMPK and cAMP signaling related to the starvation-like metabolic state of Bcs1lp.S78G mice. In summary, we describe an unusual metabolic state with NAD+ depletion accompanied by energy deprivation signals, uncompromised SIRT function, and upregulated oxidative metabolism. Our study highlights that the knowledge of the underlying complexmetabolic alterations is criticalwhen designing therapies formitochondrial dysfunction.
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| 8. |
- Surakka, Ida, et al.
(författare)
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The impact of low-frequency and rare variants on lipid levels.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:6, s. 589-597
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Tidskriftsartikel (refereegranskat)abstract
- Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, we identify association to lipid traits in 93 loci, including 79 previously identified loci with new lead SNPs and 10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense lead SNP, and 2 loci with an accumulation of rare variants. In six loci, SNPs with established function in lipid genetics (CELSR2, GCKR, LIPC and APOE) or candidate missense mutations with predicted damaging function (CD300LG and TM6SF2) explained the locus associations. The low-frequency variants increased the proportion of variance explained, particularly for low-density lipoprotein cholesterol and total cholesterol. Altogether, our results highlight the impact of low-frequency variants in complex traits and show that imputation offers a cost-effective alternative to resequencing.
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| 9. |
- Tukiainen, Taru, et al.
(författare)
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Chromosome x-wide association study identifies Loci for fasting insulin and height and evidence for incomplete dosage compensation.
- 2014
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- The X chromosome (chrX) represents one potential source for the "missing heritability" for complex phenotypes, which thus far has remained underanalyzed in genome-wide association studies (GWAS). Here we demonstrate the benefits of including chrX in GWAS by assessing the contribution of 404,862 chrX SNPs to levels of twelve commonly studied cardiometabolic and anthropometric traits in 19,697 Finnish and Swedish individuals with replication data on 5,032 additional Finns. By using a linear mixed model, we estimate that on average 2.6% of the additive genetic variance in these twelve traits is attributable to chrX, this being in proportion to the number of SNPs in the chromosome. In a chrX-wide association analysis, we identify three novel loci: two for height (rs182838724 near FGF16/ATRX/MAGT1, joint P-value = 2.71×10(-9), and rs1751138 near ITM2A, P-value = 3.03×10(-10)) and one for fasting insulin (rs139163435 in Xq23, P-value = 5.18×10(-9)). Further, we find that effect sizes for variants near ITM2A, a gene implicated in cartilage development, show evidence for a lack of dosage compensation. This observation is further supported by a sex-difference in ITM2A expression in whole blood (P-value = 0.00251), and is also in agreement with a previous report showing ITM2A escapes from X chromosome inactivation (XCI) in the majority of women. Hence, our results show one of the first links between phenotypic variation in a population sample and an XCI-escaping locus and pinpoint ITM2A as a potential contributor to the sexual dimorphism in height. In conclusion, our study provides a clear motivation for including chrX in large-scale genetic studies of complex diseases and traits.
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