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- Gunnarsson, Rebeqa, et al.
(author)
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Screening for copy-number alterations and loss of heterozygosity in chronic lymphocytic leukemia-A comparative study of four differently designed, high resolution microarray platforms
- 2008
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In: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 93, s. 0536-0536
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Journal article (peer-reviewed)abstract
- Screening for gene copy-number alterations (CNAs) has improved by applying genome-wide microarrays, where SNP arrays also allow analysis of loss of heterozygozity (LOH). We here analyzed 10 chronic lymphocytic leukemia (CLL) samples using four different high-resolution platforms: BAC arrays (32K), oligonucleotide arrays (185K, Agilent), and two SNP arrays (250K, Affymetrix and 317K, Illumina). Cross-platform comparison revealed 29 concordantly detected CNAs, including known recurrent alterations, which confirmed that all platforms are powerful tools when screening for large aberrations. However, detection of 32 additional regions present in 2-3 platforms illustrated a discrepancy in detection of small CNAs, which often involved reported copy-number variations. LOH analysis using dChip revealed concordance of mainly large regions, but showed numerous, small nonoverlapping regions and LOH escaping detection. Evaluation of baseline variation and copy-number ratio response showed the best performance for the Agilent platform and confirmed the robustness of BAC arrays. Accordingly, these platforms demonstrated a higher degree of platform-specific CNAs. The SNP arrays displayed higher technical variation, although this was compensated by high density of elements. Affymetrix detected a higher degree of CNAs compared to Illumina, while the latter showed a lower noise level and higher detection rate in the LOH analysis. Large-scale studies of genomic aberrations are now feasible, but new tools for LOH analysis are requested.
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| 2. |
- Sawcer, Stephen, et al.
(author)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Journal article (peer-reviewed)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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| 4. |
- Liljedahl, Lillemor Claesson, et al.
(author)
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Rapid and sensitive response of Greenland’s groundwater system to ice sheet change
- 2021
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In: Nature Geoscience. - : Springer Nature. - 1752-0894 .- 1752-0908. ; 14:10, s. 751-755
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Journal article (peer-reviewed)abstract
- Greenland Ice Sheet mass loss is impacting connected terrestrial and marine hydrologic systems with global consequences. Groundwater is a key component of water cycling in the Arctic, underlying the 1.7e6 km2 ice sheet and forming offshore freshwater reserves. However, despite its vast extent, the response of Greenland’s groundwater to ongoing ice sheet change is unknown. Here we present in-situ observations of deep groundwater conditions under the Greenland Ice Sheet, obtained in a 651-metre-long proglacial bedrock borehole angled under the ice sheet margin. We find that Greenland’s groundwater system responds rapidly and sensitively to relatively minor ice sheet forcing. Hydraulic head clearly varies over multi-annual, seasonal and diurnal timescales, which we interpret as a response to fluid pressure forcing at the ice/bed interface associated with changes in overlying ice loading and ice sheet hydrology. We find a systematic decline in hydraulic head over the eight-year observational period is linked primarily to ice sheet mass loss. Ongoing and future ice thinning will probably reduce groundwater discharge rates, with potential impacts to submarine freshwater discharge, freshwater delivery to fjords and biogeochemical fluxes in the Arctic.
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| 7. |
- Ruskeeniemi, Timo, et al.
(author)
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Subglacial permafrost evidencing re-advance of the Greenland Ice Sheet over frozen ground
- 2018
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In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 199, s. 174-187
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Journal article (peer-reviewed)abstract
- Greenland Ice Sheet (GrIS) covers an area of 1.7 million km(2). It has been an important source of climate information and the air temperature history of Greenland is well known. However, the thermal history and temperature conditions of the Greenland bedrock are poorly known. There are only few records on the temperature of the proglacial bedrock and no records on bedrock temperature underneath the ice sheet. The Greenland Analogue Project (GAP) recently investigated hydrological, hydrogeological and geochemical processes in Kangerlussuaq, West Greenland. Because permafrost has a major hydrological impact in Arctic regions, the cryogenic structure of the bedrock was an important research topic. From previous studies it was already known that Kangerlussuaq is located within the zone of continuous permafrost. Temperature profiling in a new research borehole, extending horizontally 30 m underneath the ice sheet, revealed that permafrost is 350 m deep at the ice margin. This result raised the question how far the permafrost extends under the ice sheet? In order to investigate the thermal properties, we made a series of electromagnetic (EM) soundings at the ice margin area - on proglacial area and on the ice sheet - and detected, that subglacial permafrost extends at least 2 km from the ice margin to inland. We also observed a patchy unfrozen sediment layer between the ice and the frozen bedrock. Possible existence of subglacial sediments and their role in ice dynamics has been debated in many recent papers. Our successful campaign shows that geophysics can be used for bedrock investigations through thick ice, which is known to be challenging for electromagnetic methods. Our results provide the first direct evidence supporting the proposed Holocene ice re-advance over frozen ground, and contribute to the discussion on the rapid climate changes in past, to the future of the ice sheet under warming climate and hydrogeology at the ice margin.
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