| 1. |
- Skoglund, Lena, et al.
(författare)
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Novel Progranulin Mutation Detected in 2 Patients With FTLD
- 2011
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Ingår i: Alzheimer Disease and Associated Disorders. - : Lippincott Williams & Wilkins. - 0893-0341 .- 1546-4156. ; 25:2, s. 173-178
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal lobar degeneration (FTLD) with ubiquitin-positive, tau-negative inclusions, and linkage to chromosome 17 was recently found to be caused by mutations in the progranulin (PGRN) gene. In this study, we screened a group of 51 FTLD patients for PGRN mutations and identified a novel exon 6 splice donor site deletion (IVS6+5_8delGTGA) in 2 unrelated patients. This mutation displayed an altered splicing pattern generating 2 aberrant transcripts and causing frameshifts of the coding sequence, premature termination codons, and a near absence of PGRN mRNA from the mutated alleles most likely through nonsense-mediated decay. The subsequent PGRN haploinsufficiency is consistent with previously described PGRN mutations. We present a molecular characterization of the IVS6+5_8delGTGA mutation and also describe clinical and neuropathologic features from the 2 patients carrying this PGRN mutation. From the screening of these 51 FTLD patients, we could also identify the earlier reported mutation Gln130fs, and several coding sequence variants that are most likely nonpathogenic.
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| 2. |
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| 3. |
- Skoglund, Pontus
(författare)
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Reconstructing the Human Past using Ancient and Modern Genomes
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The study of DNA variation is one of the most promising avenues for learning about the evolutionary and historical past of humans and other species. However, the difficulty associated with obtaining DNA directly from ancient remains have for long kept genomic studies of population history trapped in time; confined to interpreting patterns of modern-day variation without direct historical observations. In this thesis, I outline new approaches for the retrieval, analysis and interpretation of large-scale genomic data from ancient populations, including solutions to overcome problems associated with limited genome coverage, modern-day contamination, temporal differences between samples, and post-mortem DNA damage. I integrate large-scale genomic data sets from ancient remains with modern-day variation to trace the human past; from traits targeted by natural selection in the early ancestors of anatomically modern humans, to their descendants' interbreeding with archaic populations in Eurasia and the spread of agriculture in Europe and Africa. By first reconstructing the earliest population diversification events of early modern humans using a novel large-scale genomic data set from Khoe-San populations in southern Africa, I devise a new approach to search for genomic patterns of selective sweeps in ancestral populations and report evidence for skeletal development as a major target of selection during the emergence of early modern humans. Comparing publicly available genomes from archaic humans, I further find that the distribution of archaic human ancestry in Eurasia is more complex than previously thought. In the first direct genomic study of population structure in prehistoric populations, I demonstrate that individuals associated with farming- and hunter-gatherer complexes in Neolithic Scandinavia were strongly genetically differentiated, and direct comparisons with modern-day populations as well as other prehistoric individuals from Southern Europe suggest that this structure originated from Northward expansion of Neolithic farming populations. Finally, I develop a bioinformatic approach for removing modern-day contamination from large-scale ancient DNA sequencing data, and use this method to reconstruct the complete mitochondrial genome sequence of a Siberian Neandertal that is affected by substantial modern-day contamination.
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| 4. |
- Wang, Chao, et al.
(författare)
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Approaching the Optimal Diversity-Multiplexing Tradeoff in a Four-node Cooperative Network
- 2010
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Ingår i: IEEE Transactions on Wireless Communications. - : IEEE Communications Society. - 1536-1276 .- 1558-2248. ; 9:12, s. 3690-3700
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Tidskriftsartikel (refereegranskat)abstract
- A novel cooperative diversity transmission protocol is proposed for a four-node network, in which a single-antenna source communicates with an N-antenna destination with the help of two K-antenna half-duplex decode-and-forward (DF) relays. The proposed shifted successive DF relaying (SSDFR) protocol asymptotically achieves the optimal diversity-multiplexing tradeoff (DMT) the system can provide. The resulting DMT performance does not require complex coding strategies at the relays, extremely strong or weak inter-relay channel conditions, or feedback from the destination to the source, which highlights the advantages of the proposed protocol over state of the art techniques.
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