| 1. |
- Johansson, Anna Maria, et al.
(author)
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Variation in the VWF Gene in Swedish Patients with Type 1 von Willebrand Disease.
- 2011
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In: Annals of Human Genetics. - : Wiley. - 1469-1809 .- 0003-4800. ; 75, s. 447-455
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Journal article (peer-reviewed)abstract
- The spectrum of mutations in the von Willebrand factor (VWF) gene in a Swedish type 1 von Willebrand disease (VWD) population was investigated. To gain more knowledge about the dynamics of VWD mutations, the data were analyzed from a population genetics perspective. The VWF gene was resequenced in 54 Swedish patients diagnosed with type 1 VWD. Fifty-five variable sites were located in exons, 10 in the promoter and 38 in introns. The spectrum of mutations was similar to a European study, but included 10 new candidate mutations. The synonymous sites were evenly distributed along the coding sequence, whereas nonsynonymous sites were located into three clusters. Overall, 44% of patients had no mutations or candidate mutations and no promoter haplotype was significantly associated with disease. In 11 patients (20%), more than one mutation or candidate mutation was detected. The allelic identity for the putative disease-causing mutations was approximately 0.1, compatible with an overall disease frequency of 1%. VWF sequences for exon 28 from eight monkey species were compared with the variable positions found in our patients. Positions classified as mutations were overrepresented among sites that were fixed in all eight monkey species. No general increase of the mutation rate was found for the pseudogene region.
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| 2. |
- Jakobsson, Mattias, et al.
(author)
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A unique recent origin of the allotetraploid species Arabidopsis suecica: Evidence from nuclear DNA markers
- 2006
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In: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 23:6, s. 1217-1231
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Journal article (peer-reviewed)abstract
- A coalescent-based method was used to investigate the origins of the allotetraploid Arabidopsis suecica, using 52 nuclear microsatellite loci typed in eight individuals of A. suecica and 14 individuals of its maternal parent Arabidopsis thaliana, and four short fragments of genomic DNA sequenced in a sample of four individuals of A. suecica and in both its parental species A. thaliana and Arabidopsis arenosa. All loci were variable in A. thaliana but only 24 of the 52 microsatellite loci and none of the four sequence fragments were variable in A. suecica. We explore a number of possible evolutionary scenarios for A. suecica and conclude that it is likely that A. suecica has a recent, unique origin between 12,000 and 300,000 years ago. The time estimates depend strongly on what is assumed about population growth and rates of mutation. When combined with what is known about the history of glaciations, our results suggest that A. suecica originated south of its present distribution in Sweden and Finland and then migrated north, perhaps in the wake of the retreating ice.
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| 3. |
- Jakobsson, Mattias, et al.
(author)
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Evolution of chloroplast mononucleotide microsatellites in Arabidopsis thaliana
- 2007
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In: Theoretical And Applied Genetics. - : Springer Science and Business Media LLC. - 0040-5752 .- 1432-2242. ; 114:2, s. 223-235
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Journal article (peer-reviewed)abstract
- The level of variation and the mutation rate were investigated in an empirical study of 244 chloroplast microsatellites in 15 accessions of Arabidopsis thaliana. In contrast to SNP variation, microsatellite variation in the chloroplast was found to be common, although less common than microsatellite variation in the nucleus. No microsatellite variation was found in coding regions of the chloroplast. To evaluate different models of microsatellite evolution as possible explanations for the observed pattern of variation, the length distribution of microsatellites in the published DNA sequence of the A. thaliana chloroplast was subsequently used. By combining information from these two analyses we found that the mode of evolution of the chloroplast mononucleotide microsatellites was best described by a linear relation between repeat length and mutation rate, when the repeat lengths exceeded about 7 bp. This model can readily predict the variation observed in non-coding chloroplast DNA. It was found that the number of uninterrupted repeat units had a large impact on the level of chloroplast microsatellite variation. No other factors investigated-such as the position of a locus within the chromosome, or imperfect repeats-appeared to affect the variability of chloroplast microsatellites. By fitting the slippage models to the Genbank sequence of chromosome 1, we show that the difference between microsatellite variation in the nucleus and the chloroplast is largely due to differences in slippage rate.
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| 4. |
- Jakobsson, Mattias, et al.
(author)
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The evolutionary history of the common chloroplast genome of Arabidopsis thaliana and A. suecica.
- 2007
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In: Journal of evolutionary biology. - : Wiley. - 1420-9101 .- 1010-061X. ; 20:1, s. 104-121
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Journal article (peer-reviewed)abstract
- The evolutionary history of the common chloroplast (cp) genome of the allotetraploid Arabidopsis suecica and its maternal parent A. thaliana was investigated by sequencing 50 fragments of cpDNA, resulting in 98 polymorphic sites. The variation in the A. suecica sample was small, in contrast to that of the A. thaliana sample. The time to the most recent common ancestor (T-MRCA) of the A. suecica cp genome alone was estimated to be about one 37th of the T-MRCA of both the A. thaliana and A. suecica cp genomes. This corresponds to A. suecica having a MRCA between 10 000 and 50 000 years ago, suggesting that the entire species originated during, or before, this period of time, although the estimates are sensitive to assumptions made about population size and mutation rate. The data was also consistent with the hypothesis of A. suecica being of single origin. Isolation-by-distance and population structure in A. thaliana depended upon the geographical scale analysed; isolation-by-distance was found to be weak on the global scale but locally pronounced. Within the genealogical cp tree of A. thaliana, there were indications that the root of the A. suecica species is located among accessions of A. thaliana that come primarily from central Europe. Selective neutrality of the cp genome could not be rejected, despite the fact that it contains several completely linked protein-coding genes.
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| 5. |
- Lindahl, Pernilla, et al.
(author)
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Copy number variants in the kallikrein gene cluster.
- 2013
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7
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Journal article (peer-reviewed)abstract
- The kallikrein gene family (KLK1-KLK15) is the largest contiguous group of protease genes within the human genome and is associated with both risk and outcome of cancer and other diseases. We searched for copy number variants in all KLK genes using quantitative PCR analysis and analysis of inheritance patterns of single nucleotide polymorphisms. Two deletions were identified: one 2235-bp deletion in KLK9 present in 1.2% of alleles, and one 3394-bp deletion in KLK15 present in 4.0% of alleles. Each deletion eliminated one complete exon and created out-of-frame coding that eliminated the catalytic triad of the resulting truncated gene product, which therefore likely is a non-functional protein. Deletion breakpoints identified by DNA sequencing located the KLK9 deletion breakpoint to a long interspersed element (LINE) repeated sequence, while the deletion in KLK15 is located in a single copy sequence. To search for an association between each deletion and risk of prostate cancer (PC), we analyzed a cohort of 667 biopsied men (266 PC cases and 401 men with no evidence of PC at biopsy) using short deletion-specific PCR assays. There was no association between evidence of PC in this cohort and the presence of either gene deletion. Haplotyping revealed a single origin of each deletion, with most recent common ancestor estimates of 3000-8000 and 6000-14 000 years for the deletions in KLK9 and KLK15, respectively. The presence of the deletions on the same haplotypes in 1000 Genomes data of both European and African populations indicate an early origin of both deletions. The old age in combination with homozygous presence of loss-of-function variants suggests that some kallikrein-related peptidases have non-essential functions.
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| 6. |
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