| 1. |
- Berglund, Eva C, et al.
(författare)
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Accurate detection of subclonal single nucleotide variants in whole genome amplified and pooled cancer samples using HaloPlex target enrichment
- 2013
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Ingår i: BMC Genomics. - : BioMed Central. - 1471-2164. ; 14, s. 856-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Target enrichment and resequencing is a widely used approach for identification of cancer genes and genetic variants associated with diseases. Although cost effective compared to whole genome sequencing, analysis of many samples constitutes a significant cost, which could be reduced by pooling samples before capture. Another limitation to the number of cancer samples that can be analyzed is often the amount of available tumor DNA. We evaluated the performance of whole genome amplified DNA and the power to detect subclonal somatic single nucleotide variants in non-indexed pools of cancer samples using the HaloPlex technology for target enrichment and next generation sequencing. Results: We captured a set of 1528 putative somatic single nucleotide variants and germline SNPs, which were identified by whole genome sequencing, with the HaloPlex technology and sequenced to a depth of 792-1752. We found that the allele fractions of the analyzed variants are well preserved during whole genome amplification and that capture specificity or variant calling is not affected. We detected a large majority of the known single nucleotide variants present uniquely in one sample with allele fractions as low as 0.1 in non-indexed pools of up to ten samples. We also identified and experimentally validated six novel variants in the samples included in the pools. Conclusion: Our work demonstrates that whole genome amplified DNA can be used for target enrichment equally well as genomic DNA and that accurate variant detection is possible in non-indexed pools of cancer samples. These findings show that analysis of a large number of samples is feasible at low cost, even when only small amounts of DNA is available, and thereby significantly increases the chances of indentifying recurrent mutations in cancer samples.
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| 2. |
- Besnier, Francois, et al.
(författare)
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Fine mapping and replication of QTL in outbred chicken advanced intercross lines
- 2011
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Ingår i: Genetics Selection Evolution. - Paris : Springer Science and Business Media LLC. - 0999-193X .- 1297-9686. ; 43, s. 3-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Linkage mapping is used to identify genomic regions affecting the expression of complex traits. However, when experimental crosses such as F2 populations or backcrosses are used to map regions containing a Quantitative Trait Locus (QTL), the size of the regions identified remains quite large, i.e. 10 or more Mb. Thus, other experimental strategies are needed to refine the QTL locations. Advanced Intercross Lines (AIL) are produced by repeated intercrossing of F2 animals and successive generations, which decrease linkage disequilibrium in a controlled manner. Although this approach is seen as promising, both to replicate QTL analyses and fine-map QTL, only a few AIL datasets, all originating from inbred founders, have been reported in the literature.METHODS: We have produced a nine-generation AIL pedigree (n = 1529) from two outbred chicken lines divergently selected for body weight at eight weeks of age. All animals were weighed at eight weeks of age and genotyped for SNP located in nine genomic regions where significant or suggestive QTL had previously been detected in the F2 population. In parallel, we have developed a novel strategy to analyse the data that uses both genotype and pedigree information of all AIL individuals to replicate the detection of and fine-map QTL affecting juvenile body weight.RESULTS: Five of the nine QTL detected with the original F2 population were confirmed and fine-mapped with the AIL, while for the remaining four, only suggestive evidence of their existence was obtained. All original QTL were confirmed as a single locus, except for one, which split into two linked QTL.CONCLUSIONS: Our results indicate that many of the QTL, which are genome-wide significant or suggestive in the analyses of large intercross populations, are true effects that can be replicated and fine-mapped using AIL. Key factors for success are the use of large populations and powerful statistical tools. Moreover, we believe that the statistical methods we have developed to efficiently study outbred AIL populations will increase the number of organisms for which in-depth complex traits can be analyzed.
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| 3. |
- Burman, Pia, et al.
(författare)
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Deaths Among Adult Patients With Hypopituitarism: Hypocortisolism During Acute Stress, and De Novo Malignant Brain Tumors Contribute to an Increased Mortality
- 2013
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 98:4, s. 1466-1475
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Tidskriftsartikel (refereegranskat)abstract
- Context: Patients with hypopituitarism have an increased standardized mortality rate. The basis for Objective: To investigate in detail the cause of death in a large cohort of patients with hypopituitarism Design and Methods: All-cause and cause-specific mortality in 1286 Swedish patients with Main Outcome Measures: Standardized mortality ratios (SMR) were calculated, with stratification for Results: An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence Conclusion: Two important causes of excess mortality were identified: first, adrenal crisis in response
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| 6. |
- Dahlqvist, Per, et al.
(författare)
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Nationellt kort vid binjurbarksvikt : nytt varningskort kan leda till bättre handläggning och ökad patientsäkerhet
- 2011
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 108:44, s. 2226-2227
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Tidskriftsartikel (refereegranskat)abstract
- Akut binjurebarkssvikt (akut kortisolbrist/Addisonkris) är en ovanlig men viktig differentialdiagnos vid akut cirkulationssvikt. De flesta fall av Addisonkris drabbar patienter med känd binjurebarkssvikt, oftast i samband med gastroenterit eller annan infektion. Noggrann och tydlig information och utbildning av patienter, anhöriga och sjukvårdspersonal behövs för att undvika sjuklighet och dödsfall i akut binjurebarkssvikt. Ett nationellt varningskort i kreditkortsformat har tagits fram till patienter med binjurebarkssvikt för att uppmärksamma och förbättra handläggningen av detta potentiellt livshotande tillstånd
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| 7. |
- Dahlqvist, Per, et al.
(författare)
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Nationellt kort vid binjurebarkssvikt : Nytt varningskort kan leda till bättre handläggning och ökad patientsäkerhet
- 2012
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 108:44, s. 2226-2227
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Tidskriftsartikel (refereegranskat)abstract
- Akut binjurebarkssvikt (akut kortisolbrist/Addisonkris) är en ovanlig men viktig differentialdiagnos vid akut cirkulationssvikt.De flesta fall av Addisonkris drabbar patienter med känd binjurebarkssvikt, oftast i samband med gastroenterit eller annan infektion.Noggrann och tydlig information och utbildning av patienter, anhöriga och sjukvårdspersonal behövs för att undvika sjuklighet och dödsfall i akut binjurebarkssvikt.Ett nationellt varningskort i kreditkortsformat har tagits fram till patienter med binjurebarkssvikt för att uppmärksamma och förbättra handläggningen av detta potentiellt livshotande tillstånd.
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| 8. |
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| 9. |
- Ebadat, Afrooz, et al.
(författare)
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Applications Oriented Input Design in Time-Domain Through Cyclic Methods
- 2014
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Konferensbidrag (refereegranskat)abstract
- In this paper we propose a method for applications oriented input design for linear systems in open-loop under time-domain constraints on the amplitude of input and output signals. The method guarantees a desired control performance for the estimated model in minimum time, by imposing some lower bound on the information matrix. The problem is formulated as a time-domain optimization problem, which is non-convex. This is addressed through an alternating method, where we separate the problem into two steps and at each step we optimize the cost function with respect to one of two variables. We alternate between these two steps until convergence. A time recursive input design algorithm is performed, which enables us to use the algorithm with control. Therefore, a receding horizon framework is used to solve each optimization problem. Finally, we illustrate the method with a numerical example which shows the good ability of the proposed approach in generating an optimal input signal.
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| 10. |
- Ek, Weronica, et al.
(författare)
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Genetic analysis of metabolic traits in an intercross between body weight-selected chicken lines
- 2010
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Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 42:1, s. 20-22
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Tidskriftsartikel (refereegranskat)abstract
- A network of four interacting loci has been reported previously to influence growth in two lines of chickens divergently selected for body weight at 56 days of age. Located on chromosomes 3 (Growth4), 4 (Growth6), 7 (Growth9), and 20 (Growth12), they explained nearly half of the difference in body weight at selection age between the two lines. The original study reported effects on body weight and fat deposition, but no attempts were made to explore the effects of the network on other phenotypes measured in the F(2) population. In this study we conducted further analyses to evaluate the specific effects of the four-locus network on other metabolic traits as well as refining results from the original study by including a larger number of genetic markers in the quantitative trait locus (QTL) regions. We confirm the previously described effect of the epistatic network on body weight and show that the network increases the total amount of muscle and fat as well as the weight of the internal organs. The network as a whole did not change the relative content of any studied organs or tissues in the body. There was, however, a significant interaction between the loci on chromosomes 3 and 7 that changed the relative proportion of abdominal fat and breast muscle in the chicken by increasing abdominal fat weight without a corresponding increase in muscle mass.
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