| 1. |
- Dorum, Guro, et al.
(författare)
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Mixtures with relatives and linked markers
- 2016
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Ingår i: International journal of legal medicine. - : SPRINGER. - 0937-9827 .- 1437-1596. ; 130:3, s. 621-634
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Tidskriftsartikel (refereegranskat)abstract
- Mixture DNA profiles commonly appear in forensic genetics, and a large number of statistical methods and software are available for such cases. However, most of the literature concerns mixtures where the contributors are assumed unrelated and the genetic markers are unlinked. In this paper, we consider mixtures of linked markers and related contributors. If no relationships are involved, linkage can be ignored. While unlinked markers can be treated independently, linkage introduces dependencies. The use of linked markers presents statistical and computational challenges, but may also lead to a considerable increase in power since the number of markers available is much larger if we do not require the markers to be unlinked. In addition, some cases that cannot be solved with an unlimited number of unlinked autosomal markers can be solved with linked markers. We focus on two special cases of linked markers: pairs of linked autosomal markers and X-chromosomal markers. A framework is presented for calculation of likelihood ratios for mixtures with general relationships and with linkage between any number of markers. Finally, we explore the effect of linkage disequilibrium, also called allelic association, on the likelihood ratio.
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| 2. |
- Grandell, Ida, et al.
(författare)
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A SNP panel for identity and kinship testing using massive parallel sequencing
- 2016
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Ingår i: International journal of legal medicine. - : SPRINGER. - 0937-9827 .- 1437-1596. ; 130:4, s. 905-914
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Tidskriftsartikel (refereegranskat)abstract
- Within forensic genetics, there is still a need for supplementary DNA marker typing in order to increase the power to solve cases for both identity testing and complex kinship issues. One major disadvantage with current capillary electrophoresis (CE) methods is the limitation in DNA marker multiplex capability. By utilizing massive parallel sequencing (MPS) technology, this capability can, however, be increased. We have designed a customized GeneRead DNASeq SNP panel (Qiagen) of 140 previously published autosomal forensically relevant identity SNPs for analysis using MPS. One single amplification step was followed by library preparation using the GeneRead Library Prep workflow (Qiagen). The sequencing was performed on a MiSeq System (Illumina), and the bioinformatic analyses were done using the software Biomedical Genomics Workbench (CLC Bio, Qiagen). Forty-nine individuals from a Swedish population were genotyped in order to establish genotype frequencies and to evaluate the performance of the assay. The analyses showed to have a balanced coverage among the included loci, and the heterozygous balance showed to have less than 0.5 % outliers. Analyses of dilution series of the 2800M Control DNA gave reproducible results down to 0.2 ng DNA input. In addition, typing of FTA samples and bone samples was performed with promising results. Further studies and optimizations are, however, required for a more detailed evaluation of the performance of degraded and PCR-inhibited forensic samples. In summary, the assay offers a straightforward sample-to-genotype workflow and could be useful to gain information in forensic casework, for both identity testing and in order to solve complex kinship issues.
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| 3. |
- Green, Henrik, et al.
(författare)
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The use of FTA cards to acquire DNA profiles from postmortem cases
- 2019
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Ingår i: International journal of legal medicine. - : SPRINGER. - 0937-9827 .- 1437-1596. ; 133:6, s. 1651-1657
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Tidskriftsartikel (refereegranskat)abstract
- Filter papers have been used for many years in different applications of molecular biology and have been proven to be a stable way to store DNA waiting to be analyzed. Sampling of DNA on FTA (Flinders Technology Associates) cards is convenient and cost effective compared to alternative approaches involving DNA extractions and storage of DNA extracts. FTA cards are analyzed at many forensic laboratories, and the way to perform direct genetic profiling on buccal swab cards has developed into an almost industrial process. The possibility to include postmortem (PM) samples into an FTA-based workflow would facilitate and speed up the genetic identification process compared to conventional methods, both on a regular basis and in a mass casualty event. In this study, we investigated if FTA cards may be used to carry tissue DNA from deceased and present a high-quality DNA profile from the individual in order to be useful for the identification process. The study also aimed to investigate if a specific body tissue would be preferable, and if decomposed tissue is suitable at all to put on an FTA card in order to obtain a DNA profile. We have compared the quality of the DNA profiles acquired from postmortem tissue on FTA cards, with the results acquired with conventional methods from reference bone/muscle samples from the same individual. Several types of tissues have been tested from different identification cases and scenarios. We concluded that tissue cells from inner organs are suitable to put on FTA cards, and that the obtained DNA profiles have the potential to serve as PM data for identification purposes. In cases including compromised samples, however, it is recommended to keep the tissue sample as a backup if further DNA has to be extracted.
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| 4. |
- Hedell, Ronny, 1985, et al.
(författare)
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Determining the optimal forensic DNA analysis procedure following investigation of sample quality
- 2018
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Ingår i: International Journal of Legal Medicine. - : Springer Science and Business Media LLC. - 0937-9827 .- 1437-1596. ; 132:4, s. 955-966
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 Springer-Verlag GmbH Germany Crime scene traces of various types are routinely sent to forensic laboratories for analysis, generally with the aim of addressing questions about the source of the trace. The laboratory may choose to analyse the samples in different ways depending on the type and quality of the sample, the importance of the case and the cost and performance of the available analysis methods. Theoretically well-founded guidelines for the choice of analysis method are, however, lacking in most situations. In this paper, it is shown how such guidelines can be created using Bayesian decision theory. The theory is applied to forensic DNA analysis, showing how the information from the initial qPCR analysis can be utilized. It is assumed the alternatives for analysis are using a standard short tandem repeat (STR) DNA analysis assay, using the standard assay and a complementary assay, or the analysis may be cancelled following quantification. The decision is based on information about the DNA amount and level of DNA degradation of the forensic sample, as well as case circumstances and the cost for analysis. Semi-continuous electropherogram models are used for simulation of DNA profiles and for computation of likelihood ratios. It is shown how tables and graphs, prepared beforehand, can be used to quickly find the optimal decision in forensic casework.
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| 5. |
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| 6. |
- Kling, D., et al.
(författare)
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A general model for likelihood computations of genetic marker data accounting for linkage, linkage disequilibrium, and mutations
- 2015
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Ingår i: International Journal of Legal Medicine. - : Springer Science and Business Media LLC. - 0937-9827 .- 1437-1596. ; 129:5, s. 943-954
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Tidskriftsartikel (refereegranskat)abstract
- Several applications necessitate an unbiased determination of relatedness, be it in linkage or association studies or in a forensic setting. An appropriate model to compute the joint probability of some genetic data for a set of persons given some hypothesis about the pedigree structure is then required. The increasing number of markers available through high-density SNP microarray typing and NGS technologies intensifies the demand, where using a large number of markers may lead to biased results due to strong dependencies between closely located loci, both within pedigrees (linkage) and in the population (allelic association or linkage disequilibrium (LD)). We present a new general model, based on a Markov chain for inheritance patterns and another Markov chain for founder allele patterns, the latter allowing us to account for LD. We also demonstrate a specific implementation for X chromosomal markers that allows for computation of likelihoods based on hypotheses of alleged relationships and genetic marker data. The algorithm can simultaneously account for linkage, LD, and mutations. We demonstrate its feasibility using simulated examples. The algorithm is implemented in the software FamLinkX, providing a user-friendly GUI for Windows systems (FamLinkX, as well as further usage instructions, is freely available at www.famlink.se). Our software provides the necessary means to solve cases where no previous implementation exists. In addition, the software has the possibility to perform simulations in order to further study the impact of linkage and LD on computed likelihoods for an arbitrary set of markers.
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| 7. |
- Malmqvist, Erik, et al.
(författare)
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Ethical aspects of medical age assessment in the asylum process : a Swedish perspective
- 2018
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Ingår i: International journal of legal medicine. - : Springer Science and Business Media LLC. - 0937-9827 .- 1437-1596. ; 132:3, s. 815-823
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Tidskriftsartikel (refereegranskat)abstract
- According to European regulations and the legisla-tions of individual member states, children who seek asylum have a different set of rights than adults in a similar position.To protect these rights and ensure rule of law, migration authorities are commonly required to assess the age of asylum seekers who lack reliable documentation, including throug hvarious medical methods. However, many healthcare professionals and other commentators consider medical age assessment to be ethically problematic. This paper presents a simplified and amended account of the main findings of a recent ethical analysis of medical age assessment in the asylum process commissioned by the Swedish National Board of Healthand Welfare. A number of ethical challenges related to conflicting goals, equality and fairness, autonomy and informed consent, privacy and integrity, and professional values and roles are identified and analysed. It is concluded that most of these challenges can be met, but that this requires a system where the assessment is sufficiently accurate and where adequate safeguards are in place. Two important ethical questions are found to warrant further analysis. The first is whether asylum seekers’consent to the procedure can be considered genuinely voluntary. The second is whether and how medica lage assessments could affect negative public attitudes towards asylum seekers or discriminatory societal views more generally.
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| 8. |
- Mostad, Petter, 1964, et al.
(författare)
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Error rates for unvalidated medical age assessment procedures
- 2019
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Ingår i: International Journal of Legal Medicine. - : Springer Science and Business Media LLC. - 0937-9827 .- 1437-1596. ; 133:2, s. 613-623
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Tidskriftsartikel (refereegranskat)abstract
- During 2014-2015, Sweden received asylum applications from more than 240,000 people, of which more than 40,000 were termed unaccompanied minors. In a large number of cases, claims by asylum seekers of being below 18 years were not trusted by Swedish authorities. To handle the situation, the Swedish national board of forensic medicine (Rattsmedicinalverket, RMV) was assigned by the government to create a centralized system for medical age assessments. RMV introduced a procedure including two biological age indicators; x-ray of the third molars and magnetic resonance imaging of the distal femoral epiphysis. In 2017, a total of 9617 males and 337 females were subjected to this procedure. No validation study for the procedure was however published, and the observed number of cases with different maturity combinations in teeth and femur were unexpected given the claims originally made by RMV. We present a general stochastic model enabling us to study which combinations of age indicator model parameters and age population profiles are consistent with the observed 2017 data for males. We find that, contrary to some RMV claims, maturity of the femur, as observed by RMV, appears on average well before maturity of teeth. According to our estimates, approximately 15% of the tested males were children. These children had an approximate 33% risk of being classified as adults. The corresponding risk for an adult to be misclassified as a child was approximately 7%. We determine uncertainties and ranges of estimates under reasonable perturbations of the prior.
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| 9. |
- Nilsson, Gunnel, et al.
(författare)
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Validation of an LC-MS/MS method for the determination of zopiclone, N-desmethylzopiclone and 2-amino-5-chloropyridine in whole blood and its application to estimate the original zopiclone concentration in stored specimens
- 2015
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Ingår i: International journal of legal medicine. - : Springer. - 0937-9827 .- 1437-1596. ; 129:2, s. 269-277
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Tidskriftsartikel (refereegranskat)abstract
- 2-amino-5-chloropyridine (ACP) is a degradation product of zopiclone (ZOP) and may be formed when blood specimens are stored. ZOP instability in blood makes interpretation of concentrations difficult especially in cases of prolonged sample storage. This study investigated how ACP could be used to estimate the original concentration of ZOP in authentic samples. For that purpose, an analytical LC-MS/MS method for the quantitation of ACP, ZOP and the metabolite Ndesmethylzopiclone (NDZOP) in blood was validated. The method was then applied to investigate ACP formation, ZOP and NDZOP degradation in stored ZOP post-dosed authentic whole blood and two mathematical models were used to calculate the original concentration of ZOP. During storage, ACP was formed in amounts equimolar to the ZOP and NDZOP degradation. Results from samples in which ACP had been formed were used to test two models to estimate the original ZOP concentration. The correlation tests of the models showed strong correlations to the original ZOP concentration (r=0.960 and r=0.955) with p<0.01. This study showed that the equimolar degradation of ZOP and NDZOP to ACP could be used to estimate the original concentration of the unstable ZOP.
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| 10. |
- Persson, Anders, et al.
(författare)
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Temperature-corrected postmortem 3-T MR quantification of histopathological early acute and chronic myocardial infarction: a feasibility study
- 2018
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Ingår i: International journal of legal medicine. - : SPRINGER. - 0937-9827 .- 1437-1596. ; 132:2, s. 541-549
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Tidskriftsartikel (refereegranskat)abstract
- The goal of the present study was to evaluate if quantitative postmortem cardiac 3-T magnetic resonance (QPMCMR) T1 and T2 relaxation times and proton density values of histopathological early acute and chronic myocardial infarction differ to the quantitative values of non-pathologic myocardium and other histopathological age stages of myocardial infarction with regard to varying corpse temperatures. In 60 forensic corpses (25 female, 35 male), a cardiac 3-T MR quantification sequence was performed prior to autopsy and cardiac dissection. Core body temperature was assessed during MR examinations. Focal myocardial signal alterations in synthetically generated MR images were measured for their T1, T2, and proton density (PD) values. Locations of signal alteration measurements in PMCMR were targeted at heart dissection, and myocardial tissue specimens were taken for histologic examinations. Quantified signal alterations in QPMCMR were correlated to their according histologic age stage of myocardial infarction, and quantitative values were corrected for a temperature of 37 A degrees C. In QPMCMR, 49 myocardial signal alterations were detected in 43 of 60 investigated hearts. Signal alterations were diagnosed histologically as early acute (n = 16), acute (n = 10), acute with hemorrhagic component (n = 9), subacute (n = 3), and chronic (n = 11) myocardial infarction. Statistical analysis revealed that based on their temperature-corrected quantitative T1, T2, and PD values, a significant difference between early acute, acute, and chronic myocardial infarction can be determined. It can be concluded that quantitative 3-T postmortem cardiac MR based on temperature-corrected T1, T2, and PD values may be feasible for pre-autopsy diagnosis of histopathological early acute, acute, and chronic myocardial infarction, which needs to be confirmed histologically.
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| 11. |
- Schwendener, Nicole, et al.
(författare)
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Temperature-corrected post-mortem 1.5 T MRI quantification of non-pathologic upper abdominal organs
- 2017
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Ingår i: International journal of legal medicine. - : SPRINGER. - 0937-9827 .- 1437-1596. ; 131:5, s. 1369-1376
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Tidskriftsartikel (refereegranskat)abstract
- The present study aimed to evaluate if simultaneous temperature-corrected T1, T2, and proton density (PD) 1.5 T post-mortem MR quantification [quantitative post-mortem magnetic resonance imaging (QPMMRI)] is feasible for characterizing and discerning non-pathologic upper abdominal organs (liver, spleen, pancreas, kidney) with regard to varying body temperatures. QPMMRI was performed on 80 corpses (25 females, 55 males; mean age 56.2 years, SD 17.2) prior to autopsy. Core body temperature was measured during QPMMRI. Quantitative T1, T2, and PD values were measured in the liver, pancreas, spleen, and left kidney and temperature corrected to 37 A degrees C. Histologic examinations were conducted on each measured organ to determine non-pathologic organs. Quantitative T1, T2, and PD values of non-pathologic organs were ANOVA tested against values of other non-pathologic organ types. Based on temperature-corrected quantitative T1, T2, and PD values, ANOVA testing verified significant differences between the non-pathologic liver, spleen, pancreas, and left kidneys. Temperature-corrected 1.5 T QPMMRI based on T1, T2, and PD values may be feasible for characterization and differentiation of the non-pathologic liver, spleen, pancreas, and kidney. The results may provide a base for future specific pathology diagnosis of upper abdominal organs in post-mortem imaging.
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| 12. |
- Stattin, Eva-Lena, et al.
(författare)
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Genetic screening in sudden cardiac death in the young can save future lives
- 2016
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Ingår i: International Journal of Legal Medicine. - : Springer Science and Business Media LLC. - 0937-9827 .- 1437-1596. ; 130:1, s. 59-66
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Tidskriftsartikel (refereegranskat)abstract
- Autopsy of sudden cardiac death (SCD) in the young shows a structurally and histologically normal heart in about one third of cases. Sudden death in these cases is believed to be attributed in a high percentage to inherited arrhythmogenic diseases. The purpose of this study was to investigate the value of performing post-mortem genetic analysis for autopsy-negative sudden unexplained death (SUD) in 1 to 35 year olds. From January 2009 to December 2011, samples from 15 cases suffering SUD were referred to the Department of Clinical Genetics, UmeAyen University Hospital, Sweden, for molecular genetic evaluation. PCR and bidirectional Sanger sequencing of genes important for long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome type 1 (BrS1), and catecholaminergic polymorphic ventricular tachycardia (CPVT) (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, and RYR2) was performed. Multiplex ligation-dependent probe amplification (MLPA) was used to detect large deletions or duplications in the LQTS genes. Six pathogenic sequence variants (four LQTS and two CPVT) were discovered in 15 SUD cases (40 %). Ten first-degree family members were found to be mutation carriers (seven LQTS and three CPVT). Cardiac ion channel genetic testing in autopsy-negative sudden death victims has a high diagnostic yield, with identification of the disease in 40 % of families. First-degree family members should be offered predictive testing, clinical evaluation, and treatment with the ultimate goal to prevent sudden death.
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| 13. |
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| 14. |
- Zech, Wolf-Dieter, et al.
(författare)
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Post-mortem 1.5T MR quantification of regular anatomical brain structures
- 2016
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Ingår i: International journal of legal medicine. - : Springer. - 0937-9827 .- 1437-1596. ; 130:4, s. 1071-1080
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Tidskriftsartikel (refereegranskat)abstract
- Recently, post-mortem MR quantification has been introduced to the field of post-mortem magnetic resonance imaging. By usage of a particular MR quantification sequence, T1 and T2 relaxation times and proton density (PD) of tissues and organs can be quantified simultaneously. The aim of the present basic research study was to assess the quantitative T1, T2, and PD values of regular anatomical brain structures for a 1.5T application and to correlate the assessed values with corpse temperatures. In a prospective study, 30 forensic cases were MR-scanned with a quantification sequence prior to autopsy. Body temperature was assessed during MR scans. In synthetically calculated T1, T2, and PD-weighted images, quantitative T1, T2 (both in ms) and PD (in %) values of anatomical structures of cerebrum (Group 1: frontal gray matter, frontal white matter, thalamus, internal capsule, caudate nucleus, putamen, and globus pallidus) and brainstem/cerebellum (Group 2: cerebral crus, substantia nigra, red nucleus, pons, cerebellar hemisphere, and superior cerebellar peduncle) were assessed. The investigated brain structures of cerebrum and brainstem/cerebellum could be characterized and differentiated based on a combination of their quantitative T1, T2, and PD values. MANOVA testing verified significant differences between the investigated anatomical brain structures among each other in Group 1 and Group 2 based on their quantitative values. Temperature dependence was observed mainly for T1 values, which were slightly increasing with rising temperature in the investigated brain structures in both groups. The results provide a base for future computer-aided diagnosis of brain pathologies and lesions in post-mortem magnetic resonance imaging.
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| 15. |
- Zech, Wolf-Dieter, et al.
(författare)
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Postmortem quantitative 1.5-T MRI for the differentiation and characterization of serous fluids, blood, CSF, and putrefied CSF
- 2015
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Ingår i: International journal of legal medicine. - : Springer. - 0937-9827 .- 1437-1596. ; 129:5, s. 1127-1136
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present study was to investigate whether serous fluids, blood, cerebrospinal fluid (CSF), and putrefied CSF can be characterized and differentiated in synthetically calculated magnetic resonance (MR) images based on their quantitative T (1), T (2), and proton density (PD) values. Images from 55 postmortem short axis cardiac and 31 axial brain 1.5-T MR examinations were quantified using a quantification sequence. Serous fluids, fluid blood, sedimented blood, blood clots, CSF, and putrefied CSF were analyzed for their mean T (1), T (2), and PD values. Body core temperature was measured during the MRI scans. The fluid-specific quantitative values were related to the body core temperature. Equations to correct for temperature differences were generated. In a 3D plot as well as in statistical analysis, the quantitative T (1), T (2) and PD values of serous fluids, fluid blood, sedimented blood, blood clots, CSF, and putrefied CSF could be well differentiated from each other. The quantitative T (1) and T (2) values were temperature-dependent. Correction of quantitative values to a temperature of 37 A degrees C resulted in significantly better discrimination between all investigated fluid mediums. We conclude that postmortem 1.5-T MR quantification is feasible to discriminate between blood, serous fluids, CSF, and putrefied CSF. This finding provides a basis for the computer-aided diagnosis and detection of fluids and hemorrhages.
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