| 1. |
- Ballantyne, Kaye N., et al.
(författare)
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Toward Male Individualization with Rapidly Mutating Y-Chromosomal Short Tandem Repeats
- 2014
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Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 35:8, s. 1021-1032
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Tidskriftsartikel (refereegranskat)abstract
- Relevant for various areas of human genetics, Y-chromosomal short tandem repeats (Y-STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17-loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality-controlled data of 13 rapidly mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, greater than99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836-0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysis of molecular variance revealed 99.98% of variation within populations, 0.018% among populations within groups, and 0.002% among groups. Of the 2,372 newly and 156 previously typed male relative pairs, 29% were differentiated including 27% of the 2,378 father-son pairs. Relative to Yfiler, haplotype diversity was increased in 86% of the populations tested and overall male relative differentiation was raised by 23.5%. Our study demonstrates the value of RMY-STRs in identifying and separating unrelated and related males and provides a reference database.
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| 2. |
- Boiso, Samuel, et al.
(författare)
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ABCB1 gene polymorphisms are associated with suicide in forensic autopsies
- 2013
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Ingår i: Pharmacogenetics & Genomics. - : Lippincott, Williams and Wilkins. - 1744-6872 .- 1744-6880. ; 23:9, s. 463-469
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Tidskriftsartikel (refereegranskat)abstract
- Background Polymorphisms in ABCB1 have the ability to affect both the function and the expression of the transporter protein P-glycoprotein and may lead to an altered response for many drugs including some antidepressants and antipsychotics.Objective The aim of this study was to examine the impact of the ABCB1 polymorphisms 1199Gandgt;A, 1236Candgt;T, 2677Gandgt;T/A, and 3435Candgt;T in deaths by suicide.Patients and methods A total of 998 consecutive Swedish forensic autopsies performed in 2008 in individuals 18 years of age or older, where femoral blood was available and a toxicological screening had been performed, were investigated. Genotypes were assessed with pyrosequencing and information on the cause and manner of each death was obtained from the forensic pathology and toxicology databases.Results There was a significantly higher frequency of the T allele at positions 1236, 2677, and 3435 among the suicide cases compared with the nonsuicide cases.Conclusion Our result from forensic cases suggests that ABCB1 polymorphisms are associated with an increased risk for completed suicides. The biological mechanisms involved and the clinical implications for these findings are largely unknown and need to be examined further.
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| 3. |
- Chaitanya, Lakshmi, et al.
(författare)
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Collaborative EDNAP exercise on the IrisPlex system for DNA based prediction of human eye colour
- 2014
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Ingår i: Forensic Science International. - : Elsevier. - 1872-4973 .- 1878-0326. ; 11, s. 241-251
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Tidskriftsartikel (refereegranskat)abstract
- The IrisPlex system is a DNA-based test system for the prediction of human eye colour from biological samples and consists of a single forensically validated multiplex genotyping assay together with a statistical prediction model that is based on genotypes and phenotypes from thousands of individuals. IrisPlex predicts blue and brown human eye colour with, on average, >94% precision accuracy using six of the currently most eye colour informative single nucleotide polymorphisms (HERC2 rs12913832, OCA2 rs1800407, SLC24A4 rs12896399, SLC45A2 (MATP) rs16891982, TYR rs1393350, and IRF4 rs12203592) according to a previous study, while the accuracy in predicting non-blue and non-brown eye colours is considerably lower. In an effort to vigorously assess the IrisPlex system at the international level, testing was performed by 21 laboratories in the context of a collaborative exercise divided into three tasks and organised by the European DNA Profiling (EDNAP) Group of the International Society of Forensic Genetics (ISFG). Task 1 involved the assessment of 10 blood and saliva samples provided on FTA cards by the organising laboratory together with eye colour phenotypes; 99.4% of the genotypes were correctly reported and 99% of the eye colour phenotypes were correctly predicted. Task 2 involved the assessment of 5 DNA samples extracted by the host laboratory from simulated casework samples, artificially degraded, and provided to the participants in varying DNA concentrations. For this task, 98.7% of the genotypes were correctly determined and 96.2% of eye colour phenotypes were correctly inferred. For Tasks 1 and 2 together, 99.2% (1875) of the 1890 genotypes were correctly generated and of the 15 (0.8%) incorrect genotype calls, only 2 (0.1%) resulted in incorrect eye colour phenotypes. The voluntary Task 3 involved participants choosing their own test subjects for IrisPlex genotyping and eye colour phenotype inference, while eye photographs were provided to the organising laboratory and judged; 96% of the eye colour phenotypes were inferred correctly across 100 samples and 19 laboratories. The high success rates in genotyping and eye colour phenotyping clearly demonstrate the reproducibility and the robustness of the IrisPlex assay as well as the accuracy of the IrisPlex model to predict blue and brown eye colour from DNA. Additionally, this study demonstrates the ease with which the IrisPlex system is implementable and applicable across forensic laboratories around the world with varying pre-existing experiences.
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| 4. |
- Egeland, Thore, et al.
(författare)
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Response to: DNA identification by pedigree likelihood ratio accommodating population substructure and mutations
- 2011
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Ingår i: Investigative Genetics. - : Springer Science and Business Media LLC. - 2041-2223. ; 2:7
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Tidskriftsartikel (refereegranskat)abstract
- Mutation models are important in many areas of genetics including forensics. This letter criticizes the model of the paper 'DNA identification by pedigree likelihood ratio accommodating population substructure and mutations' by Ge et al. (2010). Furthermore, we argue that the paper in some cases misrepresents previously published papers. Please see related letter: http://www.investigativegenetics.com/content/2/1/8.
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| 5. |
- Kling, Daniel, et al.
(författare)
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DNA microarray as a tool in establishing genetic relatedness-Current status and future prospects
- 2012
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Ingår i: Forensic Science International. - : Elsevier. - 1872-4973 .- 1878-0326. ; 6:3, s. 322-329
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Tidskriftsartikel (refereegranskat)abstract
- In the past decades, microarray technology has definitely put an edge to the field of genetic research. Our aim was to determine whether single nucleotide polymorphism (SNP) microarrays could be used as a tool in establishing genetic relationships where current molecular genetic methods are not sufficient. We used the Genechip, Affymetrix GenomeWide SNP Array 6.0, which detects more than 900,000 SNP markers dispersed throughout the human genome. The intention was to find a good selection of SNP markers that could be used for statistical evaluation of relatedness in a forensic setting. We conducted pairwise comparisons in the R-package FEST as well as pedigree comparisons in Merlin. Our methods were applied on two separate families, where relationships as distant as 3rd cousins were known. In addition, a question about a possible common ancestry between the two families was tested. Relationships as distant as 2nd cousins could be readily distinguished both from unrelated and other, genetically, closer relationships. This was achieved with a selection of 5774 markers, where each pair of markers was separated by a genetic distance of at least 0.5 cM (centiMorgan). When considering 3rd cousins, and more distant relationships, the number of markers needs to be extended, consequently decreasing the genetic distance between the markers. However, inclusion of a too large number of markers presents new challenges and our results imply that the use of too dense sets of markers always yields the highest probability for the genetically closest relationship hypothesis. Simulations confirm that this is most probably caused by the fact that the computational model assumes linkage equilibrium between markers, a problem that will be further evaluated. Our results do however suggest that SNP-data derived from microarrays are well suited for kinship determination provided linkage disequilibrium is properly accounted for.
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| 6. |
- Kling, Daniel, et al.
(författare)
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Familias 3-Extensions and new functionality
- 2014
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Ingår i: Forensic Science International. - : Elsevier. - 1872-4973 .- 1878-0326. ; 13, s. 121-127
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Tidskriftsartikel (refereegranskat)abstract
- In relationship testing the aim is to determine the most probable pedigree structure given genetic marker data for a set of persons. Disaster Victim Identification (DVI) based on DNA data from presumed relatives of the missing persons can be considered to be a collection of relationship problems. Forensic calculations in investigative mode address questions like "How many markers and reference persons are needed? Such questions can be answered by simulations. Mutations, deviations from Hardy-Weinberg Equilibrium (or more generally, accounting for population substructure) and silent alleles cannot be ignored when evaluating forensic evidence in case work. With the advent of new markers, so called microvariants have become more common. Previous mutation models are no longer appropriate and a new model is proposed. This paper describes methods designed to deal with DVI problems and a new simulation model to study distribution of likelihoods. There are softwares available, addressing similar problems. However, for some problems including DVI, we are not aware of freely available validated software. The Familias software has long been widely used by forensic laboratories worldwide to compute likelihoods in relationship scenarios, though previous versions have lacked desired functionality, such as the above mentioned. The extensions as well as some other novel features have been implemented in the new version, freely available at www.familias.no. The implementation and validation are briefly mentioned leaving complete details to Supplementary sections.
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| 7. |
- Malmström, Helena, et al.
(författare)
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Finding the founder of Stockholm - A kinship study based on Y-chromosomal, autosomal and mitochondrial DNA
- 2012
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Ingår i: Annals of Anatomy. - : Elsevier. - 0940-9602 .- 1618-0402. ; 194:1, s. 138-145
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Tidskriftsartikel (refereegranskat)abstract
- Historical records claim that Birger Magnusson (died 1266), famous regent of Sweden and the founder of Stockholm, was buried in Varnhem Abbey in Vastergotland. After being lost for centuries, his putative grave was rediscovered during restoration work in the 1920s. Morphological analyses of the three individuals in the grave concluded that the older male, the female and the younger male found in the grave were likely to be Birger, his second wife Mechtild of Holstein and his son Erik from a previous marriage. More recent evaluations of the data from the 1920s seriously questioned these conclusions, ultimately leading to the reopening and reexamination of the grave in 2002. Ancient DNA-analyses were performed to investigate if the relationship between the three individuals matched what we would expect if the individuals were Birger, Erik and Mechtild. We used pyrosequencing of Y-chromosomal and autosomal SNPs and compared the results with haplogroup frequencies of modern Swedes to investigate paternal relations. Possible maternal kinship was investigated by deep FLX-sequencing of overlapping mtDNA amplicons. The authenticity of the sequences was examined using data from independent extractions, massive clonal data, the c-statistics, and real-time quantitative data. We show that the males carry the same Y-chromosomal haplogroup and thus we cannot reject a father-son type of relation. Further, as shown by the mtDNA analyses, none of the individuals are maternally related. We conclude that the graves indeed belong to Birger, Erik and Mechtild, or to three individuals with the exact same kind of biological relatedness.
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| 8. |
- Tillmar, Andreas, et al.
(författare)
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Homogeneity in mitochondrial DNA control region sequences in Swedish subpopulations
- 2010
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Ingår i: International journal of legal medicine. - : Springer Science and Business Media LLC. - 0937-9827 .- 1437-1596. ; 124:2, s. 91-98
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Tidskriftsartikel (refereegranskat)abstract
- In order to promote mitochondrial DNA (mtDNA) testing in Sweden we have typed 296 Swedish males, which will serve as a Swedish mtDNA frequency database. The tested males were taken from seven geographically different regions representing the contemporary Swedish population. The complete mtDNA control region was typed and the Swedish population was shown to have high haplotype diversity with a random match probability of 0.5%. Almost 47% of the tested samples belonged to haplogroup H and further haplogroup comparison with worldwide populations clustered the Swedish mtDNA data together with other European populations. AMOVA analysis of the seven Swedish subregions displayed no significant maternal substructure in Sweden (F (ST) = 0.002). Our conclusion from this study is that the typed Swedish individuals serve as good representatives for a Swedish forensic mtDNA database. Some caution should, however, be taken for individuals from the northernmost part of Sweden (provinces of Norrbotten and Lapland) due to specific demographic conditions. Furthermore, our analysis of a small sample set of a Swedish Saami population confirmed earlier findings that the Swedish Saami population is an outlier among European populations.
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| 9. |
- Tillmar, Andreas O, et al.
(författare)
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A universal method for species identification of mammals utilizing next generation sequencing for the analysis of DNA mixtures
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:12, s. e83761-
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Tidskriftsartikel (refereegranskat)abstract
- Species identification can be interesting in a wide range of areas, for example, in forensic applications, food monitoring and in archeology. The vast majority of existing DNA typing methods developed for species determination, mainly focuses on a single species source. There are, however, many instances where all species from mixed sources need to be determined, even when the species in minority constitutes less than 1 % of the sample. The introduction of next generation sequencing opens new possibilities for such challenging samples. In this study we present a universal deep sequencing method using 454 GS Junior sequencing of a target on the mitochondrial gene 16S rRNA. The method was designed through phylogenetic analyses of DNA reference sequences from more than 300 mammal species. Experiments were performed on artificial species-species mixture samples in order to verify the method's robustness and its ability to detect all species within a mixture. The method was also tested on samples from authentic forensic casework. The results showed to be promising, discriminating over 99.9 % of mammal species and the ability to detect multiple donors within a mixture and also to detect minor components as low as 1 % of a mixed sample.
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| 10. |
- Tillmar, Andreas O., et al.
(författare)
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Choosing supplementary markers in forensic casework
- 2014
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Ingår i: Forensic Science International-Genetics. - : Elsevier BV. - 1872-4973 .- 1878-0326. ; 13, s. 128-133
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Tidskriftsartikel (refereegranskat)abstract
- The vast majority of human familial identifications based on DNA end up with a well founded conclusion, normally using a standard set of genetic short tandem repeat (STR) loci. There are, however, a proportion of cases that show ambiguous results. For such occasions a number of different supplementary markers could be typed in order to gain further information. There are numerous markers available for such supplementary DNA typing, including STRs, deletion and insertion polymorphisms (DIPs), and single nucleotide polymorphisms (SNPs). The purpose of this work was to describe a precise method for decision making, aiming to aid the comparison of different sets of markers for different case scenarios in order to find the most efficient set for routine casework. Comparisons are based on a particular function relating the expected additional value of information from new data to the amount of information already obtained from initial data. The function can be computed approximately by approximating likelihood-based error rates using simulation. In this paper we focused on paternity investigations, more specifically the use of supplementary markers in cases where a smaller number of genetic inconsistencies make the matter inconclusive. We applied the method to a comparison of three different kits: Investigator HDplex (STRs), Investigator DIPplex (DIPs), and the SNPforID-plex (SNPs) to study their efficiencies in gaining information in different case scenarios involving various alternative relationships between the tested man and the tested child. We show that the Investigator HDplex was the most efficient set of supplementary markers for the standard paternity case. However, for paternity cases with a close relative being the alternative father, the Investigator HDplex and the SNPforID-plex showed similar patterns in their ability to deliver a well-founded conclusion. The Investigator DIPplex was the least efficient set.
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