| 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. |
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| 3. |
- Egeland, Thore, et al.
(författare)
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Beyond traditional paternity and identification cases: Selecting the most probable pedigree
- 2000
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Ingår i: Forensic Science International. ; 110:1, s. 47-59
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Tidskriftsartikel (refereegranskat)abstract
- The paper extends on the traditional methodology used to quantify DNA evidence in paternity or identificationcases. By extending we imply that there are more than two alternatives to choose between. In a standard paternitycase the two competing explanations H1: “John Doe is the father of the child” and H2: “A random man is the father of the child”, are typically considered. A paternity index of 100 000 implies that the data is 100 000 more likely assuming hypothesis H1 rather than H2. If H2 is replaced by “A brother of John Doe is the father”, the LR may change dramatically. The main topic of this paper is to determine the most probable pedigree given a certain set of data including DNA profiles. In the previous example this corresponds to determining the most likely relation between John Doe and the child. Based on DNA obtained from victims of a fire, bodies found in an ancient grave or from individuals seeking to confirm their anticipated family relations, we would like to determine the most probable pedigree. The approach we present provides the possibility to combine non-DNA evidence, say age of individuals, and DNA profiles. The program familias, obtainable as shareware from http://www.nr.no/familias, delivers the probabilities for the various family constellations. More precisely, the information (if any) prior to DNA is combined with the DNA-profiles in a Bayesian manner to deliver the posterior probabilities. We exemplify using the well published Romanov data where the accepted solution emerges among 4536 possibilities considered. Various other applications based on forensic case work are discussed. In addition we have simulated data to resemble an incest case. Since the true family relation is known in this case, we may evaluate the method.
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| 4. |
- Egeland, Thore, et al.
(författare)
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Beyondtraditionalpaternity and identificationcases: Selecting the most probable pedigree
- 2002
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Ingår i: Forensic Science International. ; 110:1, s. 47-59
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Tidskriftsartikel (refereegranskat)abstract
- The paper extends on the traditional methodology used to quantify DNA evidence in paternity or identificationcases. By extending we imply that there are more than two alternatives to choose between. In a standard paternitycase the two competing explanations H1: “John Doe is the father of the child” and H2: “A random man is the father of the child”, are typically considered. A paternity index of 100000 implies that the data is 100000 more likely assuming hypothesis H1 rather than H2. If H2 is replaced by “A brother of John Doe is the father”, the LR may change dramatically. The main topic of this paper is to determine the most probable pedigree given a certain set of data including DNA profiles. In the previous example this corresponds to determining the most likely relation between John Doe and the child. Based on DNA obtained from victims of a fire, bodies found in an ancient grave or from individuals seeking to confirm their anticipated family relations, we would like to determine the most probable pedigree. The approach we present provides the possibility to combine non-DNA evidence, say age of individuals, and DNA profiles. The program familias, obtainable as shareware from http://www.nr.no/familias, delivers the probabilities for the various family constellations. More precisely, the information (if any) prior to DNA is combined with the DNA-profiles in a Bayesian manner to deliver the posterior probabilities. We exemplify using the well published Romanov data where the accepted solution emerges among 4536 possibilities considered. Various other applications based on forensic case work are discussed. In addition we have simulated data to resemble an incest case. Since the true family relation is known in this case, we may evaluate the method.
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| 5. |
- Egeland, Thore, et al.
(författare)
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Estimating the number of contributors to a DNA profile
- 2003
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Ingår i: International Journal of Legal Medicine. ; 117:5, s. 271-275
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Tidskriftsartikel (refereegranskat)abstract
- The broad topic of this paper is the evaluation of DNA evidence in criminal cases. More specifically, we deal with mixture evidence which refers to cases where there are, or could be, several contributors to a biological stain based on, e.g., blood or semen. The present paper adresses DNA mixtures based on single nucleotide polymorphism (SNP) markers, i.e., diallelic markers. Based on STR analysis, it is in most cases easy to identify the presence of a mixture since three or four bands will show up with a high probability for at least one locus. Obviously, this will not be the case for diallelic markers and interpreting mixtures will be a great challenge. We address this problem by first approaching the more general problem of estimating the number of contributors to a stain. In addition we discuss how the markers should be selected and how many are required.
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| 6. |
- Egeland, Thore, et al.
(författare)
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Relationship Inference with Familias and R
- 2016
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Relationship Inference in Familias and R discusses the use of Familias and R software to understand genetic kinship of two or more DNA samples. This software is commonly used for forensic cases to establish paternity, identify victims or analyze genetic evidence at crime scenes when kinship is involved. The book explores utilizing Familias software and R packages for difficult situations including inbred families, mutations and missing data from degraded DNA. The book additionally addresses identification following mass disasters, familial searching, non-autosomal marker analysis and relationship inference using linked markers. The second part of the book focuses on more statistical issues such as estimation and uncertainty of model parameters. Although written for use with human DNA, the principles can be applied to non-human genetics for animal pedigrees and/or analysis of plants for agriculture purposes. The book contains necessary tools to evaluate any type of forensic case where kinship is an issue.
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| 7. |
- 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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| 8. |
- Egeland, Thore, et al.
(författare)
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Statistical Genetics and Genetical Statistics: a Forensic Perspective
- 2002
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Ingår i: Scandinavian Journal of Statistics. ; 29:2, s. 297-307
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Tidskriftsartikel (refereegranskat)abstract
- This review paper focuses on forensic aspects of the relation between statistics and genetics. Some of the scientific achievements of the Swedish psychiatrist and geneticist Erik Essen-Möller may be viewed in the above interdisciplinary context. In a number of situations the correct familial relation between a group of individuals is required. We discuss recent work done to relax some assumptions involved in the classical calculations in Essen-Möller (1938). Moreover, we extend the discussion to identification problems. In a given case there may be a large number of possible family constellations or pedigrees. A prior probability distribution is established. The posterior model accounts for the combinatorial complexities of the pedigrees, mutations, kinship, and uncertainty in allele frequencies. Examples are based on the shareware program FAMILIAS, see http://www.nr.no/familias. A main message of the present paper is that the Bayesian approach is a convenient framework to down-weight unreasonable (e.g. incestuous) pedigrees that may always appear likely if only DNA-measurements are used.
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| 9. |
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| 10. |
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| 11. |
- 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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| 12. |
- 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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| 13. |
- Kling, Daniel, et al.
(författare)
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Using Object Oriented Bayesian Networks to Model Linkage, Linkage Disequilibrium and Mutations between STR Markers
- 2012
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Ingår i: PloS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:9
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Tidskriftsartikel (refereegranskat)abstract
- In a number of applications there is a need to determine the most likely pedigree for a group of persons based on genetic markers. Adequate models are needed to reach this goal. The markers used to perform the statistical calculations can be linked and there may also be linkage disequilibrium (LD) in the population. The purpose of this paper is to present a graphical Bayesian Network framework to deal with such data. Potential LD is normally ignored and it is important to verify that the resulting calculations are not biased. Even if linkage does not influence results for regular paternity cases, it may have substantial impact on likelihood ratios involving other, more extended pedigrees. Models for LD influence likelihoods for all pedigrees to some degree and an initial estimate of the impact of ignoring LD and/or linkage is desirable, going beyond mere rules of thumb based on marker distance. Furthermore, we show how one can readily include a mutation model in the Bayesian Network; extending other programs or formulas to include such models may require considerable amounts of work and will in many case not be practical. As an example, we consider the two STR markers vWa and D12S391. We estimate probabilities for population haplotypes to account for LD using a method based on data from trios, while an estimate for the degree of linkage is taken from the literature. The results show that accounting for haplotype frequencies is unnecessary in most cases for this specific pair of markers. When doing calculations on regular paternity cases, the markers can be considered statistically independent. In more complex cases of disputed relatedness, for instance cases involving siblings or so-called deficient cases, or when small differences in the LR matter, independence should not be assumed. (The networks are freely available at http://arken.umb.no/~dakl/BayesianNetworks.)
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| 14. |
- Mostad, Petter, 1964, et al.
(författare)
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The Quest for a Donor: Probability Based Methods Offer Help.
- 2005
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- When a patient in need of a stem cell transplant has no compatible donor within his or herclosest family, and no matched unrelated donor can be found, a remaining option is to searchwithin the patient’s extended family. This situation often arises when the patient is of anethnic minority, originating from a country that lacks a well-developed stem cell donorprogram, and has HLA haplotypes that are rare in his or her country of residence. Searchingwithin the extended family may be time-consuming and expensive, and tools to calculate theprobability of a match within groups of untested relatives would facilitate the search.We present a general approach to calculating the probability of a match in a given relative, orgroup of relatives, based on the pedigree, and on knowledge of the genotypes of some of theindividuals. The method extends previous approaches by allowing the pedigrees to beconsanguineous and arbitrarily complex, with deviations from Hardy-Weinberg equilibrium.We show how this extension has a considerable effect on results, in particular for rarehaplotypes. The methods are exemplified using freeware programs to solve a case of practicalimportance.
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| 15. |
- Mostad, Petter, 1964, et al.
(författare)
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Variogram estimation in a Bayesian framework
- 1999
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Ingår i: Geostatistics Wollongong 96 - Proceedings of the Fifth International Geostatistics Congress, Wollongong, Australia, September 1996.
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Konferensbidrag (refereegranskat)
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| 16. |
- Svennblad, Bodil, 1966-
(författare)
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On Estimating Topology and Divergence Times in Phylogenetics
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This PhD thesis consists of an introduction and five papers, dealing with statistical methods in phylogenetics.A phylogenetic tree describes the evolutionary relationships among species assuming that they share a common ancestor and that evolution takes place in a tree like manner. Our aim is to reconstruct the evolutionary relationships from aligned DNA sequences.In the first two papers we investigate two measures of confidence for likelihood based methods, bootstrap frequencies with Maximum Likelihood (ML) and Bayesian posterior probabilities. We show that an earlier claimed approximate equivalence between them holds under certain conditions, but not in the current implementations of the two methods.In the following two papers the divergence times of the internal nodes are considered. The ML estimate of the divergence time of the root is improved if longer sequences are analyzed or if more taxa are added. We show that the gain in precision is faster with longer sequences than with more taxa. We also show that the algorithm of the software package PATHd8 may give biased estimates if the global molecular clock is violated. A change of the algorithm to obtain unbiased estimates is therefore suggested.The last paper deals with non-informative priors when using the Bayesian approach in phylogenetics. The term is not uniquely defined in the literature. We adopt the idea of data translated likelihoods and derive the so called Jeffreys' prior for branch lengths using Jukes Cantor model of evolution.
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| 17. |
- Thelle, Dag, 1942, et al.
(författare)
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Genetisk epidemiologi
- 2007
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Ingår i: Epidemiologiske og kliniske forskningsmetoder. - 8205335052 ; , s. 463-498
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 18. |
- Thore, Egeland, et al.
(författare)
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Relationship Inference with Familias and R : Statistical Methods in Forensic Genetics
- 2016
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- Relationship Inference in Familias and R discusses the use of Familias and R software to understand genetic kinship of two or more DNA samples. This software is commonly used for forensic cases to establish paternity, identify victims or analyze genetic evidence at crime scenes when kinship is involved. The book explores utilizing Familias software and R packages for difficult situations including inbred families, mutations and missing data from degraded DNA. The book additionally addresses identification following mass disasters, familial searching, non-autosomal marker analysis and relationship inference using linked markers. The second part of the book focuses on more statistical issues such as estimation and uncertainty of model parameters. Although written for use with human DNA, the principles can be applied to non-human genetics for animal pedigrees and/or analysis of plants for agriculture purposes. The book contains necessary tools to evaluate any type of forensic case where kinship is an issue.
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| 19. |
- Tillmar, Andreas, et al.
(författare)
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Analysis of linkage and linkage disequilibrium for eight X-STR markers.
- 2008
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Ingår i: Forensic science international. Genetics. - : Elsevier. - 1878-0326 .- 1872-4973. ; 3:1, s. 37-41
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Tidskriftsartikel (refereegranskat)abstract
- X-chromosomal short tandem repeats (X-STR) have proven to be informative and useful in complex relationship testing. The main feature of X-STR markers, compared to autosomal forensic markers, is that all loci are located on the same chromosome. Thus, linkage and linkage disequilibrium may occur. The aim of this work was to study population genetic parameters of eight X-STR markers, located in four linkage groups. We present haplotype frequencies, based on 718 Swedish males, for the four linkage groups included in the Argus X-8 kit. Forensic efficiency parameters have been calculated as well as the allelic association between the tested markers for detection of linkage disequilibrium. To study the occurrences of recombination between the loci, both Swedish and Somali families were typed. A mathematical model for the estimation of recombination frequencies is presented and applied on the family samples. Our study showed that the tested markers all have highly informative forensic values and that there is a significant degree of linkage disequilibrium between the STR markers within the four linkage groups. Furthermore, based on the tested families, we also demonstrated that two of the linkage groups are partially linked. A consequence of these findings is that both linkage and linkage disequilibrium should be accounted for when producing likelihood ratios in relationship testing with X-STR markers.
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| 20. |
- Tillmar, Andreas, et al.
(författare)
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DNA Commission of the International Society for Forensic Genetics ( ISFG): Guidelines on the use of X-STRs in kinship analysis
- 2017
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Ingår i: Forensic Science International. - : ELSEVIER IRELAND LTD. - 1872-4973 .- 1878-0326. ; 29, s. 269-275
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Tidskriftsartikel (refereegranskat)abstract
- Forensic genetic laboratories perform an increasing amount of genetic analyses of the X chromosome, in particular to solve complex cases of kinship analysis. For some biological relationships X-chromosomal markers can be more informative than autosomal markers, and there are a large number of markers, methods and databases that have been described for forensic use. Due to their particular mode of inheritance, and their physical location on a single chromosome, some specific considerations are required when estimating the weight of evidence for X-chromosomal marker DNA data. The DNA Commission of the International Society for Forensic Genetics (ISFG) hereby presents guidelines and recommendations for the use of X-chromosomal markers in kinship analysis with a special focus on the biostatistical evaluation. Linkage and linkage disequilibrium (association of alleles) are of special importance for such evaluations and these concepts and the implications for likelihood calculations are described in more detail. Furthermore it is important to use appropriate computer software that accounts for linkage and linkage disequilibrium among loci, as well as for mutations. Even though some software exist, there is still a need for further improvement of dedicated software. (C) 2017 Elsevier B.V. All rights reserved.
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| 21. |
- Tillmar, Andreas, 1980-, et al.
(författare)
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Using X-chromosomal markers in relationship testing: How to calculate likelihood ratios taking linkage and linkage disequilibrium into account
- 2011
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Ingår i: Forensic Science International. - : Elsevier. - 1872-4973 .- 1878-0326. ; 5:5, s. 506-511
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Tidskriftsartikel (refereegranskat)abstract
- X-chromosomal markers in forensic genetics have become more widely used during the recent years, particularly for relationship testing. Linkage and linkage disequilibrium (LD) must typically be accounted for when using close X-chromosomal markers. Thus, when producing the weight-of-evidence, given by a DNA-analysis with markers that are linked, the normally used product rule is invalid. Here we present an efficient model for calculating likelihood ratio (LR) with markers on the X-chromosome which are linked and in LD. Furthermore, the model was applied on several cases based on data from the eight X-chromosomal loci included in the Mentype® Argus X-8 (Biotype). Using a simulation approach we showed that the use of X-chromosome data can offer valuable information for choosing between the alternatives in each of the cases we studied, and that the LR can be high in several cases. We demonstrated that when linkage and LD were disregarded, as opposed to taken into account, the difference in calculated LR could be considerable. When these differences were large, the estimated haplotype frequencies often had a strong impact and we present a method to estimate haplotype frequencies. Our conclusion is that linkage and LD should be accounted for when using the tested set of markers, and the presented model is an efficient way of doing so.
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