Improved computations for relationship inference using low-coverage sequencing data

Pedigree inference, for example determining whether two persons are second cousins or unrelated, can be done by comparing their genotypes at a selection of genetic markers. When the data for one or more of the persons is from low-coverage next generation sequencing (lcNGS), currently available computational methods either ignore genetic linkage or do not take advantage of the probabilistic nature of lcNGS data, relying instead on first estimating the genotype. We provide a method and software (see familias.name/lcNGS) bridging the above gap. Simulations indicate how our results are considerably more accurate compared to some previously available alternatives. Our method, utilizing a version of the Lander-Green algorithm, uses a group of symmetries to speed up calculations. This group may be of further interest in other calculations involving linked loci

Subdividing Y-chromosome haplogroup R1a1 reveals Norse Viking dispersal lineages in Britain

The influence of Viking-Age migrants to the British Isles is obvious in archaeological and place-names evidence, but their demographic impact has been unclear. Autosomal genetic analyses support Norse Viking contributions to parts of Britain, but show no signal corresponding to the Danelaw, the region under Scandinavian administrative control from the ninth to eleventh centuries. Y-chromosome haplogroup R1a1 has been considered as a possible marker for Viking migrations because of its high frequency in peninsular Scandinavia (Norway and Sweden). Here we select ten Y-SNPs to discriminate informatively among hg R1a1 sub-haplogroups in Europe, analyse these in 619 hg R1a1 Y chromosomes including 163 from the British Isles, and also type 23 short-tandem repeats (Y-STRs) to assess internal diversity. We find three specifically Western-European sub-haplogroups, two of which predominate in Norway and Sweden, and are also found in Britain; starlike features in the STR networks of these lineages indicate histories of expansion. We ask whether geographical distributions of hg R1a1 overall, and of the two sub-lineages in particular, correlate with regions of Scandinavian influence within Britain. Neither shows any frequency difference between regions that have higher (≥10%) or lower autosomal contributions from Norway and Sweden, but both are significantly overrepresented in the region corresponding to the Danelaw. These differences between autosomal and Y-chromosomal histories suggest either male-specific contribution, or the influence of patrilocality. Comparison of modern DNA with recently available ancient DNA data supports the interpretation that two sub-lineages of hg R1a1 spread with the Vikings from peninsular Scandinavia

A general model for likelihood computations of genetic marker data accounting for linkage, linkage disequilibrium, and mutations

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

A universal method for species identification of mammals utilizing next generation sequencing for the analysis of DNA mixtures

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

Presumption of innocence and media rights to inform society about legal proceedings

Par nevainīguma prezumpciju var runāt kā par sākotnēju pieņēmumu, ka persona nav vainīga noziedzīga nodarījuma izdarīšanā, kamēr tās vaina nav pierādīta saskaņā ar likumu. Tomēr plašsaziņas līdzekļi, informējot sabiedrību par tiesu procesiem, bieži publicē ziņas par vienas vai otras personas “notiesāšanu” pirms šīs, patiesībā tikai iespējami vainīgās, personas saukšanas pie atbildības un notiesājoša sprieduma taisīšanas. Ievērojot minēto, darba mērķi ir noskaidrot, vai plašsaziņas līdzekļi, informējot sabiedrību par tiesas procesiem, var pārkāpt personas tiesības uz nevainīguma prezumpciju un, ja var, tad kā līdzsvarot plašsaziņas līdzekļu pienākumu informēt sabiedrību par tiesas procesiem ar citām cilvēka tiesībām. Maģistra darba ietvaros Autore secina, ka plašsaziņas līdzekļi nevar pārkāpt nevainīguma prezumpciju kā kriminālprocesu organizējošu principu, jo plašsaziņas līdzekļu izteikumi par personas vainu nevar ietekmēt kriminālprocesa norisi. Tomēr nevainīguma prezumpcijas principam nevar piešķirt tik šauru nozīmi, jo goda un cieņas, arī reputācijas aizsardzība ir viens no nevainīguma prezumpcijas aspektiem. Plašsaziņas līdzekļi var pārkāpt nevainīguma prezumpcijas reputācijas aizsardzības aspektu. Savukārt līdzsvarojot plašsaziņas līdzekļu izteikumus un nevainīguma prezumpcijas principu, Eiropas Cilvēktiesību tiesas praksē tiek vērtēti šādi kritēriji: veids, kādā informācija tika iegūta; apstrīdētā raksta saturs; raksta aktualitāte sabiedriskai diskusijai; raksta ietekme uz kriminālprocesu; privātās dzīves aizskāruma nopietnība; soda samērīgums.The presumption of innocence could be expressed as an initial presumption that a person is not guilty of a criminal offense until guilt is proven in accordance with the law. However, it has been observed that media while informing public about court proceedings often “convict” one or another person before the prosecution and conviction of that person, who is only allegedly guilty, has been made. Thus, the purposes of the Master’s thesis are to find out whether the media may violate a person's rights of the presumption of innocence by informing the public about court proceedings and, if so, how to balance the media's obligation to inform the public about court proceedings and other human rights. The author concludes that media cannot violate the presumption of innocence as a principle of criminal proceeding organization because media’s statements about guilt cannot affect the process of criminal proceedings. However, the principle of the presumption of innocence cannot be given such a narrow meaning, because the protection of honour and dignity, as well reputation, is one of the aspects of the presumption of innocence. The media may violate the reputation protection aspect of the presumption of innocence. In balancing the statements of the media and the principle of the presumption of innocence, the European Court of Human Rights assesses the following criteria: the way in which the information was obtained; the content of the impugned article; contribution of the impugned article to a public-interest debate; influence of the impugned article on the criminal proceedings; infringement of the accused’s private life; proportionality of the penalty imposed

Using X-chromosomal markers in relationship testing: Calculation of likelihood ratios taking both linkage and linkage disequilibrium into account

X-chromosomal markers in forensic genetics have become more widely used during 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 implementation of an efficient model for calculating likelihood ratios (LRs) 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\uae 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 LRs 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 used model is an efficient way of doing so

Analysis of linkage and linkage disequilibrium for eight X-STR markers

X-chromosomal short tandem repeats (X-STR) have proven to be informative and useful in complex relationship testing. Themain feature of X-STR markers, compared to autosomal forensicmarkers, 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 XSTR markers

Distribution of the number of pairwise differences (in base pairs) for the target sequence among 334 mammal species.

<p>Distribution of the number of pairwise differences (in base pairs) for the target sequence among 334 mammal species.</p

Results from experiments with DNA samples from authentic forensic cases using the 454 deep sequencing method.

<p>The number of reads obtained after analyses of five samples from authentic forensic casework are presented. Case 1 was a sample taken from a human accused of animal cruelty and case 2 was four samples taken from a human corpse with multiple bite marks.</p