Biogeographical Ancestry Estimation from Autosomal Short Tandem Repeats in the Sequencing Era

Autosomal short tandem repeats (STRs) are, and likely always will be, the first loci targeted for forensic DNA analysis as they offer the highest probability of individual identification. An ancestry-informative marker panel can then be used in “no hit, no suspect” cases, which requires additional time and cost investment, and relies on the presence of sufficient remaining sample. Traditionally this has relied on the use of specific ancestry-informative single nucleotide polymorphisms (SNPs), run as an additional test to STRs. STRs have largely been discounted for biogeographic ancestry determination due to their high mutation rate, which in turn makes them well suited for individual identification. Being able to obtain a DNA profile that can simultaneously be used both for biogeographical ancestry estimation and searching against offender databases would be of huge benefit to the field of forensic identification in terms of time, cost, and sample availability. As routine DNA testing of autosomal STRs progresses to next-generation/massively parallel sequencing, the opportunity presents itself to make use of observed sequence diversity in new ways. In particular, the presence of population-specific sequence variation raises the prospect of using STR profiles for population identification, both on their own and in combination with ancestry-informative SNPs. In this study, data were extracted from 989 samples from five global population groups prepared and sequenced using the ForenSeq DNA Signature Prep kit and the MiSeq FGx. Good differentiation between population was achieved using sequenced STR profiles, with 84% of samples classifying correctly using a conservative classification approach, and a general error rate of 3.5%—results that also showed a clear improvement over length-based data

Reply to Response to Vacuous standards – subversion of the OSAC standards-development process

This Letter to the Editor is a reply to Mohammed et al. (2021) https://doi.org/10.1016/j.fsisyn.2021.100145, which in turn is a response to Morrison et al. (2020) “Vacuous standards – subversion of the OSAC standards-development process” https://doi.org/10.1016/j.fsisyn.2020.06.005

Evaluation of DNA variants associated with androgenetic alopecia and their potential to predict male pattern baldness

Androgenetic alopecia, known in men as male pattern baldness (MPB), is a very conspicuous condition that is particularly frequent among European men and thus contributes markedly to variation in physical appearance traits amongst Europeans. Recent studies have revealed multiple genes and polymorphisms to be associated with susceptibility to MPB. In this study, 50 candidate SNPs for androgenetic alopecia were analyzed in order to verify their potential to predict MPB. Significant associations were confirmed for 29 SNPs from chromosomes X, 1, 5, 7, 18 and 20. A simple 5-SNP prediction model and an extended 20-SNP model were developed based on a discovery panel of 305 males from various European populations fitting one of two distinct phenotype categories. The first category consisted of men below 50 years of age with significant baldness and the second; men aged 50 years or older lacking baldness. The simple model comprised the five best predictors: rs5919324 near AR, rs1998076 in the 20p11 region, rs929626 in EBF1, rs12565727 in TARDBP and rs756853 in HDAC9. The extended prediction model added 15 SNPs from five genomic regions that improved overall prevalence-adjusted predictive accuracy measured by area under the receiver characteristic operating curve (AUC). Both models were evaluated for predictive accuracy using a test set of 300 males reflecting the general European population. Applying a 65% probability threshold, high prediction sensitivity of 87.1% but low specificity of 42.4% was obtained in men aged <50 years. In men aged ≥50, prediction sensitivity was slightly lower at 67.7% while specificity reached 90%. Overall, the AUC=0.761 calculated for men at or above 50 years of age indicates these SNPs offer considerable potential for the application of genetic tests to predict MPB patterns, adding a highly informative predictive system to the emerging field of forensic analysis of externally visible characteristics

A global analysis of Y-chromosomal haplotype diversity for 23 STR loci

In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.Fil: Corach, Daniel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Caputo, Mariela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Marino, Miguel Eduardo. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Laboratorio de Analisis de ADN; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Purps, Josephine. Charité-Universitätsmedizin; AlemaniaFil: Siegert, Sabine. University of Cologne; AlemaniaFil: Willuweit, Sascha. Charité-Universitätsmedizin; AlemaniaFil: Nagy, Marion. Charité-Universitätsmedizin; AlemaniaFil: Alves, Cíntia. Universidad de Porto; PortugalFil: Salazar, Renato. Universidad de Porto; PortugalFil: Angustia, Sheila M. T.. Philippine National Police Crime Laboratory; FilipinasFil: Santos, Lorna H.. Philippine National Police Crime Laboratory; FilipinasFil: Anslinger, Katja. Universitat Genzentrum Der Ludwing-maximilians; AlemaniaFil: Bayer, Birgit. Universitat Genzentrum Der Ludwing-maximilians; AlemaniaFil: Ayub, Qasim. The Wellcome Trust Sanger Institute; Reino UnidoFil: Wei, Wei. The Wellcome Trust Sanger Institute; Reino UnidoFil: Xue, Yali. The Wellcome Trust Sanger Institute; Reino UnidoFil: Tyler Smith, Chris. The Wellcome Trust Sanger Institute; Reino UnidoFil: Baeta Bafalluy, Miriam. Universidad de Zaragoza; EspañaFil: Martínez Jarreta, Begoña. Universidad de Zaragoza; EspañaFil: Egyed, Balazs. Eotvos University, Budapest; ArgentinaFil: Balitzki, Beate. Universidad de Basilea; SuizaFil: Tschumi, Sibylle. Universidad de Basilea; SuizaFil: Ballard, David. King; Reino UnidoFil: Syndercombe Court, Denise. King; Reino UnidoFil: Barrantes, Xinia. Poder Judicial, Forensic Sciences Department; Costa RicaFil: Bäßler, Gerhard. Landeskriminalamt Baden-Württemberg; AlemaniaFil: Berger, Burkhard. Universidad de Innsbruck; AustriaFil: Niederstätter, Haral. Universidad de Innsbruck; AustriaFil: Parson, Walther. Universidad de Innsbruck; Austria. University Park; Estados UnidosFil: Davis, Carey. Department of Molecular and Medical Genetics; Estados Unidos. Institute of Applied Genetics; Estados UnidosFil: Furfuro, Sandra. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Laboratorio de Análisis de ADN; ArgentinaFil: Locarno, Laura. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Laboratorio de Análisis de ADN; Argentin

African trypanosomiasis : its effect on platelet morphology, function and survival

Thrombocytopenia, occurring sometimes in conjunction with disseminated intravascular coagulation, has been reported sporadically in both human and animal trypanosomiases. The extent of the thrombocytopenia and its relationship to the anaemia and parasitaemia has been investigated in experimental infections of Trypanosoma brucei brucei and Trypanosoma congolense in rabbits, and of Trypanosoma vivax in calves. Studies of platelet size, structure, function and survival have been undertaken in an attempt to ellucidate the mechanism for the thrombocytopenia. A significant decrease in platelet number is associated with the early parasitaemia of the infection. A parasite-mediated mechanism, either immune or toxic, leads to in vivo platelet clumping, marked platelet ultrastructural changes and functional inhibition of the circulating platelets. The potential ischaemic action of the resultant microthrombi and the haemostatic problems of poorly functioning platelets may contribute significantly to the pathology of the disease. Platelet destruction, precipitated by the parasite, occurs in the spleen resulting in a reduced platelet lifespan. Experiments in asplenic animals show that other organs can take over the splenic role in this respect. Thrombocytopenic stimulation of platelet production from the increased megakaryocytic mass in the bone marrow only partially compensates for the platelet loss which continues late in the infection by a mechanism unrelated to parasite number. Evidence is provided suggesting that the expanded mononuclear phagocytic ability of the reticular endothelial system actively or passively continues the platelet destruction at this time. Support for two different mechanisms of platelet destruction, active at different stages of the disease, is also provided by experiments involving different strains of trypanosome and limited immunity experiments. The pattern of platelet destruction is similar to that suggested for red cells of an early haemolytic anaemia with a non-haemolytic anaemia active in the later stages

Discovery of potential DNA methylation markers for forensic tissue identification using bisulphite pyrosequencing

The presence of specific body fluids at crime scenes could be linked with particular types of crime, therefore attributing a DNA profile to a specific tissue could increase the evidential significance of a match with a suspect. Current methodologies such as tissue-specific mRNA profiling are useful but drawbacks include low tissue specificity and applicability to degraded samples. In this study, the potential of 11 tissue-specific differentially methylated regions, initially identified following large-scale methylation analysis of whole blood, buccal cells and sperm, was explored in order to identify markers for blood, saliva and semen. Bisulphite pyrosequencing analysis supported previous findings, but tissue-specific differentially methylated regions for blood and buccal cells did not show enough specificity to be proposed as markers for blood and saliva, respectively. For some CpGs, a large inter-individual variation in methylation levels was also observed. Two of the semen markers (cg04382920 and cg11768416) were used for further validation on a large set of stains. These two semen-specific assays showed high sensitivity (as low as 50 pg) and stability. Future experiments will shed light on the usefulness of these markers in forensic casework