Etablierung von SNaPshot-Assays zur Charakterisierung Y-chromosomaler Haplogruppen – ein Teilprojekt zur Bestimmung der Ursprungspopulation unbekannter Tatortspuren

Eine der wichtigsten Methoden in der internationalen Verbrechensbekämpfung ist die Erstellung individualspezifischer Desoxyribonukleinsäure-Profile (engl. deoxyribonucleic acid (DNA)), anhand derer Tatortspuren einem Tatverdächtigen zugeordnet werden können. Gibt es keine Hinweise auf mögliche Tatverdächtige, so kann die Ursprungspopulation einer unbekannten DNA-Spur des Tatortes für die polizeilichen Ermittlungsarbeiten von großer Bedeutung sein. Bei männlichen Spuren liefert, neben autosomalen Einzelnukleotid-Polymorphismen (engl. single nucleotide polymorphisms (SNPs)) und Polymorphismen mitochondrialer DNA (mtDNA), die Y-chromosomale Haplogruppe einen wichtigen Hinweis auf die ursprüngliche Herkunft des Spurenlegers. Sie ist über die Allelausprägung bestimmter Einzelnukleotid-Polymorphismen auf dem Y-Chromosom definiert. Das Vorkommen sowie die Verteilung solcher Haplogruppen kann in unterschiedlichen Populationen stark variieren. In dieser Studie wurden drei Minisequencing-Assays mit insgesamt 45 SNPs des Y-Chromosoms zusammengestellt und etabliert. Der Prozess der Etablierung beinhaltete das Erstellen zuverlässiger Multiplex-Polymerasekettenreaktionen-Assays (engl. polymerase chain reaction (PCR)) und SNaPshot-Multiplex-PCR-Assays, die auch geringe DNA-Mengen sowie degradierte DNA zuverlässig analysieren können. Die Kombination der Y-SNPs in den Minisequencing-Assays erlaubt eine eindeutige Zuordnung zu bestimmten, im Vorfeld ausgesuchten Y-Haplogruppen. Anschließend wurden die erstellten Minisequencing-Assays verifiziert, indem die Verteilung der Y-chromosomalen Haplogruppen in insgesamt 385 Personen aus Nordeuropa, vom Balkan, aus der Türkei, dem Nahen Osten, sowie aus Nord- und Westafrika bestimmt wurde. Dabei konnten metapopulationsspezifische Haplogruppen (Hg), wie beispielsweise Hg E1b1a für Westafrika, ermittelt werden. Es zeigte sich allerdings auch, dass andere Haplogruppen in mehreren Metapopulationen in etwa gleichen Anteilen vorkommen, wie zum Beispiel Haplogruppe J1e in Nordafrika, dem Nahen Osten und der Türkei. Anhand einiger Beispiele konnte nachgewiesen werden, dass die Y-chromosomalen Haplogruppen eine wichtige Ergänzung zur Analyse autosomaler SNPs sind

Pion-Xi correlations in Au-Au collisions at STAR

We present pion-Xi correlation analysis in Au-Au collisions at sqrt(s_NN)= 200 GeV and sqrt(s_NN) = 62.4 GeV, performed using the STAR detector at RHIC. A Xi*(1530) resonance signal is observed for the first time in Au-Au collisions. Experimental data are compared with theoretical predictions. The strength of the Xi* peak is reproduced in the correlation function assuming that pions and Xis emerge from a system in collective expansion.Comment: To appear in the proceedings of 18th Nuclear Physics Division Conference of the EPS (NPDC18),Prague, 23.8.-29.8. 200

Inclusive pi0 spectra at high transverse momentum in d-Au collisions at RHIC

Preliminary results on inclusive neutral pion production in d-Au collisions at sqrt(s_NN) = 200 GeV in the pseudo-rapidity range 0<eta<1 are presented. The measurement is performed using the STAR Barrel Electromagnetic calorimeter (BEMC). In this paper, the analysis of the first BEMC hadron measurement is described and the results are compared with earlier RHIC findings. The pi0 invariant differential cross sections show good agreement with next-to-leading order (NLO) perturbative QCD calculations.Comment: 4 pages, 5 figures, 18th Nuclear Physics Division Conference of the EPS, Prague, submitted to Nucl. Phys.

GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors

Objective: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and crossvalidated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS metaanalysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. Methods: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. Results: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values &lt;5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. Conclusions: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.</p

GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors

OBJECTIVE: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. METHODS: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. RESULTS: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values \u3c5×10 CONCLUSIONS: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe