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Die Erstellung von Abstammungsgutachten bei Vorliegen der haufigen Triokonstellation, bestehend aus Mutter, Kind und Putativvater, ist im Normalfall mit der Typisierung von „short tandem repeats“ der Autosomen problemlos moglich und benotigt nur in Ausnahmefallen die Analyse gonosomaler Marker. X-chromosomale Marker leisten v. a. zur Losung von Defizienzgutachten einen wertvollen Beitrag. Die Anwendbarkeit ist allerdings nur gegeben, wenn X-chromosomale Vererbungslinien vorliegen. Mit der Methode der X-chromosomalen Haplotypisierung lassen sich auch weit entfernte Verwandtschaftsverhaltnisse wie Tante/Nichte oder Cousins und Cousinen ersten Grades nachweisen. Weil mannliche Individuen nur ein Chromosom X besitzen, offenbart die Typisierung der X-chromosomalen Marker hier direkt den X-chromosomalen Haplotyp. Die Haplotypenkonstellation im weiblichen Geschlecht lasst sich oft aus der Stammbaumanalyse ableiten. Die X-chromosomale Analyse kann auch besonders wirkungsvoll zur Losung von Verwandtschafts- und Inzestfallen eingesetzt werden. In der forensischen Spurenkunde ist die X-chromosomale Analyse von Vorteil, wenn weibliche Spuren in einer mannlichen Kontamination identifiziert werden sollen. Bei der Arbeit mit X-chromosomalen Markern ist eine Reihe von ethischen Aspekten zu beachten.

Im Verlauf der letzten beiden Jahre fiel im Raum Magdeburg und Umgebung eine augenscheinliche Haufung von todlichen Kohlenstoffmonoxid- (CO-)Intoxikationen durch das Betreiben von Holzkohlegrills in geschlossenen Raumen auf. In einem experimentellen Ansatz wurde die Entwicklung der CO-Konzentrationen wahrend der Verbrennung unterschiedlicher Materialien (Holzkohle, Grillbriketts, Bambus Cook Chips) im Rahmen eines Grillvorgangs in einem geschlossenen Container gemessen. Die resultierenden Gaskonzentrationen sowie die Temperaturen im Raum und in der Glut wurden aufgezeichnet. Dabei wurden im Container CO-Konzentrationen erreicht, die den Tod in Abhangigkeit von den Randbedingungen (Art der Grillkohle, Menge und Zustand der Restglut) nach etwa 30–60 min eintreten lassen konnen. Insbesondere bei Verwendung eines Indoor-Grills ist nach einer Betriebszeit von 60 min mit dem Auftreten von gesundheitlich kritischen Situationen zu rechnen. Die Ergebnisse wurden dem Bundesministerium fur Ernahrung, Landwirtschaft und Verbraucherschutz mitgeteilt, um langfristig eine Risikominimierung hinsichtlich der Todesursache „CO-Intoxikation durch Betreiben eines Grills im geschlossenen Raum“, z. B. mithilfe eines entsprechenden auffalligen Warnhinweises auf den Grillkohleverpackungen, zu erreichen.

In this study a set of 29 X-chromosomal short tandem repeats (STRs) located within the Xq26 region was evaluated. These STRs were found within the 133.14–133.45 Mb region around the HPRTB locus. Evaluation of the microsatellites was performed with regard to polymorphism, reliable amplification, and low stutter artefacts. DXS10101, DXS10102, and DXS10103 were identified as those X-STRs with highest diversity; i.e. PIC values of 0.7174–0.8933. The locus DXS10101 was the optimal candidate for the integration in the commercial available test system Mentype Argus X-8 PCR amplification kit.

The evaluation of four pairs of tightly linked chromosome X (ChrX) short tandem repeat (STR)s at Xp22, Xq12, Xq26 and Xq28 led to the creation of the Argus X 8 multiplex amplification kit. These eight STRs are distributed as four closely linked pairs over the entire X-chromosome, and for practical reasons, they are assigned to four linkage groups 1-4. To achieve a further considerable enhancement in discrimination power, we suggest to include additional markers. A recent paper referred to the earlier evaluation of STR clusters at Xq12, Xq26 and Xq28, and here we present the pending data of linkage group 1 at Xp22. The newly established STR updates the Xp22 STR cluster which now presents three polymorphic markers: DXS10148 (PIC = 0.8556), DXS10135 (PIC = 0.9093) and DXS 8378 (PIC = 0.6454). Typing of 398 X-chromosomes provided 278 different and 200 unique haplotypes. All the other haplotypes observed appeared with frequencies in the range between 0.005 and 0.015. Considering this STR triple in the context with the three further triple clusters Xq12, Xq26 and Xq28 published earlier, we announced the development of a next generation of a ChrX STR cluster typing kit.

The evaluation of the short tandem repeat (STR) markers DXS10079, DXS10074 and DXS10075 was amended to establish a STR cluster spanning a genetic distance

Daten aus konservativen erkennungsdienstlichen Masnahmen konnen ohne Richtervorbehalt auch bei minder schweren Straftaten erhoben und gespeichert werden. Hierbei werden Personaldaten und auserlich erkennbare Merkmale dokumentiert. Obligate Fotos lassen ethnische Zugehorigkeiten, Korperbautypen und Krankheitssymptome zu erkennen. Die Daktyloskopie liefert mit Hilfe der „Dermatoglyphic-Methode“ ebenfalls Hinweise auf schwere Erbleiden (Down-Syndrom u.v.a.m). Mit dem DNS-Identifizierungsmuster werden 8 nichtkodierende autosomale Lozi und das Kerngeschlecht am Amelogeninort bestimmt. Insgesamt offenbart das DNS-Identifizierungsmuster wesentlich weniger personlichkeitsrelevante Informationen als die anderen Methoden. Der Eingriff in die Personlichkeit ist bei den konservativen Masnahmen wesentlich groser. Es gibt keine Argumente fur eine juristische Ungleichbehandlung der verschiedenen erkennungsdienstlichen Masnahmen, sowohl in Bezug auf den Richtervorbehalt als auch auf den Straftatenkatalog. Allerdings muss das Probenvernichtungsgebot kontrollierbar eingehalten werden.

Short tandem repeat (STR) markers DXS6801 (GATA41B11), DXS6809 (GATA69B129) and DXS6789 (GATA31F01) are located in a 3-Mb region on human chromosome Xq21, spanning approximately 3-6 cM. Theoretically, this cluster could give rise to 1,144 different haplotypes in the German population. In fact, genotyping of 806 males revealed the presence of 207 different haplotypes. Since the three STRs have been shown to be in strong linkage disequilibrium (LD), haplotype frequencies cannot be computed on the basis of single locus allele frequencies alone, but have to be estimated directly instead. In this work, we present data on linkage, haplotype frequencies and LD in the German population. To highlight the potential of the STR cluster for forensic analysis, we also report two examples of its successful application in pedigree-based kinship testing.

To test for human population substructure and to investigate human population history we have analysed Y-chromosome diversity using seven microsatellites (Y-STRs) and ten binary markers (Y-SNPs) in samples from eight regionally distributed populations from Poland (n = 913) and 11 from Germany (n = 1,215). Based on data from both Y-chromosome marker systems, which we found to be highly correlated (r = 0.96), and using spatial analysis of the molecular variance (SAMOVA), we revealed statistically significant support for two groups of populations: (1) all Polish populations and (2) all German populations. By means of analysis of the molecular variance (AMOVA) we observed a large and statistically significant proportion of 14% (for Y-SNPs) and 15% (for Y-STRs) of the respective total genetic variation being explained between both countries. The same population differentiation was detected using Monmonier's algorithm, with a resulting genetic border between Poland and Germany that closely resembles the course of the political border between both countries. The observed genetic differentiation was mainly, but not exclusively, due to the frequency distribution of two Y-SNP haplogroups and their associated Y-STR haplotypes: R1a1*, most frequent in Poland, and R1*(xR1a1), most frequent in Germany. We suggest here that the pronounced population differentiation between the two geographically neighbouring countries, Poland and Germany, is the consequence of very recent events in human population history, namely the forced human resettlement of many millions of Germans and Poles during and, especially, shortly after World War II. In addition, our findings have consequences for the forensic application of Y-chromosome markers, strongly supporting the implementation of population substructure into forensic Y chromosome databases, and also for genetic association studies.

Inzest ist definiert als heterosexueller Verkehr zwischen Blutsverwandten, die durch unmittelbare gemeinsame Abstammung 25% oder mehr gemeinsame Gene aufweisen. Bei weniger enger Verwandtschaft spricht man von Konsanguinitat. Das Risiko fur das Auftreten genetisch bedingter Erkrankungen ist drastisch erhoht. In den grosen Weltreligionen ist ein Inzestverbot fest verankert. In nahezu allen menschlichen Gesellschaften der Gegenwart und der Vergangenheit ist und war Inzest geachtet und bei Strafe verboten. Soziologische Untersuchungen deuten darauf hin, dass das Inzesttabu bereits als kindliche Pragung ausgebildet ist (Westermarck-Effekt). Neuere Ergebnisse beweisen, dass eine Inzestvermeidung auch im Tierreich ausgepragt ist, und dass die biologische Determiniertheit wahrscheinlich auch fur den Menschen zutrifft. Trotzdem kommt Inzest in allen menschlichen Gesellschaften vor und beschaftigt Psychotherapeuten, Jurisprudenz und Rechtsmedizin. Im Folgenden werden u. a. 3 Abstammungsfalle mit Inzestverdacht vorgestellt.

The first and second hypervariable regions of the human mitochondrial DNA control region contain two homopolymeric stretches of cytosine (nt 16184–16193 and nt 303–315, respectively). According to the Cambridge reference sequence these homopolymeric stretches are interrupted by thymine (T), at positions 16189 and 310, respectively. Monotonous runs of the same base have been suggested to be hot spots for mutations, probably caused by replication slippage, resulting in length heteroplasmy. This paper describes a rapid method based on restriction cleavage of labelled PCR products encompassing the homopolymeric tract in HVII to quantify the relative proportions of different length variants present in an individual. To compare the accuracy of this method, cloned PCR products from several heteroplasmic individuals have been additionally sequenced.

The incorporation of reference DNA is crucial to the validation of any DNA typing protocol. This paper aims to provide a panel of reference DNAs for actual forensic profiling strategies, i.e. autosomal and gonosomal STR typing as well as mtDNA sequencing. We have characterised three human lymphoid cell lines, GM9947, GM9948 and GM3657, and considered 58 autosomal and gonosomal microsatellites as well as the mitochondrial control region sequence. Well-established markers and STRs recently developed for forensic use were involved. K562 DNA samples which we purchased from two different suppliers were also analysed. They revealed conflicting results with regard to the ChrX STR marker genotype. Hence, we suggest that K562 is no longer used for the calibration of profiling techniques. Our investigation establishes a panel of one female and two male DNA samples as an STR allelic ladder calibration tool and offers information on six alleles of each autosome (AS) marker, three alleles of each X chromosome (ChrX) marker and two alleles of each ChrY marker. In addition, sequences of the mitochondrial control region of the three DNAs are communicated in order to provide sequencing quality control.

This paper presents an example of deficiency paternity testing by using 15 chromosome X (ChrX) markers. The special power of ChrX typing in deficiency kinship testing is demonstrated. In the case of investigation, ChrX haplotyping confirmed the claim of the disputed offspring to be related to the deceased putative father.

In some special cases of post-mortem identification and deficiency paternity testing, the investigation of X-chromosome (ChrX) markers may be more informative than the investigation of autosomal polymorphisms. We analysed the trinucleotide repeat polymorphism DXS7424 (GDB-G00-577-633), cytogenetically mapped at Xq22. PCR fragment length measurements, sequencing and linkage studies were carried out. In a sample of 474 unrelated Germans, we found 12 alleles with the regular repeat structure (TAA)[9–20]. The population sample was characterised by the following features: polymorphism information content (PIC)=0.776; heterozygosity (Het)=0.836; mean exclusion chance (MEC)=0.762. Kinship tests revealed a typical X-linked inheritance without any mutation. Significant deviations from the Hardy–Weinberg equilibrium (HWE) were not established. Linkage studies confirmed close linkage to DXS101. It was not possible to exclude linkage disequilibrium between DXS101 and DXS7424 through haplotyping of 390 male individuals.

We examined the mitochondrial (mt) loci nt00073 and nt16519 which show a considerable variability among European populations. These polymorphisms are easily detectable by means of PCR-based RFLP analysis. The study was also aimed at establishing the Light Cycler™ technique for application to forensic mt analysis. In analysing the loci nt00073 and nt16519, both methods provide very easy access and yield compatible results. We found that nt00073 is highly variable in German and Syrian populations and fairly homogeneous among Vietnamese, Japanese, Peruvians and Cameroonians. Locus nt16519 is highly variable in all populations investigated. However, in contrast to nt00073, its contribution to the mitochondrial potential for discriminating between various ethnic populations is rather negligible.

Die kombinierte Anwendung genetischer Marker in der forensischen Spurenkunde und im Abstammungsnachweis erfordert eine genaue Kenntnis deren Lokalisation. Das Ubersichtsreferat lokalisiert die forensischen Marker zytogenetisch und genetisch in den Ideogrammen der 22 Autosomen. Diesbezugliche Informationen wurden aus Gendatenbanken zusammengetragen, die ohne Zugangsbeschrankungen im World Wide Web aufgesucht werden konnen. Es fanden Marker Berucksichtigung, die mittels Medline fur den Zeitraum von 1990 bis 06/2001 aus den Zeitschrifen Int J Legal Med, J Forensic Sci und Forensic Sci Int herausgefiltert werden konnten. Auch Marker, die im gleichen Zeitraum in den Proceedings der ISFG (vormals ISFH) genannt worden sind, wurden aufgenommen.

Allele frequencies for 16 X-linked STRs, suitable for forensic purposes, were obtained from a sample of unrelated German individuals (male and female), The presented data show also repeat sequence structures and statistic parameters describing there information content.

The reference database of highly informative Y-chromosomal short tandem repeat (STR) haplotypes (YHRD), available online at http://ystr.charite.de, represents the largest collection of male-specific genetic profiles currently available for European populations. By September 2000, YHRD contained 4688 9-locus (so-called "minimal") haplotypes, 40% of which have been extended further to include two additional loci. Establishment of YHRD has been facilitated by the joint efforts of 31 forensic and anthropological institutions. All contributing laboratories have agreed to standardize their Y-STR haplotyping protocols and to participate in a quality assurance exercise prior to the inclusion of any data. In view of its collaborative character, and in order to put YHRD to its intended use, viz. the support of forensic caseworkers in their routine decision-making process, the database has been made publicly available via the Internet in February 2000. Online searches for complete or partial Y-STR haplotypes from evidentiary or non-probative material can be performed on a non-commercial basis, and yield observed haplotype counts as well as extrapolated population frequency estimates. In addition, the YHRD website provides information about the quality control test, genotyping protocols, haplotype formats and informativity, population genetic analysis, literature references, and a list of contact addresses of the contributing laboratories.

A 9-locus microsatellite framework (minimal haplotype), previously developed for forensic purposes so as to facilitate stain analysis, personal identification and kinship testing, has been adopted for the establishment of a large reference database of male European Y-chromosomal haplotypes. The extent of population stratification pertaining to this database, an issue crucial for its practical forensic application, was assessed through analysis of molecular variance (AMOVA) of the 20 regional samples included. Despite the notion of some significant haplotype frequency differences, which were found to correlate with known demographic and historic features of Europeans, AMOVA generally revealed a high level of genetic homogeneity among the populations analyzed. Owing to their high diversity, however, accurate frequency estimation is difficult for Y-STR haplotypes when realistic (i.e. moderately sized) datasets are being used. As expected, strong pair-wise and higher order allelic associations were found to exist between all markers studied, implying that haplotype frequencies cannot be estimated as products of allele frequencies. A new extrapolation method was therefore developed which treats haplotype frequencies as random variables and generates estimates of the underlying distribution functions on the basis of closely related haplotypes. This approach, termed frequency ‘surveying’, is based upon standard population genetics theory and can in principle be applied to any combination of markers located on the Y-chromosome or in the mitochondrial genome. Application of the method to the quality assured reference Y-STR haplotype database described herein will prove very useful for the evaluation of positive trace-donor matches in forensic casework.

The paper presents results of forensic mitochondrial DNA analyses which were aimed at typing the traces caused by touching or abrasion of skin cells. Five cases of strangulation tool investigation are summarised. Two cases of homicide could be cleared up by identifying the mtDNA of both the victim and the suspect on cables which had obviously been used as strangulation tools. In eight of 10 cases, weapons could be reliably assigned to their users. The mtDNA of the users could be even detected on cartridges after firing. In one case, evidence of a suicide could be provided by means of mtDNA sequencing of the wiping traces on a suicide note.

A number of applications of analysis of human Y-chromosome microsatellite loci to human evolution and forensic science require reliable estimates of the mutation rate and knowledge of the mutational mechanism. We therefore screened a total of 4,999 meioses from father/son pairs with confirmed paternity (probability >/=99. 9%) at 15 Y-chromosomal microsatellite loci and identified 14 mutations. The locus-specific mutation-rate estimates were 0-8. 58x10-3, and the average mutation rate estimates were 3.17x10-3 (95% confidence interval [CI] 1.89-4.94x10-3) across 8 tetranucleotide microsatellites and 2.80x10-3 (95% CI 1.72-4.27x10-3) across all 15 Y-chromosomal microsatellites studied. Our data show a mutational bias toward length increase, on the basis of observation of more repeat gains than losses (10:4). The data are in almost complete agreement with the stepwise-mutation model, with 13 single-repeat changes and 1 double-repeat change. Sequence analysis revealed that all mutations occurred in uninterrupted homogenous arrays of >/=11 repeats. We conclude that mutation rates and characteristics of human Y-chromosomal microsatellites are consistent with those of autosomal microsatellites. This indicates that the general mutational mechanism of microsatellites is independent of recombination.

This study continues earlier attempts to establish linked locus STR clusters at several ChrX areas for usage in kinship testing. The three polymorphic X-chromosomal STR markers DXS10146, DXS10134 and DXS10147 are already known as linkage group within a 79.1kb region in Xq28. Additionally, the closely linked STR DXS7423 was included into the study of the Xq28 cluster spanning a region of 126.6kb. Allele and haplotype frequencies of a German and Ethiopian population were reported and compared. Typing this cluster in a German population of 404 males 311 different haplotypes were found. Genotyping of 102 men from Ethiopian population revealed the presence of 96 haplotypes. Recombination analysis was performed in 109 father–daughter–grandson trios in which two crossing over events were observed located in the 65.8kb region between DXS10134 and DXS10146. Using this STR complex for haplotyping in kinship testing further genetic analyses are required to establish an exact recombination rate.

Sequencing of a 0.65kb region in the intron 40 of the vWF gene demonstrated a complex variability. Five STRs named Pol K, F, P1, P2-a and P2-b and an indel polymorphisms (I) are present. We established a routine analysing method to puzzle out the Pol K/F/I/P haplotypes which does not require a sequencing procedure. To recognise the combined polymorphisms as haplotypes, we performed short and middle range PCRs in combination with Nde I and BsmA I restriction tests. Comparison of the amplicon and restriction fragment length reveals the most likely haplotypes of each person involved a kinship test. Furthermore, a SNP allele specific PCR was employed. Additional information can be achieved by typing Pol P2-a and P2-b. Establishing of intron 40 vWF haplotypes using the methods described here can greatly support the resolution of complex kinship cases. This statement is illustrated by demonstration of a family study.

Three tetranucleotide tandem repeats (DXS10079, DXS10074 and DXS10075) which were unutilised so far were evaluated for forensic use. Our investigation was amended to establish a cluster of closely linked markers within a 280-kb region at Xq12. Haplotype stability in 152 meioses was demonstrated in a recombination analysis of 96 three-generation families. Three further known markers, DXS7132, HumARA and DXS981 spanning a region of 3.6 Mb, were also included. No recombination events were detected. Hence, we conclude that this cluster segregates with stable haplotypes, providing a powerful tool in kinship testing.

We investigated 80 patients affected by medium chain AcylCoA dehydrogenase deficiency (MCADD) in a German population, and found the following frequencies of mutation: 985ANG (81.9%); 157CNT (3.1%), 799GNA (3.1%), 244-245 insT (3.1%), 362CNT (1.3%) as well as five rare mutations at frequencies below 0.6%. About 4.4% of the mutations in our patients remained unidentified. After having carried out a mutation typing procedure, we created rapid tests based on a PCR/electrophoresis technology and investigated the four most frequent mutations. Using these screening tests we identified one MCADD case among 409 SIDS victims. These investigations indicate that, in very few cases, MCADD may contribute to SIDS. D 2005 Published by Elsevier B.V.

We present examples of our routine work, which demonstrate the impact of additional ChrX marker typing in special paternity case situations. In each of the seven cases, an extensive testing of autosomal markers failed to yield satisfying results (W >99.9% or 3 exclusions). However, by expanding the analysis to ChrX markers, these criterions were met in five of seven cases. D 2003 Elsevier B.V. All rights reserved.

We investigated the allele distribution of several X-chromosomal (ChrX) markers in population samples from Peru, Ireland, Germany and Ethiopia. We found no homogeneity between the populations. This could be confirmed by v 2 -test. The most impressive differences were seen between the Peruvian and European population samples. D 2003 Elsevier B.V. All rights reserved.

This paper presents sequence and population genetic data of two new X-linked microsatellite markers, suitable for forensic purposes. Data were obtained from a sample of unrelated German individuals (male and female). Two highly informative markers could be added to the panel of ChrX STRs [J. Edelmann, S. Hering, M. Michael, R. Lessig, D. Deichsel, G. Meier-Sundhausen, L. Roewer, I. Plate, R. Szibor, 16 X-chromosome STR loci frequency data from a German population, For. Sci. Int. 124 (2001) 215-218; J. Edelmann, D. Deichsel, S. Hering, I. Plate, R. Szibor, Sequence variation and allele nomenclature for the X-linked STRs DXS9895, DXS8378, DXS7132, DXS6800, DXS7133, GATA172D05, DXS7423 and DXS8377, For. Sci. Int. 129 (2002) 99-103].

Fortschritte auf dem Gebiet der medikamentosen Therapie hangen wesentlich vom Ergebnis klinischer Studien ab. Bei unzureichender Einhaltung des Versuchsdesigns oder unkorrekter Probensammlung ist die Zuverlassigkeit der Studie beeintrachtigt. Eine Verlaufsstudie zeigte unerklarbare Messwerte mit dem Verdacht der Probenmanipulation. Es wurden 10 Paare angeblich identischer Serumproben mit Serumsystemen und DNA-Markern auf ihre Identitat hin untersucht. Keines der Probenpaare zeigte eine vollstandige Ubereinstimmung der Phanotypen. Bei theoretisch mindestens 80 erwarteten Ubereinstimmungen der Phanotypen konnten solche tatsachlich nur 17-mal in den untersuchten Serumsystemen bzw. 9-mal bei den DNA-Markern festgestellt werden. Es zeigten sich 40-mal 3 oder mehr Allele pro Phanotyp; 6-mal wechselte das Geschlecht. Diese Befunde lassen eine betrugerische Absicht annehmen. Der Fall ist Anlass daruber nachzudenken, ob bei bedeutenden klinischen Studien nicht grundsatzlich eine stichprobenartige Uberprufung hinsichtlich der Zuordnung des Probenmaterials als Qualitatsstandard eingefuhrt werden sollte.

A large number of short tandem repeat (STR) markers spanning the entire human X chromosome have been described and established for use in forensic genetic testing. Due to their particular mode of inheritance, X-STRs often allow easy and informative haplotyping in kinship analyses. Moreover, some X-STRs are known to be tightly linked so that, in combination, they constitute even more complex genetic markers than each STR taken individually. As a consequence, X-STRs have proven particularly powerful in solving complex cases of disputed blood relatedness. However, valid quantification of the evidence provided by X-STR genotypes in the form of likelihood ratios requires that the recombination rates between markers are exactly known. In a collaborative family study, we used X-STR genotype data from 401 two- and three-generation families to derive valid estimates of the recombination rates between 12 forensic markers widely used in forensic testing, namely DXS10148, DXS10135, DXS8378 (together constituting linkage group I), DXS7132, DXS10079, DXS10074 (linkage group II), DXS10103, HPRTB, DXS10101 (linkage group III), DXS10146, DXS10134 and DXS7423 (linkage group IV). Our study is the first to simultaneously allow for mutation and recombination in the underlying likelihood calculations, thereby obviating the bias-prone practice of excluding ambiguous transmission events from further consideration. The statistical analysis confirms that linkage groups I and II are transmitted independently from one another whereas linkage groups II, III and IV are characterised by inter-group recombination fractions that are notably smaller than 50%. Evidence was also found for recombination within all four linkage groups, with recombination fraction estimates ranging as high as 2% in the case of DXS10146 and DXS10134.

From 2008 to the end of 2009 the Joint Poison Information Center (PIC) in Erfurt observed 7 incidents involving 17 persons (1 fatality) with signs of carbon monoxide poisoning from indoor barbecues (COFIB). To find out whether COFIB is a regional or a general phenomenon in Germany, Austria and Switzerland, all information about COFIBs recorded by the 11 German-speaking Poison Information Centers and the BfR Berlin were retrospectively analyzed for the period 2000 to 2009. In all, 60 COFIBs (accidental: 90.0 %, suicidal: 8.3%, reason unknown: 1.7%) involving 146 individuals were reported. The number of incidents increased from one case with 2 persons in 2000 to 18 cases involving 34 persons in 2009. The 146 victims (female 26.7%, male 27.4%, gender unknown 45.9%; adults 58.2%, children 24.7%, age unknown 17.1%) lived in 15 of the 16 federal states of Germany and in Switzerland. The highest number of victims was found in Bavaria (23), Brandenburg (18), and Baden-Wuerttemberg (18). The symptoms according to the Poisoning Severity Score were none to mild in 60.3%, moderate in 13.7%, severe in 11.6%, fatal in 6.9% and unratable in 7.5%. No clear correlation was found between the carboxyhemoglobin concentration and the severity of the symptoms. As a rising number of COFIBs often involving several individuals was observed from 2000 to 2009, the general public was informed about the risks of indoor barbecues.

A representative multicenter cystic fibrosis (CF) mutation analysis on about half of all known cystic fibrosis patients of the 5 East German Länder is reported. Analyses for 17 mutations, among them Delta F508, R553X, G542X, S549R,N,I, G551D, S1255X, R347P,H, and Y122X, were performed. As expected, the delta F508 mutation in exon 10 of the CFTR gene is the major gene alteration causing CF in our patients. However, in comparison to studies from Western Germany, a significantly lower percentage of just over 60% is found in our patients, resembling data obtained from slavonic populations. The severe phenotype of cystic fibrosis is most frequently associated with homozygosity for the delta F508 mutation. No particular allele association could be found with the intermediate and mild phenotypes of this disease. The next most frequent of the investigated mutations is R553X (13.3% of non-delta F chromosomes) followed by R347P (9.2%) and G542X (4.4%).

STR DYS19 seems to be one of the most useful markers for population genetic, evolutionary, and forensic applications. However, the authors have noticed that the amplification of the DYS19 polymorphism fails when highly degraded DNA is used as a template. The authors designed a new pair of primers that reduce the DYS19 fragment sizes compared with those of the known protocol. Using these primers, an improved success rate can be achieved, particularly when putrefied samples are under investigation.

This paper presents sequence and population genetic data of the HumDXS6807 short tandem repeat (also known as CHLC.GATA52B03) which is a tetranucleotide repeat polymorphism representing seven alleles of 251-275 bp in length. HumDXS6807 is located at Xpter-Xp22.2, i.e., at a genetic distance of more than 87 and 151 cM from the well-known markers HumARA and HumHPRTB, respectively. Kinship tests in 157 family trios revealed a typical X-linked codominant inheritance; mutations were not found. Population genetic data were obtained by analyzing a Caucasian population sample comprising 308 females and 209 males: polymorphism information content (PIC) = 0.640; Heterozygosity (Het) = 0.668; Mean exclusion chance (MEC) = 0.414. The HumDXS6807 allele distribution met the Hardy-Weinberg expectations.

Experience gained in clinical genetics led to the fundamental idea of using X-chromosomal markers in a wide range of forensic applications. To date more than 30 STRs have been established as forensic markers. Joint typing of very tightly linked STRs yields stable haplotypes, and can be used for establishing the relationship between distant relatives, such as aunt–niece pairs and cousins. For such applications the new ChrX typing kit Argus X-8 ® which is commercially available now is a powerful tool. This paper is aimed at presenting a brief survey of historical developments and discussing present and future aspects of forensic X-chomosomal testing.

We propose that clusters of closely linked markers, which segregate as stable haplotypes, provide a high potential to solve complex kinship cases. It is known that the X-chromosomal centromere region shows an extremely low degree of recombination. Hence, we focused our interest on the region between 56 and 64 Mb distant from the Xp telomere and considered 6 STRs which are now registered in the Genome Data Base as DXS10161, DXS10159, DXS10162, DXS10163, DXS10164, and DXS10165. All of these markers show a tetranucleotide or pentanucleotide structure and exhibit high or medium polymorphic information content. As a peculiarity, DXS10163 is a combination of a pentanucleotide STR and an 18 bp INDEL polymorphism. We report here the primer sequences, the repeat structures, the allele distributions and parameters of forensic interest for a German population sample.

The evaluation of four pairs of X-chromosomal short tandem repeats (STRs), i.e. DXS10135-DXS8378, DXS7132-DXS10074, HPRTB-DXS10101 and DXS7423-DXS10134 was carried out using the Argus X-8 Multiplex amplification kit. These eight STRs are distributed as four closely linked pairs over the entire X-chromosome (ChrX), and for practical reasons they are assigned to four linkage groups 1-4. The genetic distance within the STR pairs is assumed to be

The molecular origin of DNA mutations and the mutation rates were analyzed at 14 short tandem repeat (STR) loci with samples from trio cases derived from 10 different German population samples. STR loci comprised of D2S1360, D3S1744, D4S2366, D5S2500, D6S474, D7S1517, D8S1132, D10S2325, D12S391, D18S51, D19S246, D20S480, D21S226, and D22S689. In a total of 488 meioses, 16 isolated genetic inconsistencies in 8 different STRs were observed, whereas no mutations were found at the other loci. The data of five mutations suggested the presence of silent or null alleles due to sequence variation in primer binding site. This could be confirmed for four suspected cases by the use of alternative primer sets and by DNA sequence analyses. Furthermore, this study revealed nine new allelic variants at five different loci.

Intron 40 of the von Willebrand factor (vWF) gene exhibits a highly variable region of about 0.65 kb, which contains 5 juxtaposed STRs. We sequenced 0.65 kb amplicons from 68 chromosomes and found 2 frequent indel polymorphisms and 5 SNPs. The 68 chromosomes investigated here presented a total of 47 different haplotypes. Regarding the SNP allele distribution in our sample, we arranged our results of the vWF intron 40 into a system of 3 haplotypes, i.e. haplotypes a, b and c. Our review may be valuable in further optimising vWF typing in forensic applications and in avoiding pitfalls. Further attempts to develop sophisticated techniques may soon enable haplotyping using autosomale STR clusters.

At the forensic autopsy of a sexual murder victim, some trace hairs, possibly belonging to the perpetrator, were saved. Initially, the analysis of a pubic hair shaft only revealed the presence of the mitochondrial (mt) DNA haplotype profile consisting of the (CA)(6) allele and the complete hypervariable region 1 (HV1) and 2 (HV2) sequence. Later, typing of some further telogene trace hairs, which had been stored for several years, yielded a nuclear short tandem repeat (STR) profile. We used both the mtDNA haplotype and the STR profile to start a DNA mass screening project involving 2,335 male citizens of the relevant communities. MtDNA screening was carried out by using the CA repeat amplification in combination with an SNP typing procedure based on the restriction site analysis of amplified d-loop sequences. The aim of our paper is to put mass screening with mtDNA up for discussion.

Sequence analysis of the human mitochondrial genome (mtDNA) has proven to be a valuable tool in forensic identity testing and the analysis of crime scene stains. In contrast to the very expensive sequencing technique, typing of different length variants can greatly facilitate screening of a large number of traces for their relevance during casework. Within the mitochondrial control region, a dinucleotide (CA) n repeat locus is present. To assess the discrimination power of this marker, we have determined (CA) n allele distribution and the frequency of heteroplasmy in a population sample of 2,458 Germans. The inclination to develop heteroplasmic mixtures (CA) n /(CA) n−1 was positively correlated with the number of CA repeats in the mtDNA. In addition, we have studied the inheritance patterns of (CA) n repeat sequence heteroplasmy in two pedigrees. In one pedigree, we also found a length heteroplasmy in the homopolymeric C-tract (nt 303–309). Our data show stable inheritance of heteroplasmy within the homopolymeric C-stretch, but rather unstable inheritance regarding the (CA) n repeat locus.

We would like to announce the opening of a new Web site ( http://www.chrx-str.org ), which contains a database surveying current research on chromosome X markers used for forensic purposes, evolutionary anthropology and other genetic research. Currently, we summarise short tandem repeat data with regard to the physical and genetic localisation, repeat structure, allele nomenclature, mutation rates and population genetics. In the future, we may include diallelic markers. The results contained in this database come from published journal articles. The authors of published articles are invited to complement their own papers by submitting data obtained from follow-up studies here. Furthermore, population data which are not able to find space in journals may be published at this Web site. The growing field of ChrX haplotyping is producing an extensive amount of data, which requires a place that can complement journal publications.

This paper presents sequence and population genetic data of the X-linked microsatellite marker DXS6801 (GDB:G00-365-276) which is a tetranucleotide repeat polymorphism representing eight alleles 109-141 bp in length. Data were obtained from a sample of 1146 unrelated German individuals. DXS6801 is located 99.7 cM from Xptel, nearby DXS6809 [Int. J. Legal Med. 117 (2003) 241] and DXS6789 [Forensic Sci. Int. 119 (2001) 42] in Xq21. The new marker could be added to the panel of ChrX STRs, especially usable as a part of the Xq21 linkage group.

The hypervariable tetranucleotide STR polymorphism DXS10011 is a powerful marker for forensic purposes. Investigation of this STR led to an allele nomenclature which is in consensus with the ISFG recommendations. DXS10011 is located at Xq28 and genetically closely linked to DXS7423 and DXS8377 but is unlinked to HPRTB and more distant X-chromosomal STRs. DXS10011 is a very complex marker exhibiting some structural variants within alleles of identical length. Two types of repeat structure (regular and inter-alleles) are known and described as types A and B. Two SNPs which are in strong linkage disequilibrium to the different sequence types were found in the repeat flanking region. The type A sequence consists of a long stretch of uninterrupted homogenous repeats which is highly susceptible to slippage mutation during male meiosis.

The p53 tumor suppressor gene is altered in human cancer. A common polymorphism occurs at codon 72 of exon 4, with two alleles encoding either arginine (CGC) or proline (CCC). No data exist about the association of a distinct codon 72 variant with the histological subtypes of thyroid carcinoma. We developed a new one-step real-time PCR assay on the LightCycler to detect codon 72 polymorphism in the p53 gene. We studied 21 papillary, 18 follicular and 22 anaplastic thyroid carcinomas and compared them with 15 adenomas and 36 normal thyroid tissues (controls); moreover, we compared the cases for histological, clinical and demographic variables and genotype prevalence. In controls, the frequency of the three genotypes Arg/Arg, Arg/Pro, and Pro/Pro was 41.7, 50.0 and 8.3%, respectively. The homozygous proline was not found in benign thyroid adenomas and differentiated thyroid carcinomas. In contrast, all undifferentiated thyroid carcinomas (100%) had the homozygous proline phenotype. The frequency of the two other genotypes Arg/Arg and Arg/Pro was 66.7% and 33.3% in adenomas, 81.0% and 19.0% in papillary thyroid carcinomas, and 83.3% and 16.7% in follicular thyroid carcinomas, respectively. Comparing the genotypes with tumor stage, no correlation was found. However, lymph node and distant metastases status showed a statistically significant prevalence for the homozygous phenotypes Arg/Arg and Pro/Pro. There was no association between a special genotype and age and sex. We conclude that homozygous proline is a potential risk factor favoring the development of an undifferentiated thyroid carcinoma, and that the homozygous phenotypes at codon 72 of p53 are associated with a poorer prognosis of thyroid carcinoma.