Biomedical subjects
Publications and source records attributed to R Szibor.
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.
This paper presents sequence and population genetic data of the X-linked DXS6789 short tandem repeat (STR). The tetranucleotide repeat polymorphism DXS6789, also known as CHLC.GATA31F01, is located at the Xq22.3 region. This locus is unlinked with DXS6807 and slightly linked with ARA, DXS9898 and HPRTB. In kinship testing, DXS6789 is suitable for concomitant use with DXS6807. Population genetic data were obtained by analysing 250 unrelated males and 315 females from East Germany. In this population, the STR exhibited 12 clearly distinguishable alleles ranging from 154 to 198bps in length. DXS6789 is characterised by the following data: polymorphic information content (PIC)=0.70; observed heterozygosity (Het)=0.78; mean exclusion chance (MEC)=0.70. A deviation from the Hardy-Weinberg equilibrium could not be detected. The investigations we performed in 243 mother-child and 161 father-child meioses did not reveal any mutations.
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.
This paper presents sequence and population genetic data for the microsatellite marker DXS101 which is a highly polymorphic X-linked trinucleotide polymorphism with 18 alleles 179-233 bp in length. A polymorphism information content (PIC) of 0.884 and a mean exclusion chance (MEC) of 0.879 were obtained by analysing a Caucasian population sample. A deviation from the Hardy-Weinberg equilibrium (HWE) could not be detected. Kinship tests revealed a typical X-linked inheritance and no mutations were found in 340 meioses. DXS101 is located 104.9-121 cM from the Xp-telomere (Xp-tel) corresponding to Xq21.33-Xq22.3. Concomitant testing of DXS101 and DXS6807 is possible as these two markers are unlinked. The data presented qualify this X-linked microsatellite marker as a useful tool for forensic purposes.
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.
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 report contains the results of two population studies on the X chromosome STR HumHPRTB carried out in a Northern and a Southern region of Germany. The numbers of unrelated individuals were 443 and 335, respectively. Eight alleles (alleles 9 to 16) were found. In female individuals 29 different genotypes were encountered. In German populations the HumHPRTB STR was characterized by the following data: PIC = 0.750; HET = 0.769: MEC = 0.556. Allele distribution met the Hardy-Weinberg expectations. The Northern and Southern populations did not show any significant differences.
HumDXS9898 also known as CHLC x GATA 126G01 is a tetrameric microsatellite marker located at the Xq21.33 pericentromeric region. In kinship testing HumDXS9898 is suitable for concomitant use with HumHPRTB and HumDXS6807 which are separated from HumDXS9898 by genetic map distance of 150 and 80 cM, respectively. HumDXS9898 is closely linked to HumARA. In the German population, HumDXS9898 exhibits seven clearly distinguishable alleles ranging from 189 to 214 basepairs in size. Deviation from Hardy-Weinberg equilibrium could not be detected. The observed heterozygosity was 0.75 for females and the mean exclusion probability was 0.73 for female children. Mutations were not found in the present material.
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.
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To evaluate the significance of microsatellite instability (MI) and loss of heterozygosity (LOH) in the development of different histological subgroups of liposarcomas, we examined 28 tissue-samples from 21 patients and the corresponding non-neoplastic reference tissues. We investigated nine microsatellite loci and detected no MI. LOH for at least one marker was observed in 11 of 28 tumours (39%). Widespread allelic losses were a common characteristic of pleomorphic liposarcomas. Well-differentiated variants did not show LOH (p<0.003). Our findings support the idea that liposarcoma subgroups are defined by different spectra of genetic alterations. Inefficient DNA mismatch repair does not seem to be involved in the oncogenesis of liposarcomas.
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This report gives the results of two population studies on HumD3S1358 from a northern and a southern region of Germany. The numbers of unrelated individuals were 326 and 666, respectively and seven main alleles, three rare allelic variants and 29 different genotypes were encountered. No significant statistical differences were seen between the northern and southern populations. The HumD3S1358 allele distributions were in agreement with Hardy-Weinberg expectations and two mutations were found in 780 meiotic events.
The ratio of mtDNA and a nuclear reference gene was estimated by Southern blotting in the skeletal muscle DNA of a 3-year-old girl who suffered from congenital brain damage, focal epilepsy, hepatomegaly, malabsorption syndrome and severe myopathy. The signal ratio of mtDNA versus 18S rDNA was 22% of the mean value obtained from controls. No major deletions or insertions were found and the MERRF, MELAS and NARP mutations were ruled out. Mitochondrial DNA-encoded enzyme activities and mitochondrial respiration were reduced. The analysis of the NAD(P)H and flavoprotein redox states of intact fibres revealed the presence of mitochondrial dysfunction. In tissue sections a moderate elevation of type I and type II fibre diameter variation was detected, aberrant NADH- and succinate dehydrogenase staining and some ragged red fibres. This suggested that a mitochondrial disorder caused by a decrease in the amount of intact wild-type mtDNA was responsible for the severe myopathy.
We report a dinucleotide repeat polymorphism in the 3' area of the mitochondrial control region. The fragments obtained using a new primer set could be reliably separated by polyacrylamide gel electrophoresis (PAGE) using nondenaturing gels. A total of five alleles [(CA)3 to (CA)7] were detected on silver-stained gels. The 90 bp product corresponds to allele 5. Samples from one African and three European populations were characterized. Significant differences could be demonstrated as to the incidence of single alleles and allele distributions in different populations. These differences were found between the three European and one African Bantu population. For specific forensic questions the mitochondrial CA repeat is well suited. Gene diversities in populations of Germany, Hungary, the Russian Federation and Cameroon were 0.36, 0.40, 0.34, 0.52, respectively.