Publications by authors named "Jeanett Edelmann"

35 Publications

German population data for 18 X-STRs: a hexaplex PCR adding two clusters of X-STRs to the Argus X-12 set and expanding the German haplotype databases.

Int J Legal Med 2020 Nov 4;134(6):2061-2062. Epub 2020 May 4.

Institute of Legal Medicine, University of Leipzig, Leipzig, Germany.

In kinship analysis, large data sets with estimated haplotype frequencies for marker clusters are very important for the likelihood calculation. Practical use of the X-STRs demonstrated that in some complex kinship cases, the marker set of the Investigator Argus X-12 kit can be insufficient. This study aimed to extend the German data base of the Argus X-12 kit (1037 haplotypes) and for a cluster in Xq21 (806 haplotypes) with additional 700 male haplotypes and to include a further cluster in Xp22.3 to complete the X-STR marker set for complex kinship cases.
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http://dx.doi.org/10.1007/s00414-020-02306-zDOI Listing
November 2020

X-chromosomal 21-indel marker panel in German and Baltic populations.

Int J Legal Med 2016 Mar 12;130(2):357-60. Epub 2015 Jul 12.

Institute of Legal Medicine, University of Leipzig, Leipzig, Germany.

In order to verify specific biallelic X-indels and their characteristic properties in distinct populations, one German and three Baltic population groups (Estonia, Latvia, and Lithuania) have been analyzed by a short amplicon method, which also enables detection of degraded DNA samples. To combine 21 indels in a single multiplex PCR, all products were arranged according to their expected amplicon length (~40-160 bp) on the basis of three different fluorochromes. Separation of PCR products was carried out in a single capillary electrophoresis. Data evaluating was performed including five further indel markers which have already been tested in identical samples, resulting in altogether 26 markers. The majority of the genetic material showed combinations of insertion elements (L-fragments). Combinations of deletion elements (S-fragments) in contrast occurred with significant lower ratios. Hardy-Weinberg equilibrium (HWE) was observed for all markers except for MID1361 and MID329. This was attributed to an insufficient number of samples. For two known linkage groups within the 26-indel set (MID357-MID356 and MID3690-MID3719-MID2089), haplotype data were determined. A pairwise comparison of German and Baltic allele frequencies did not show significant deviation. This result indicates a possible genetic association between all four population groups. The calculated biostatistical parameters show high forensic efficiency for this set of indel markers. In a segregation analysis investigating 194 meiosis, no mutations have been detected regarding expected transmission patterns.
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http://dx.doi.org/10.1007/s00414-015-1221-3DOI Listing
March 2016

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

Forensic Sci Int Genet 2014 Sep 28;12:12-23. Epub 2014 Apr 28.

Forensische Genetik, Kantonsspital Aarau AG, Switzerland.

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.
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http://dx.doi.org/10.1016/j.fsigen.2014.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4127773PMC
September 2014

Collaborative genetic mapping of 12 forensic short tandem repeat (STR) loci on the human X chromosome.

Forensic Sci Int Genet 2012 Dec 27;6(6):778-84. Epub 2012 Mar 27.

Institut für Medizinische Informatik und Statistik, Christian-Albrechts-Universität Kiel, Brunswiker Straße 10, 24105 Kiel, Germany.

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.
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http://dx.doi.org/10.1016/j.fsigen.2012.02.015DOI Listing
December 2012

Long QT syndrome mutation detection by SNaPshot technique.

Int J Legal Med 2012 Nov 18;126(6):969-73. Epub 2011 Jul 18.

Institute of Forensic Medicine, University of Leipzig, Leipzig, Germany.

Long QT syndrome (LQTS) is a cardiac disorder with an abnormality of cardiac rhythm associated with sudden death especially in younger, apparently healthy individuals. If there is no clear cause of death detectable during comprehensive coroner's inquest (autopsy-negative cases), you have to consider LQTS and other heritable arrhythmia syndromes. A molecular genetic screening regarding mutations in associated genes can help to ensure the cause of death and to protect affected family members. Genetic testing of LQTS, currently performed mainly by sequencing, is still very expensive and time consuming. With this study we present a rapid and reasonable method for the simultaneously screening of some of the most common mutations associated with LQTS, focused on the KCNQ1 and KCNH2 genes. With the method of SNaPshot minisequencing, a total of 58 mutations were analyzed in four multiplex assays which were successfully established and optimized. The comparison with samples previously analyzed by direct sequencing showed concordance. Furthermore, autopsy-negative cases were tested but no mutations could be observed in any of the specimen. The presented method is well suitable for LQTS mutation screening. An enhancement to further mutations and population-based investigations regarding mutation frequencies should be the aim of prospective studies.
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http://dx.doi.org/10.1007/s00414-011-0598-xDOI Listing
November 2012

X chromosomal recombination--a family study analysing 39 STR markers in German three-generation pedigrees.

Int J Legal Med 2010 Sep 20;124(5):483-91. Epub 2009 Nov 20.

Institut für Rechtsmedizin, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.

Typing of polymorphisms on the human chromosome X (ChrX) has become a standard technique in forensic genetics, and a growing number of short tandem repeats (STRs) has been established. Knowledge of marker recombination is of great significance especially when ChrX typing is used in forensic kinship testing. It is known that meiotic recombination is not a simple function of physical distance but crossing over events tend to be clustered. Information on genetic distances between markers can be gathered by family studies and by interpolation of gene bank data such as the Rutgers map. We typed DNA samples of pedigrees consisting of mothers with several sons and grandfather-mother-son constellations and report here the recombination characteristics of 39 ChrX STRs in up to 135 meioses.
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http://dx.doi.org/10.1007/s00414-009-0387-yDOI Listing
September 2010

The Y-chromosomal STRs DYS481, DYS570, DYS576 and DYS643.

Leg Med (Tokyo) 2009 Apr 28;11 Suppl 1:S109-10. Epub 2009 Feb 28.

Institute of Legal Medicine, University of Leipzig, Johannisallee 28, 04103 Leipzig, Germany.

The Y-STRs DYS481, DYS570, DYS576, and DYS643 were investigated in a West Saxonian population sample, which have been previously typed with the well known minimal or extended haplotype of Y-STRs. Observed allele frequencies are reported along with the allele nomenclature based on sequencing. Gene diversities as well as the haplotype diversity of the four markers--DYS481, DYS570, DYS576 and DYS643--were calculated and compared with published data of other population samples. The discrimination capacities of the markers show a high potential for forensic purposes.
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http://dx.doi.org/10.1016/j.legalmed.2009.01.063DOI Listing
April 2009

Validation of six closely linked STRs located in the chromosome X centromere region.

Int J Legal Med 2010 Jan 20;124(1):83-7. Epub 2009 Feb 20.

Institut für Rechtsmedizin, Universität Leipzig, Leipzig, Germany.

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.
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http://dx.doi.org/10.1007/s00414-009-0328-9DOI Listing
January 2010

Population genetic evaluation of eight X-chromosomal short tandem repeat loci using Mentype Argus X-8 PCR amplification kit.

Forensic Sci Int Genet 2008 Jan 29;2(1):69-74. Epub 2007 Sep 29.

Biotype AG, Moritzburger Weg 67, 01109 Dresden, Germany.

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 <1cM, whereas the pair to pair space is about 50 cM or more. Here, we present single STR allele frequencies, haplotype frequencies of the respective STR pairs and further population genetic parameters of forensic interest. Most data refer to a German population, however small samples from Ghana and Japan were also investigated. Furthermore, sequencing of all STR loci displayed the presence of microvariant alleles and variations in the repeat flanking region. A total of 350 meioses investigated here revealed only one sperm DXS7132 mutation. For analysis of linkages within the STR pairs a study involving 104 female meiosis with respect to recombination events was performed. The STR panel presented here provides a powerful tool for solving complex kinship in the case that X-chromosomal lineages can be taken under investigation.
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http://dx.doi.org/10.1016/j.fsigen.2007.08.013DOI Listing
January 2008

Characterisation of the STR markers DXS10146, DXS10134 and DXS10147 located within a 79.1 kb region at Xq28.

Forensic Sci Int Genet 2008 Jan 27;2(1):41-6. Epub 2007 Sep 27.

Institute of Legal Medicine, University Leipzig, Leipzig, Germany.

Three polymorphic X-chromosomal STR markers within a 79 kb region at Xq28 were studied and registered in the GDB as DXS10146, DXS10134 and DXS10147. These markers were molecular characterised and evaluated for their forensic usage. As a result DXS10134 was recently integrated in the commercial available test kit Mentype Argus X-8. At locus DXS10146 we found 23 alleles with PIC and HET values of 0.878 and 0.887. Locus DXS10134 showed 17 alleles with PIC and HET values of 0.844 and 0.858. At locus DXS10147 only 5 alleles with some lower PIC and HET values of 0.636 and 0.692 were found. Additionally, the already known and closely linked STR DXS7423 was included into the haplotyping and recombination studies. Testing this cluster a German population of 404 males revealed the presence of 311 haplotypes. Recombination analysis was performed in 109 father-daughter-grandson trios in which two crossing over events were observed located in the 65.8 kb region between DXS10146 and DXS10134. By using this STR complex for haplotyping in kinship testing further genetic analyses are required to establish an exact recombination rate.
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http://dx.doi.org/10.1016/j.fsigen.2007.08.001DOI Listing
January 2008

New alleles and mutational events at 14 STR loci from different German populations.

Forensic Sci Int Genet 2007 Dec 31;1(3-4):232-7. Epub 2007 May 31.

Biotype AG, Moritzburger Weg 67 D, 01109 Dresden, Germany.

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.
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http://dx.doi.org/10.1016/j.fsigen.2007.04.001DOI Listing
December 2007

The STR cluster DXS10148-DXS8378-DXS10135 provides a powerful tool for X-chromosomal haplotyping at Xp22.

Int J Legal Med 2008 Nov 8;122(6):489-92. Epub 2008 Aug 8.

Institut für Rechtsmedizin, Otto-von-Guericke-Universität Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany.

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.
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http://dx.doi.org/10.1007/s00414-008-0277-8DOI Listing
November 2008

Spontaneous remission of acute myeloid leukemia relapse after hematopoietic cell transplantation in a high-risk patient with 11q23/MLL abnormality.

Acta Haematol 2008 27;119(2):111-4. Epub 2008 Mar 27.

Department of Hematology, Oncology and Coagulation, University of Leipzig, Leipzig, Germany.

A 35-year-old female patient was diagnosed with acute myeloid leukemia with multiple genetic aberrations [48 XX, del(3)(q21), +6, t(11;15)(q23;q15), +21] including an 11q23/MLL abnormality. The patient achieved a complete remission after one induction chemotherapy cycle. After three courses of consolidation, a matched unrelated hematopoietic cell transplantation (HCT) was performed. Following an upper respiratory tract infection 7 years after transplant, her blood counts declined to leukocytes of 1 x 10(9)/l, platelets of 51 x 10(9)/l and hemoglobin of 7.5 g/dl. A bone marrow aspirate revealed 55% leukemic blasts carrying the unfavorable genetic aberrations seen at initial diagnosis (11q23/MLL). In the absence of any disease-specific treatment, the leukemic blasts cleared from the bone marrow within 6 days after diagnosis of relapse and peripheral blood counts returned to normal. Molecular analysis of the 11q23/MLL rearrangement was used to evaluate minimal residual disease, which became undetectable in repetitive FISH analyses. This is the first report of spontaneous remission in a patient with initially a multiaberrant leukemic cell clone and a proven 11q23/MLL abnormality at relapse after HCT.
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http://dx.doi.org/10.1159/000121827DOI Listing
June 2008

Adenoid squamous carcinoma (pseudoangiosarcomatous carcinoma) of the vulva: a rare but highly aggressive variant of squamous cell carcinoma-report of a case and review of the literature.

Int J Gynecol Pathol 2008 Apr;27(2):288-91

Institute of Pathology, Division of Gynecologic Pathology, Leipzig University, Leipzig, Germany.

Pseudoangiosarcomatous squamous cell carcinoma is an unusual but aggressive variant of acantholytic squamous cell carcinoma of the vulva that mimics angiosarcoma on histology. We present a case of a 57-year-old woman with bilateral inguinal metastatic disease at the time of diagnosis, who died 4 months later because of distant metastatic disease to the lungs. Molecular analysis did not reveal any human papillomavirus infection. Because of the positive p53 immunostaining and the association to lichen sclerosus and simple type of high-grade vulvar intraepithelial neoplasia, alteration of p53 tumor suppressor gene might be involved in the pathogenesis of vulvar pseudoangiosarcomatous squamous cell carcinoma. However, further molecular studies are required.
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http://dx.doi.org/10.1097/PGP.0b013e3181569904DOI Listing
April 2008

Fate of extrahepatic human stem and precursor cells after transplantation into mouse livers.

Hepatology 2007 Sep;46(3):861-70

Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany.

Unlabelled: In recent years, a large number of groups studied the fate of human stem cells in livers of immunodeficient animals. However, the interpretation of the results is quite controversial. We transplanted 4 different types of human extrahepatic precursor cells (derived from cord blood, monocytes, bone marrow, and pancreas) into livers of nonobese diabetic/severe combined immunodeficiency mice. Human hepatocytes were used as positive controls. Tracking of the transplanted human cells could be achieved by in situ hybridization with alu probes. Cells with alu-positive nuclei stained positive for human albumin and glycogen. Both markers were negative before transplantation. However, cells with alu-positive nuclei did not show a hepatocyte-like morphology and did not express cytochrome P450 3A4, and this suggests that these cells represent a mixed cell type possibly resulting from partial transdifferentiation. Using antibodies specific for human albumin, we also observed a second human albumin-positive cell type that could be clearly distinguished from the previously described cells by its hepatocyte-like morphology. Surprisingly, these cells had a mouse and not a human nucleus which is explained by transdifferentiation of human cells. Although it has not yet been formally proven, we suggest horizontal gene transfer as a likely mechanism, especially because we observed small fragments of human nuclei in mouse cells that originated from deteriorating transplanted cells. Qualitatively similar results were obtained with all 4 human precursor cell types through different routes of administration with and without the induction of liver damage.

Conclusion: We observed evidence not for transdifferentiation but instead for a complex situation including partial differentiation and possibly horizontal gene transfer.
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http://dx.doi.org/10.1002/hep.21745DOI Listing
September 2007

Complex variability of intron 40 of the von Willebrand factor (vWF) gene.

Int J Legal Med 2008 Jan 2;122(1):67-71. Epub 2007 Feb 2.

Institut für Rechtsmedizin, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.

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.
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http://dx.doi.org/10.1007/s00414-006-0149-zDOI Listing
January 2008

Compound heterozygous mutations of the SBDS gene in a patient with Shwachman-Diamond syndrome, type 1 diabetes mellitus and osteoporosis.

Pancreatology 2006 10;6(6):549-54. Epub 2006 Nov 10.

Medizinische Klinik und Poliklinik II, Universitatsklinikum Leipzig, Leipzig, Germany.

Shwachman-Diamond syndrome (SDS) is characterized by exocrine pancreatic insufficiency, skeletal abnormalities and hematological dysfunction. The genetic analysis of the SBDS gene and the long-term follow-up of a 37-year-old man with SDS, osteoporosis and type 1 diabetes are reported. Analysis of the SBDS gene revealed a compound heterozygous genotype with 7 mutations. This genotype is the result of the inheritance of abnormal alleles from both healthy parents. We identified putatively non-functional gene conversions from the SBDS pseudogene into the otherwise normal SBDS gene in each of the parentally inherited alleles. The association of SDS and type 1 diabetes mellitus seems to be coincidental and not associated to distinct mutations of the SBDS gene. Osteoporosis in patients with SDS may be the result of a primary defect of the bone metabolism and not of a nutritional problem, although our patient had chronic hypophosphatemia. The long-term follow-up of this patient provides interesting insights into the course of SDS, showing the complexity of genotype-phenotype correlations and the possible influence of other modifying genes and/or environmental factors that might determine the phenotypic presentation of SDS in an individual patient.
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http://dx.doi.org/10.1159/000096978DOI Listing
April 2007

ErbB-3 predicts survival in ovarian cancer.

J Clin Oncol 2006 Sep 8;24(26):4317-23. Epub 2006 Aug 8.

Department of Gynecology and Obstetrics, University of Mainz, Mainz, Germany.

Background: HER3 (erbB-3) is a member of the epidermal growth factor receptor (EGFR) family. After dimerization with other members of the EGFR family several signal transduction cascades can be activated, including phosphoinosite 3'-kinase (PI3-K)/Akt and extracellular signal-regulated kinase (ERK1/2). Here, we studied a possible association between HER3 expression and prognosis in patients with ovarian cancer.

Methods: Tumor tissue of 116 consecutive patients diagnosed with primary epithelial ovarian cancer between 1986 and 1995 was analyzed immunohistochemically for HER3 expression. A possible influence of HER3 expression on survival was studied by multivariate Cox regression adjusting for established clinical prognostic factors.

Results: A positive HER3 expression was observed in 53.4% of the patients. HER3 expression was associated with decreased survival in proportional hazard modeling, including the International Federation of Gynecology and Obstetrics (FIGO) stage, histologic grade and type, residual disease, and age. After likelihood ratio forward as well as backward selection, only HER3 expression (hazard ratio, 1.71; 95% CI, 1.10 to 2.67; P = .018), FIGO stage (hazard ratio, 4.78; 95% CI, 1.89 to 12.08; P = .001), residual tumor (hazard ratio, 2.69; 95% CI, 1.40 to 5.17; P = .003), and age (hazard ratio, 2.06; 95% CI, 1.17 to 3.65; P = .013) were found to be significant. Kaplan-Meier plots demonstrated a clear influence of HER3 expression on survival time. Median survival time was 3.31 years (95% CI, 1.93 to 4.68) for patients with low HER3 expression, compared with only 1.80 years (95% CI, 0.83 to 2.78) for patients with HER3 overexpression (log-rank test P = .0034).

Conclusion: HER3 may represent a new prognostic factor in primary epithelial ovarian cancer. Pending validation, exploration of therapeutic strategies to block HER3 could be warranted.
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http://dx.doi.org/10.1200/JCO.2005.04.8397DOI Listing
September 2006

p16, p14, p53, and cyclin D1 expression and HPV analysis in small cell carcinomas of the uterine cervix.

Int J Gynecol Pathol 2006 Apr;25(2):182-6

Institute of Pathology, Division of Gynecopathology, and Department of Obstetrics and Gynecology, University of Leipzig, Leipzig, Germany.

Small cell carcinomas (SmCCs) of the uterine cervix are rare tumors. The knowledge regarding protein expression of several checkpoint candidates of cell cycle regulation is limited. Surgically treated SmCCs were selected from our files for immunohistochemical staining (neuroendocrine markers, p53, p16, p14, and cyclin D1). Polymerase chain reaction analysis, using general primers, was performed for human papillomavirus analysis. Nine of 677 tumors (1.3%) were classified as SmCCs after Grimelius staining (8/9 tumors positive) and immunohistochemical reaction against neurone-specific enolase, chromogranin A, synaptophysin (7/9 positive tumors), and CD 56 (8/9 positive tumors). All specimens were positive for at least two of the above. Two SmCCs were p53 positive and one case was p14 positive. Cyclin D1 staining was completely negative. All cases showed strong nuclear and/or cytoplasmic p16-immunostaining. Seven tumors represented human papillomavirus positivity for high-risk types. Four patients died of the tumor after a median time of 36.7 months (range, 15-56 months), representing a 5-year survival rate of 56%. The results suggest that p16 is up-regulated or accumulated in the SmCCs of the uterine cervix, probably caused by infection with human papillomavirus. p14 inactivation is of high prevalence in SmCCs and detection rate of p53 is similar to other histologic types of cervical carcinomas.
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http://dx.doi.org/10.1097/01.pgp.0000185406.85685.dfDOI Listing
April 2006

DXS10079, DXS10074 and DXS10075 are STRs located within a 280-kb region of Xq12 and provide stable haplotypes useful for complex kinship cases.

Int J Legal Med 2006 Nov 13;120(6):337-45. Epub 2005 Dec 13.

Institut für Rechtsmedizin, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.

The evaluation of the short tandem repeat (STR) markers DXS10079, DXS10074 and DXS10075 was amended to establish a STR cluster spanning a genetic distance<1 cM. These three STRs are located within a 280-kb region at Xq12 and provide stable haplotypes useful for solving complex kinship cases. Theoretically, this cluster could give rise to 2,548 different haplotypes in the German population and the genotyping of 781 men revealed the presence of 172 haplotypes. Since the three STRs were shown to be in strong linkage disequilibrium (LD), haplotype frequencies cannot be computed on the basis of a single locus allele frequency alone but have to be estimated directly. Here, we present data on linkage, haplotype frequencies and LD in a German population. Further clusters from other regions of the X chromosome will be published in the future to cover the chromosome with a well-structured network of highly informative sites.
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http://dx.doi.org/10.1007/s00414-005-0061-yDOI Listing
November 2006

A new Web site compiling forensic chromosome X research is now online.

Int J Legal Med 2006 Jul 25;120(4):252-4. Epub 2005 Aug 25.

Institut für Rechtsmedizin, Otto-von-Guericke-Universität Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany.

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.
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http://dx.doi.org/10.1007/s00414-005-0029-yDOI Listing
July 2006

Haplotyping of STR cluster DXS6801-DXS6809-DXS6789 on Xq21 provides a powerful tool for kinship testing.

Int J Legal Med 2005 Nov 11;119(6):363-9. Epub 2005 Aug 11.

Institut für Rechtsmedizin, Otto-von-Guericke-Universität Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany.

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.
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http://dx.doi.org/10.1007/s00414-005-0550-zDOI Listing
November 2005

Population data of Y-chromosomal STRs in Russian males of the Primorye region population.

Forensic Sci Int 2006 May 17;159(1):71-6. Epub 2005 Jun 17.

Institute of Legal Medicine, University of Leipzig, Johannisallee 28, 04103 Leipzig, Germany.

Data of eight Y-chromosomal STRs, the so called "minimal core set", were obtained from 152 unrelated males of the Primorye region of Russia. The allelic frequencies correspond to other European populations. The background is a settlement of males from the European part of Russia, Ukraine and other states which were included in the former western part of the Soviet Union. On the other hand the distribution of the most frequent haplotypes differs to the Ukraine and Russian population. The most frequent haplotype was obtained five times in the population corresponding to 3.3%. The haplotype data reported here have been included into the Y-STR database maintained at the Institute of Legal Medicine, Humboldt-University, Berlin.
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http://dx.doi.org/10.1016/j.forsciint.2005.05.018DOI Listing
May 2006

Significant genetic differentiation between Poland and Germany follows present-day political borders, as revealed by Y-chromosome analysis.

Hum Genet 2005 Sep 16;117(5):428-43. Epub 2005 Jun 16.

Department of Forensic Molecular Biology, Medical-Genetic Cluster, Erasmus University Medical Center Rotterdam, PO Box 1738, 3000, DR Rotterdam, The Netherlands.

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.
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http://dx.doi.org/10.1007/s00439-005-1333-9DOI Listing
September 2005

Validation of the X-linked STR DXS6801.

Forensic Sci Int 2005 Mar;148(2-3):219-20

Institut für Rechtsmedizin, Universität Leipzig, Johannisallee 28, Leipzig 04103, Germany.

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.
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http://dx.doi.org/10.1016/j.forsciint.2004.04.069DOI Listing
March 2005

DXS10011: studies on structure, allele distribution in three populations and genetic linkage to further q-telomeric chromosome X markers.

Int J Legal Med 2004 Dec 10;118(6):313-9. Epub 2004 Jul 10.

Institut für Rechtsmedizin, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.

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.
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http://dx.doi.org/10.1007/s00414-004-0467-yDOI Listing
December 2004
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