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Bernd Brinkmann

Publications and source records attributed to Bernd Brinkmann.

At least 19 recordsLinked to original sources
PubMed2006

Y-chromosomal microsatellite mutation rates in a population sample from northwestern Germany.

To estimate Y-chromosomal short tandem repeat (Y-STR) mutation rates, 15 loci (i.e., DYS19, DYS389 I/II, DYS390, and DYS393; DYS437, DYS438, DYS439, and DYS385; DYS391, DYS392, YCA II, and DXYS156) were analyzed in a sample of 1,029 father/son pairs from Westphalia, northwestern Germany. Among 15,435 meiotic allele transfers, 32 mutations were observed; thus, the mutation rate across all 15 Y-STR loci was 2.1 x 10(-3) per locus (95% C.I.: 1.5-3.0 x 10(-3)). With the exception of a three-repeat mutation at DYS385, all remaining mutations were single repeat mutations. Repeat losses were more frequent than gains (20:12), and the mutation rate appeared to increase with age. The Y haplogroups that were detected in the individuals showing a mutation reflect the haplogroup distribution in the Westphalian population. Additionally, the correlation of surnames and haplotypes was tested: Only 49 surnames occurred more than once, and only two men with the same rare surname shared the same haplotype. All other men with identical surnames carried different haplotypes.

Alleles↗
PubMed2006

Y-STR haplotypes in populations from the Eastern Mediterranean region of Turkey.

We present the frequency distributions of Y-haplotypes determined by ten Y-chromosomal STR polymorphisms (i.e., DXYS156-Y, DYS19, DYS385, DYS389 I and II, DYS390, DYS391, DYS392, DYS393) in unrelated males from the Eastern Mediterranean region of Turkey (104 Turkish and Arabian-speaking Eti Turks from Adana area, 111 Roma and 110 Turks, Kahramanmara degrees area). The haplotype diversity was 0.974 in the Eti Turks, 0.979 in the Roma, and 0.989 in the Turks. Two variant alleles were characterized by sequencing, i.e., allele 9.2 at DXYS156 and 12.2 at DYS385. Some of the haplotypes are particular to one of the three populations; some are shared by all three populations. A search against the Y-Haplotype Reference Database revealed several matches to samples not only from Turkey and neighboring regions (e.g., Syria, Iraq) but also from all over Europe.

Alleles↗
PubMed2006

Meiosis study in a population sample from Afghanistan: allele frequencies and mutation rates of 16 STR loci.

The 16 short tandem repeat systems D3S1358, VWA, FGA, TH01, TPOX, CSF1PO, D5S818, D13S317, D7S820, ACTBP2, D2S1338, D16S539, D19S433, D21S11, D18S51 and D8S1179 were amplified in a population sample composed of 333 immigrants from Afghanistan. The 16 loci met Hardy-Weinberg expectations and possess a combined matching probability of 1 in 3.6 x 10(14) and a combined mean exclusion chance greater than 0.9996 in this Afghan population. Approximately 12,000 meiotic transfers were investigated and 19 mutations were observed in the repeat units of FGA (n=6), ACTBP2 (n=5), D3S1358 (n=2), D5S818 (n=2), D7S820 (n=2), VWA (n=1) and D8S1179 (n=1).

Adult↗
PubMed2006

Cardiac arrhythmias and sudden death in infancy: implication for the medicolegal investigation.

Genetically transmitted diseases are an important cause of juvenile sudden cardiac death (SCD). In a considerable proportion of individuals in which a medicolegal investigation is performed, structural heart disease is absent, and the medical examiner fails to discover an adequate cause of death. In such cases, an inherited arrhythmogenic disease should be considered, which manifests with life-threatening ventricular tachycardia or SCD. Molecular diagnosis is progressively becoming an important tool for these questions. Therefore, postmortem genetic testing ("molecular autopsy") should be considered as a part of the comprehensive medicolegal investigation in SCD cases without apparent structural heart disease. It will have implications not only for the deceased individual but also for living family members in preventing (further) cardiac events by expert counseling, appropriate lifestyle adjustment, and adequate treatment, if available.

Arrhythmias, Cardiac↗
PubMed2006

Fatal leaflet escape in an Edwards TEKNA aortic prosthesis.

The case is reported of a 26-year-old male patient who died eight years after the replacement of an aortic valve with a bileaflet mechanical valve (TEKNA; Edwards, USA). Following prosthesis implantation, the patient had been in a good state of health, and his death occurred unexpectedly. Forensic autopsy revealed a leaflet escape, with two fragments of the leaflet being found bilaterally in the common iliac arteries. Death occurred due to an acute cardiac insufficiency. Immunohistochemical investigations revealed fresh myocardial fiber necroses. Stereomicroscopic and scanning electron microscopic investigations demonstrated surface erosions of the leaflet. Although the valve was withdrawn from the market in June 2000, it had previously been implanted in over 18,000 patients. Thus, from a clinical viewpoint, the question of using a prophylactic replacement in affected patients must be discussed.

Adult↗
PubMed2005

Sudden infant death syndrome and long QT syndrome: an epidemiological and genetic study.

Sudden infant death syndrome (SIDS) is a frequent cause of death among infants. The etiology of SIDS is unknown and several theories, including fatal ventricular arrhythmias, have been suggested. We performed an epidemiological and genetic investigation of SIDS victims to estimate the presence of inherited long QT syndrome (LQTS) as a contributor for SIDS. Forty-one consecutively collected and unrelated SIDS cases were characterized by clinical and epidemiological criteria. We performed a comprehensive gene mutation screening with single-strand conformation polymorphism analysis and sequencing techniques of the most relevant LQTS genes to assess mutation frequencies. In vitro characterization of identified mutants was subsequently performed by heterologous expression experiments in Chinese hamster ovary cells and in Xenopus laevis oocytes. A positive family history for LQTS was suspected by mild prolonged Q-T interval in family members in 2 of the 41 SIDS cases (5%). In neither case, a family history of sudden cardiac death was present nor a mutation could be identified after thorough investigation. In another SIDS case, a heterozygous missense mutation (H105L) was identified in the N-terminal region of the KCNQ1 (LQTS 1) gene. Despite absence of this mutation in the general population and a high conservational degree of the residue H105 during evolution, electrophysiological investigations failed to show a significant difference between wild-type and KCNQ1(H105L)/minK-mediated I(Ks) currents. Our data suggest that a molecular diagnosis of SIDS related to LQTS genes is rare and that, even when an ion channel mutation is identified, this should be regarded with caution unless a pathophysiological relationship between SIDS and the electrophysiological characterization of the mutated ion channel has been demonstrated.

Age Distribution↗
PubMed2005

Characterisation of variant alleles in the STR systems D2S1338, D3S1358 and D19S433.

We have observed three hitherto undescribed off-ladder alleles at three widely used STR loci. These were isolated, sequenced and designated as follows: allele 10 (D2S1338, one case), allele 21 (D3S1358, two cases) and allele 6.2 (D19S433, six cases). These sequences are described in comparison to non-variant alleles, and their implications for the semi-automated STR analysis will be discussed.

Alleles↗
PubMed2005

Specific traces in stun gun deployment.

Stun guns are electric shocking devices that can be deployed as defensive or offensive weapons. The aim of this study was the identification of several types of trace evidence for corroborating deployment and providing clues to the weapon actually used. In a series of some 250 tests, the after-effects of firing a stun gun were studied under the differential influence of factors, such as time duration, distance from target, and bare skin vs clothing as target surface. Examination with scanning electron microscopy (SEM) and energy dispersive X-ray spectrometer (EDS) demonstrated the presence of metallic deposits corresponding to the electrodes of the device used. The observed differences in the number of these pellets were related to the length of deployment in seconds and to the distance of the weapon from the target surface. Longer duration of firing was consistently associated with a larger number of metallic deposits. Elemental composition of the latter provided clues to the type of device used and its current status in terms of wear and tear. Further trace evidence we examined included craters on the target surface and their pattern of dissemination on human skin, textiles, and leather. It is concluded that the use of carbon tabs for examination with SEM/EDS offers a practicable method for collecting trace material following stun gun deployment. Important groups of trace evidence do exist, and their collection and examination appear feasible.

Clothing↗
PubMed2005

Real-time quantitative PCR assay for the detection of Helicobacter pylori: no association with sudden infant death syndrome.

Helicobacter pylori infection is known to be one of the most common chronic infectious diseases in humans. Recently, a hypothesis was proposed that H. pylori infection could be a frequent cause for sudden infant death syndrome (SIDS). We have investigated this postulated association by examining formalin-fixed paraffin-embedded gastric tissues of a retrospective cohort of 94 SIDS cases: The presence of H. pylori was inferred from a newly developed real-time quantitative PCR assay with SYBR Green I detection. This assay is based on the amplification of the single-copy H. pylori-specific glmM gene. Accuracy and precision were verified using a plasmid containing a 977-bp fragment of this glmM gene. The assay was very sensitive, and as few as 30 template copies per PCR reaction could be detected even in the presence of excess human DNA. The assay was validated on mucosal biopsy samples of patients with known H. pylori infections. Interfering effects due to SIDS gastric tissue were excluded. Only two (2.1%) of the SIDS samples yielded H. pylori DNA copy numbers and only beyond the lowest standard concentration. These results could be confirmed independently by immunohistochemistry using an H. pylori-specific antibody. Thus, an infection by H. pylori is very rare in cases of SIDS, and thus the postulated association of H. pylori infection and SIDS cannot be confirmed.

Autopsy↗
PubMed2005

Modifiable risk factors for SIDS in Germany: results of GeSID.

BACKGROUND: The incidence of sudden infant death syndrome (SIDS) has been falling in Germany over the last decade. However, little is known about the prevalence and the importance of well-known risk factors in Germany since a local prevention campaign in 1992. DESIGN: A 3-y, population-based, case-control study was conducted in half of Germany, consisting of 333 cases. All sudden and unexpected deaths in infancy, if they fitted the inclusion criteria, were included in the study. Parental interview was carried out soon after the death, and three living control infants, matched for age, gender, region and sleep time, were recruited. RESULTS: The prevalence of placing infants prone to sleep was only 4% in the control group, but this was associated with a markedly increased risk of SIDS (adjusted odds ration, aOR=6.08). Other modifiable risk factors for SIDS were: maternal smoking during pregnancy, breastfeeding for less than 2 wk (aOR=1.71) and co-sleeping (aOR=2.71), while using a pacifier during the last sleep reduced the risk (aOR=0.39). CONCLUSIONS: Previously recognized risk factors for SIDS also occur in Germany. Despite knowledge about the major modifiable risk factors for SIDS, these factors are still present in Germany. To reduce the incidence of SIDS in Germany, a continued effort is needed to inform all parents about preventable risk factors for SIDS.

Adult↗
PubMed2004

Allelic drop-out in the STR system ACTBP2 (SE33) as a result of mutations in the primer binding region.

In the course of routine genotyping of forensic reference samples by multiplex PCR, an allelic drop-out due to mutations in the primer binding regions of the highly polymorphic STR marker ACTBP2 was observed in 17 samples. The variation rate was estimated to be 0.0014 (95% confidence interval: 0.0006-0.003). The most frequently found mutation was an G to A transition in the reverse primer binding region which was present in 14 out of 17 cases. To overcome the problem we have added a modified reverse primer to different multiplex kits that led to the correct genotype.

Binding Sites↗
PubMed2004

The EDNAP mitochondrial DNA population database (EMPOP) collaborative exercises: organisation, results and perspectives.

This paper presents an overview of the organisation and the results of the collaborative exercises (CE) of the European DNA Profiling (EDNAP) Group's mitochondrial DNA population database project (EMPOP). The aim of the collaborative exercises was to determine whether uniformity of mtDNA sequencing results could be achieved among different laboratories. These were asked to sequence either the complete mtDNA control region or the two hypervariable regions HVI (16024-16365) and HVII (73-340) from DNA extracts, buccal swabs or bloodstains, proceeding in accordance with the protocol and strategies used in each individual laboratory. The results of the collaborative exercises were employed to identify possible sources of errors that could arise during the analysis and interpretation of mtDNA profiles. These findings were taken as a basis to tentatively make suitable arrangements for the construction of a high quality mtDNA database. One hundred fifty mtDNA profiles were submitted to the evaluating laboratory, and disaccording profiles were classified into four groups corresponding to the source of error: clerical errors, sample mix-ups, contaminations and discrepancies with respect to the mtDNA nomenclature. Overall, 14 disaccording haplotypes (16 individual errors) were observed. The errors included 10 clerical errors, 3 interpretation problems, 2 cases of sample mix-up and 1 case of point heteroplasmic mixture, where the 2 sequencing reactions brought inconsistent base calls. This corresponds to an error rate of 10.7% in a virtual mtDNA database consisting of the collaborative exercise results. However, this estimate is still conservative compared to conclusions drawn by authors of meanwhile numerous publications critically reviewing published mtDNA population databases. Our results and earlier published concerns strongly emphasize the need for appropriate safety regulations when mtDNA profiles are compiled for database purposes in order to accomplish the high standard required for mtDNA databases that are used in the forensic context.

Clinical Laboratory Techniques↗
PubMed2003

Cerebral c-jun expression mapping in sudden infant death syndrome.

Despite a decline in the overall rate of sudden infant death syndrome (SIDS), it remains the leading cause of postneonatal infant mortality. Research into underlying mechanisms of SIDS has still not yielded a morphological, histopathological correlate explaining aetiology and pathophysiology of an infant's sudden death. Of particular interest would be elucidating pathophysiological and molecular events immediately preceding the infant's sudden death. C-jun is an immediate early gene with a physiological role in orchestrating cellular responses following injury including a role in cell death. It is also one of the earliest and most consistent markers for neurons undergoing stress, degeneration and survival. We investigated the immunohistochemical expression of the acute phase protein c-jun within 47 separate cerebral regions of interest in the brains of 23 SIDS and 7 control cases for evidence of acute neuronal injury immediately preceding sudden death and to assess the distribution of cellular damage suggestive of pathophysiologically sensitive or critical cerebral regions. Dividing SIDS-cases and controls into subgroups with (1) no neuronal expression of c-jun at all or (2) some c-jun expression, a statistically significant higher c-jun expression for SIDS compared with control cases was established for the inferior colliculi ( P=0.008), the spinal trigeminal nuclei ( P=0.046) and the premotoric cortex layers II and IV ( P=0.029). The increased expression of c-jun in these areas might be directly related to the pathogenesis of sudden death, or may represent a secondary marker of neuronal injury with the primary event/injury being elsewhere in critical cardioventilatory circuits.

Cerebral Cortex↗
PubMed2003

Mitochondrial DNA control region diversity in hairs and body fluids of monozygotic triplets.

Length heteroplasmy of the homopolymeric cytosine stretch in the hypervariable region II of the mitochondrial D-loop was investigated in blood, buccal cells and hair shafts of monozygotic triplets. The proportions of length heteroplasmy were determined by cloning and sequencing of multiple independent clones. Blood and buccal cells showed an accumulation of molecules with one and two insertions of cytosine residues in relation to the Cambridge Reference Sequence (CRS). The results did not show statistically significant differences between blood and buccal cells of one and the same individual and also not between the three monozygotic brothers. In the hair samples a loss of cytosine residues was established in all three monozygotic individuals compared to blood and buccal cells, suggesting that this must be a regular process. Furthermore, the hair shaft samples showed significant differences between the frequencies of 7, 8 or 9 Cs in the poly C region comparing the three individuals (p<0.008) and in addition there were highly significant differences (p<0.0001) when comparing the results for six different hairs of each individual separately. From these results it can be assumed that besides a common genetic bottleneck during embryonic development, a post-embryonic bottleneck seems to exist in each hair follicle.

Adult↗
PubMed2003

Analysis of 15 short tandem repeats reveals significant differences between the Arabian populations from Morocco and Syria.

The short tandem repeat (STR) systems D3S1358, TH01, D21S11, D18S51, Penta E, D5S818, D13S317, D7S820, D16S539, CSF1PO, Penta D, vWA, D8S1179, TPOX and FGA were studied in Arabian population samples from Morocco and Syria. No significant deviation from Hardy-Weinberg equilibrium could be observed in either preparation. Comparing the Moroccan and Syrian populations using the program RxC, no similarity could be observed at all 15 loci. In the Moroccan and Syrian populations the matching probability is 1 in 1.4 x 10(17) and 1 in 2.6 x 10(17), respectively. Thus, the combination of these 15 STR loci is powerful tool for forensic identification in Arabian populations.

DNA Fingerprinting↗
PubMed2003

Utilization of lectin-histochemistry in forensic neuropathology: lectin staining provides useful information for postmortem diagnosis in forensic neuropathology.

We have investigated the deposition of glycoconjugates in human brain tissue with or without brain disorders. In this review we describe the application of lectin-histochemistry techniques to forensic neuropathology. Lectin staining is able to reveal several kinds of carbohydrate-related depositions in addition to the conventional degenerative changes including senile plaques, neurofibrillary tangles and corpora amylacea. The senile plaques and neurofibrillary tangles were clearly stained by Con A, PSA and GSI lectins, the corpora amylacea which is relevant to repeated brain hypoxia and mitochondrial damage was also easily detected by these and many other kinds of lectins. Amorphous spaces were detected around blood vessels and independently from blood vessels by lectin staining in the white matter from patients with brain disorders or severe edema. The white matter lesions were not considered relevant for forensic pathology, until a large group of cerebral white matter lesions were detected in the elderly with increasing frequency by modern neuro-imaging methods. The spherical deposits were newly detected by lectin staining in the molecular layer of the dentate gyrus of the hippocampal formation chiefly from patients with schizophrenia or cognitive dysfunctions.

Alzheimer Disease↗
PubMed2002

Natural radioactivity and human mitochondrial DNA mutations.

Radioactivity is known to induce tumors, chromosome lesions, and minisatellite length mutations, but its effects on the DNA sequence have not previously been studied. A coastal peninsula in Kerala (India) contains the world's highest level of natural radioactivity in a densely populated area, offering an opportunity to characterize radiation-associated DNA mutations. We sampled 248 pedigrees (988 individuals) in the high-radiation peninsula and in nearby low-radiation islands as a control population. We sequenced their mtDNA, and found that the pedigrees living in the high-radiation area have significantly (P < 0.01) increased germ-line point mutations between mothers and their offspring. In each mutation case, we confirmed maternity by autosomal profiling. Strikingly, the radioactive conditions accelerate mutations at nucleotide positions that have been evolutionary hot spots for at least 60,000 years.

Base Sequence↗