Publikationen von Andreas Wolf
Lieb W, Jacobs G, Wolf A, Richter G, Gaede KI, Schwarz J, Arnold N, Böhm R, Buyx A, Cascorbi I, Franke A, Glinicke C, Held-Feindt J, Junker R, Kalthoff H, Kramer HH, Leypoldt F, Maass N, Maetzler W, May S, Mehdorn HM, Röcken C, Schafmayer C, Schrappe M, Schreiber S, Sebens S, Stephani U, Synowitz M, Weimer J, Zabel P, Nöthlings U, Röder C, Krawczak M.
Linking pre-existing biorepositories for medical research: the PopGen 2.0 Network.J Community Genet,
(2019).
[abstract]
Abstract:
The significance of human biorepositories for modern medical research, particularly for comprehensive population-based genetic analyses, is constantly growing. While large and centralized institutions are usually considered best suited to meet the increasing demand for high-quality "biobanks," most medical research institutions still host rather heterogeneous and fragmented biobanking activities, undertaken by clinical departments with oftentimes rather different scientific scope. Undoubtedly, most clinicians and medical researchers would appreciate infrastructural support in terms of the storage and handling of their biosamples, but they are also likely to expect access to their samples avoiding extensive formal requirements. We report on the establishment of the PopGen 2.0 Network (P2N), an overarching alliance of initially seven biobanks from Northern Germany which adopted a joint but lean governance structure and use-and-access policy for their samples and data. In addition, the members of P2N have pursued an intense collaboration on ethical, legal and social issues and maintain a common IT infrastructure. The implementation of P2N has substantially improved the prospects of biobank-based research at the participating institutions. The network may thus serve as a role model for similar initiatives geared at linking pre-existing biorepositories for the benefit of research quality, efficiency, and transparency.
Schuster M, Tittmann L, Wolf A.
Predicting Matching Quality of Record Linkage Algorithms on Growing Data Sets.Stud Health Technol Inform,
253 (2018), 70-74.
[abstract]
Abstract:
A record linkage algorithm tries to identify records which belong to the same individual. We analyze the matching behavior of an approach used in the E-PIX matching tool on the very limited attribute set of first name, last name, date of birth and sex. Our benchmark set contains almost 37,000 records from the Popgen biobank. We develop a model which allows us to predict the workload on clerical review for data sets growing up to a factor of 10 or even more, without the need for a data set of this size. Based on this model we show two parameter sets with comparable detection rate of true duplicates, but where only one of them scales well on growing data sets. Our model provides realistic example records for each predicted matching of an upscaled data set. Thus, it enables to identify the parameters which need to be adjusted in order to improve the quality of the matching candidates. We also show that unreviewed merging of records is prone to homonym errors on data sets with 200,000 records and the limited attribute set above, while the merged record pairs are obviously different in clerical review.
Jacobs G, Wolf A, Krawczak M, Lieb W.
Biobanks in the Era of Digital Medicine.Clin Pharmacol Ther,
(2017).
[abstract]
Abstract:
Digitalization is currently permeating virtually all sectors of modern societies, including biomedical research and medical care. At the same time, biobanks engaged in the long-term storage of biological samples that are fit for purpose have become key drivers in both fields. The present article highlights some of the challenges and opportunities that biobanking is facing in the current proverbial "era of digitalization."
Wolf A, Jacobs G, Kovalov G, Malin C, Wähnert M, Bieling D, Stephan C.
CentraXX spricht Kiwi – Integration eines vollautomatischen Probenlagers.5. Nationales Biobanken-Symposium 2015 – Tagungsband,
5 (2016).
Siegert S, Wolf A, Cooper DN, Krawczak M, Nothnagel M.
Mutations Causing Complex Disease May under Certain Circumstances Be Protective in an Epidemiological Sense.PLoS One,
10 (2015), e0132150.
[abstract]
Abstract:
Guided by the practice of classical epidemiology, research into the genetic basis of complex disease has usually taken for granted the dictum that causative mutations are invariably over-represented among clinically affected as compared to unaffected individuals. However, we show that this supposition is not true and that a mutation contributing to the etiology of a complex disease can, under certain circumstances, be depleted among patients. Populations with defined disease prevalence were repeatedly simulated under a Wright-Fisher model, assuming various types of population history and genotype-phenotype relationship. For each simulation, the resulting mutation-specific population frequencies and odds ratios (ORs) were evaluated. In addition, the relationship between mutation frequency and OR was studied using real data from the NIH GWAS catalogue of reported phenotype associations of single-nucleotide polymorphisms (SNPs). While rare diseases (prevalence <1%) were found to be consistently caused by rare mutations with ORs>1, up to 20% of mutations causing a pandemic disease (prevalence 10-20%) had ORs<1, and their population frequency ranged from 0% to 100%. Moreover, simulation-based ORs exhibited a wide distribution, irrespective of mutation frequency. In conclusion, a substantial proportion of mutations causing common complex diseases may appear 'protective' in genetic epidemiological studies and hence would normally tend to be excluded, albeit erroneously, from further study. This apparently paradoxical result is explicable in terms of mutual confounding of the respective genotype-phenotype relationships due to a negative correlation between causal mutations induced by their common gene genealogy. As would be predicted by our findings, a significant negative correlation became apparent in published genome-wide association studies between the OR of genetic variants associated with a particular disease and the prevalence of that disease.
Lieb W, Jacobs B, Wolf A, Krawczak M.
Biobanking für klinische und populationsbasierte Forschungsfragen: Erfahrungen aus Kiel.4. Nationales Biobanken-Symposium 2015 – Tagungsband,
4 (2015).
Kirch P, Lieb W, Wolf A.
Das „PopGen Portal“ für Rollen- und Regelbasiertes Online Biobanking.3. Nationales Biobanken-Symposium 2014 – Tagungsband,
3 (2014).
Wolf A, Hemmrich-Stanisak G, Werberger S, Günsel A, Franke A, Lieb W, Krawczak M.
Kiel auf dem Weg zur Integration von Biomaterialien und Forschungsdaten.2. Nationales Biobanken-Symposium 2013 – Tagungsband,
2 (2013).
Taudien S, Gäbel G, Kuss O, Groth M, Grützmann R, Huse K, Kluttig A, Wolf A, Nothnagel M, Rosenstiel P, Greiser KH, Werdan K, Krawczak M, Pilarsky C, Platzer M.
Association studies of the copy-number variable Ss-defensin cluster on 8p23.1 in adenocarcinoma and chronic pancreatitis.BMC Res Notes,
5 (2012), 629.
[abstract]
Abstract:
ABSTRACT: BACKGROUND: Human Ss-defensins are a family of antimicrobial peptides located at the mucosal surface. Both sequence multi-site variations (MSV) and copy-number variants (CNV) of the defensin-encoding genes are associated with increased risk for various diseases, including cancer and inflammatory conditions such as psoriasis and acute pancreatitis. In a case--control study, we investigated the association between MSV in DEFB104 as well as defensin gene (DEF) cluster copy number (CN), and pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). RESULTS: Two groups of PDAC (N=70) and CP (N=60) patients were compared to matched healthy control groups CARLA1 (N=232) and CARLA2 (N=160), respectively. Four DEFB104 MSV were haplotyped by PCR, cloning and sequencing. DEF cluster CN was determined by multiplex ligation-dependent probe amplification.Neither the PDAC nor the CP cohorts show significant differences in the DEFB104 haplotype distribution compared to the respective control groups CARLA1 and CARLA2, respectively.The diploid DEF cluster CN exhibit a significantly different distribution between PDAC and CARLA1 (Fisher's exact test P=0.027), but not between CP and CARLA2 (P=0.867). CONCLUSION: Different DEF cluster b CN distribution between PDAC patients and healthy controls indicate a potential protective effect of higher CNs against the disease.
Wolf A, Caliebe A, Thomas NS, Ball EV, Mort M, Stenson PD, Krawczak M, Cooper DN.
Single base-pair substitutions at the translation initiation sites of human genes as a cause of inherited disease.Hum Mutat,
32 (2011), 1137–43.
[abstract]
Abstract:
A total of 405 unique single base-pair substitutions, located within the ATG translation initiation codons (TICs) of 255 different genes, and reported to cause human genetic disease, were retrieved from the Human Gene Mutation Database (HGMD). Although these lesions comprised only 0.7% of coding sequence mutations in HGMD, they nevertheless were 3.4-fold over-represented as compared to other missense mutations. The distance between a TIC and the next downstream in-frame ATG codon was significantly greater for genes harbouring TIC mutations than for the remainder of genes in HGMD ('control genes'). This suggests that the absence of an alternative ATG codon in the vicinity of a TIC increases the likelihood that a given TIC mutation will come to clinical attention. An additional 42 single base-pair substitutions in 37 different genes were identified in the vicinity of TICs (positions -6 to +4, comprising the so-called 'Kozak consensus sequence'). These substitutions were not evenly distributed, being significantly more abundant at position +4. Finally, contrary to our initial expectation, the match between the original TIC and the Kozak consensus sequence was significantly better (rather than worse) for genes harbouring TIC mutations than for the HGMD control genes. © 2011 Wiley-Liss, Inc.
Nothnagel M, Herrmann A, Wolf A, Schreiber S, Platzer M, Siebert R, Krawczak M, Hampe J.
Technology-specific error signatures in the 1000 Genomes Project data.Hum Genet,
(2011).
[abstract]
Abstract:
Next-generation sequencing (NGS) will likely facilitate a better understanding of the causes and consequences of human genetic variability. In this context, the validity of NGS-inferred single-nucleotide variants (SNVs) is of paramount importance. We therefore developed a statistical framework to assess the fidelity of three common NGS platforms. Using aligned DNA sequence data from two completely sequenced HapMap samples as included in the 1000 Genomes Project, we unraveled remarkably different error profiles for the three platforms. Compared to confirmed HapMap variants, newly identified SNVs included a substantial proportion of false positives (3-17%). Consensus calling by more than one platform yielded significantly lower error rates (1-4%). This implies that the use of multiple NGS platforms may be more cost-efficient than relying upon a single technology alone, particularly in physically localized sequencing experiments that rely upon small error rates. Our study thus highlights that different NGS platforms suit different practical applications differently well, and that NGS-based studies require stringent data quality control for their results to be valid.
Wolf A, Lu TT.
Datenstrukturen, Speicherung und Transfer von Genotypisierungsdaten.Qualitätsmanagement von Hochdurchsatz-Genotypisierungsdaten,
(2011).
Nothnagel M, Wolf A, Herrmann A, Szafranski K, Vater I, Brosch M, Huse K, Siebert R, Platzer M, Hampe J, Krawczak M.
Statistical inference of allelic imbalance from transcriptome data.Hum Mutat,
(2010).
[abstract]
Abstract:
Next-generation sequencing and the availability of high-density genotyping arrays have facilitated an analysis of somatic and meiotic mutations at unprecedented level, but drawing sensible conclusions about the functional relevance of the detected variants still remains a formidable challenge. In this context, the study of allelic imbalance in intermediate RNA phenotypes may prove a useful means to elucidate the likely effects of DNA variants of unknown significance. We developed a statistical framework for the assessment of allelic imbalance in next-generation transcriptome sequencing (RNA-seq) data that requires neither an expression reference nor the underlying nuclear genotype(s), and that allows for allele miscalls. Using extensive simulation as well as publicly available whole-transcriptome data from European-descent individuals in HapMap, we explored the power of our approach in terms of both genotype inference and allelic imbalance assessment under a wide range of practically relevant scenarios. In so doing, we verified a superior performance of our methodology, particularly at low sequencing coverage, compared to the more simplistic approach of completely ignoring allele miscalls. Since the proposed framework can be used to assess somatic mutations and allelic imbalance in one and the same set of RNA-seq data, it will be particularly useful for the analysis of somatic genetic variation in cancer studies. © 2010 Wiley-Liss, Inc.
Fiebig A, Krusche P, Wolf A, Krawczak M, Timm B, Nikolaus S, Frings N, Schreiber S.
Heritability of chronic venous disease.Hum Genet,
(2010).
[abstract]
Abstract:
Varicose veins without skin changes have a prevalence of approximately 20% in Northern and Western Europe whereas advanced chronic venous insufficiency affects about 3% of the population. Genetic risk factors are thought to play an important role in the aetiology of both these chronic venous diseases (CVD). We evaluated the relative genetic and environmental impact upon CVD risk by estimating the heritability of the disease in 4,033 nuclear families, comprising 16,434 individuals from all over Germany. Upon clinical examination, patients were classified according to the CEAP guidelines as either C2 (simple varicose veins), C3 (oedema), C4 (skin changes without ulceration), C5 (healed ulceration), or C6 (active ulcers). The narrow-sense heritability (h (2)) of CVD equals 17.3% (standard error 2.5%, likelihood ratio test P = 1.4 x 10(-13)). The proportion of disease risk attributable to age (at ascertainment) and sex, the two main risk factors for CVD, was estimated as 10.7% (Kullback-Leibler deviance R (2)). The heritability of CVD is high, thereby suggesting a notable genetic component in the aetiology of the disease. Systematic population-based searches for CVD susceptibility genes are therefore warranted.
Wolf A, Millar DS, Caliebe A, Horan M, Newsway V, Kumpf D, Steinmann K, Chee IS, Lee YH, Mutirangura A, Pepe G, Rickards O, Schmidtke J, Schempp W, Chuzhanova N, Kehrer-Sawatzki H, Krawczak M, Cooper DN.
A gene conversion hotspot in the human growth hormone (GH1) gene promoter.Hum Mutat,
30 (2009), 239-247.
[abstract]
Abstract:
To assess the evolutionary importance of nonallelic (or interlocus) gene conversion for the highly polymorphic human growth hormone (GH1) gene promoter, sequence variation in this region was studied in four different ethnic groups. For 14 SNPs in the proximal GH1 promoter (535 bp), 60 different haplotypes were observed in 577 individuals (156 Britons, 116 Spaniards, 163 West-Africans, 142 Asians). Using a novel coalescence-based statistical test, significant evidence was found in the British, Spanish, and African groups for GH1 having acted as an acceptor of gene conversion, with at least one of the four paralogous GH gene promoters serving as the donor (and specifically GH2 in the Britons and Spaniards). The average gene conversion tract length was estimated to be 84 bp. A gene conversion hotspot was identified, spanning the GH1 transcriptional initiation site (positions -6 to +25). Although these findings serve to highlight the importance of gene conversion for the recent evolution of the human GH1 promoter, its relative frequency does not appear to be related simply to the presence of specific DNA sequence motifs or secondary structures, the degree of homology between GH paralogs, the distance between them, or their transcriptional orientation. The GH1 promoter was also found to be highly polymorphic in chimpanzee but not in macaque. This may reflect the lower degree of pair-wise similarity between the GH1 promoter and its paralogs in macaque (mean, 92.0%) as compared to chimpanzee (93.5%) and human (94.0%), and hence provides further support for the idea of a threshold (perhaps around 92%) below which gene conversion is reduced or abolished. Hum Mutat 0,1-9, 2008. (c) 2008 Wiley-Liss, Inc.
Bosy-Westphal A, Wolf A, Bührens F, Hitze B, Czech N, Mönig H, Selberg O, Settler U, Pfeuffer M, Schrezenmeir J, Krawczak M, Müller MJ.
Familial influences and obesity-associated metabolic risk factors contribute to the variation in resting energy expenditure: the Kiel Obesity Prevention Study.Am J Clin Nutr,
87 (2008), 1695-701.
[abstract]
Abstract:
BACKGROUND: A low metabolic rate may be inherited and predispose to obesity, whereas a higher metabolic rate in obesity may be acquired by obesity-associated cardiometabolic risk. OBJECTIVE: We aimed to explain the interindividual variation in resting energy expenditure (REE) by assessing 1) the association between REE and body composition, thyroid hormones, and obesity-related cardiometabolic risk factors, and 2) the familial (genetic and environmental) contribution to REE. DESIGN: REE and metabolic risk factors (ie, blood pressure and plasma insulin, glucose, and C-reactive protein concentrations) were assessed in 149 two- or three-generation families, including at least one overweight or obese member. Heritability of REE, respiratory quotient (RQ), thyroid hormones [thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4)], and body composition (fat-free mass and fat mass) were estimated by using variance components-based quantitative genetic models. RESULTS: REE adjusted for body composition, sex, and age (REEadj) significantly correlated with systolic and diastolic blood pressure, plasma insulin and glucose concentrations, and the homeostasis model assessment (HOMA) (r = 0.14-0.31, P < 0.05). Thyroid hormones had a modest influence on REE variance only. Heritability was 0.30 +/- 0.07 for REEadj and 0.29 +/- 0.08 for REE after additional adjustment for thyroid hormones and metabolic risk. Furthermore, heritability was estimated to be 0.22 +/- 0.08 for RQ, 0.37 +/- 0.08 for TSH, 0.68 +/- 0.06 for FT4, and 0.69 +/- 0.05 for FT3 (all significantly larger than zero). CONCLUSIONS: Obesity-related cardiometabolic risk factors contribute to interindividual variation in REE, with hypertension and insulin resistance being associated with a higher REE. REE was moderately heritable, independent of body composition, sex, age, thyroid function, and cardiometabolic risk.
Kirsch S, Pasantes J, Wolf A, Bogdanova N, Muench C, Pennekamp P, Krawczak M, Dworniczak B, Schempp W.
Chromosomal evolution of the PKD1 gene family in primates.BMC Evol Biol,
8 (2008), 263.
[abstract]
Abstract:
ABSTRACT: BACKGROUND: The autosomal dominant polycystic kidney disease (ADPKD) is mostly caused by mutations in the PKD1 (polycystic kidney disease 1) gene located in 16p13.3. Moreover, there are six pseudogenes of PKD1 that are located proximal to the master gene in 16p13.1. In contrast, no pseudogene could be detected in the mouse genome, only a single copy gene on chromosome 17. The question arises how the human situation originated phylogenetically. To address this question we applied comparative FISH-mapping of a human PKD1-containing genomic BAC clone and a PKD1-cDNA clone to chromosomes of a variety of primate species and the dog as a non-primate outgroup species. RESULTS: Comparative FISH with the PKD1-cDNA clone clearly shows that in all primate species studied distinct single signals map in subtelomeric chromosomal positions orthologous to the short arm of human chromosome 16 harbouring the master PKD1 gene. Only in human and African great apes, but not in orangutan, FISH with both BAC and cDNA clones reveals additional signal clusters located proximal of and clearly separated from the PKD1 master genes indicating the chromosomal position of PKD1 pseudogenes in 16p of these species, respectively. Indeed, this is in accordance with sequencing data in human, chimpanzee and orangutan. Apart from the master PKD1 gene, six pseudogenes are identified in both, human and chimpanzee, while only a single-copy gene is present in the whole-genome sequence of orangutan. The phylogenetic reconstruction of the PKD1-tree reveals that all human pseudogenes are closely related to the human PKD1 gene, and all chimpanzee pseudogenes are closely related to the chimpanzee PKD1 gene. However, our statistical analyses provide strong indication that gene conversion events may have occurred within the PKD1 family members of human and chimpanzee, respectively. CONCLUSION: PKD1 must have undergone amplification very recently in hominid evolution. Duplicative transposition of the PKD1 gene and further amplification and evolution of the PKD1 pseudogenes may have arisen in a common ancestor of Homo, Pan and Gorilla ~ 8 MYA. Reticulate evolutionary processes such as gene conversion and non-allelic homologous recombination (NAHR) may have resulted in concerted evolution of PKD1 family members in human and chimpanzee and, thus, simulate an independent evolution of the PKD1 pseudogenes from their master PKD1 genes in human and chimpanzee.
Bosy-Westphal A, Onur S, Geisler C, Wolf A, Korth O, Pfeuffer M, Schrezenmeir J, Krawczak M, Müller MJ.
Common familial influences on clustering of metabolic syndrome traits with central obesity and insulin resistance: the Kiel obesity prevention study.Int J Obes (Lond),
31 (2007), 784-90.
[abstract]
Abstract:
OBJECTIVE: The phenotypic heterogeneity of metabolic syndrome (MSX) suggests heterogeneity of the underlying genotype. The aim of the present study was to examine the common genetic background that contributes to the clustering between the two main features (insulin resistance, central obesity) and different MSX component traits. METHODS: In all, 492 individuals from 90 families were investigated in a three-generation family path study as part of the Kiel Obesity Prevention Study (KOPS, 162 grandparents, 66.1+/-6.7 years, 173 parents, 41.3+/-5.4 years and 157 children, 10.8+/-3.4 years). Overall heritability was estimated and common familial (genetic and environmental) influences on insulin resistance (HOMA-IR) or central obesity (elevated waist circumference, WC), respectively, and different MSX traits were compared in a bivariate cross-trait correlation model. RESULTS: Prevalence of MSX (according to NCEP criteria) was 27.2% (f) and 27.8% (m) in adults and 3.5% (f) and 8.5% (m) in children and adolescents, respectively. MSX phenotype was found to be highly variable, comprising 16 subtypes of component trait combinations. Within-trait heritability was 38.5% for HOMA-IR and 53.5% for WC, cross-trait heritability was 53.4%. As much as 6-18% and 3-10% of the shared variance between different MSX component traits (lipid profile, blood pressure) and WC or HOMA-IR, respectively, may be genetic. With the exception of HDL-C, the shared genetic variance between MSX component traits and WC was higher than the genetic variance shared with HOMA-IR. CONCLUSION: A common genetic background contributes to the clustering of different MSX component traits and central obesity or insulin resistance. Common genetic influences favour central obesity as a major characteristic linking these traits.
von Eller-Eberstein H, Gundermann L, Krawczak M, Schreiber S, Wolf A.
Datenmanagement bei popgen.LNI,
93 (2006), 729-735.
Steffens M, Lamina C, Illig T, Bettecken T, Vogler R, Entz P, Suk EK, Toliat MR, Klopp N, Caliebe A, König IR, Köhler K, Ludemann J, Diaz Lacava A, Fimmers R, Lichtner P, Ziegler A, Wolf A, Krawczak M, Nūrnberg P, Hampe J, Schreiber S, Meitinger T, Wichmann HE, Roeder K, Wienker TF, Baur MP.
SNP-based analysis of genetic substructure in the German population.Hum Hered,
62 (2006), 20-9.
[abstract]
Abstract:
OBJECTIVE: To evaluate the relevance and necessity to account for the effects of population substructure on association studies under a case-control design in central Europe, we analysed three samples drawn from different geographic areas of Germany. Two of the three samples, POPGEN (n = 720) and SHIP (n = 709), are from north and north-east Germany, respectively, and one sample, KORA (n = 730), is from southern Germany. METHODS: Population genetic differentiation was measured by classical F-statistics for different marker sets, either consisting of genome-wide selected coding SNPs located in functional genes, or consisting of selectively neutral SNPs from 'genomic deserts'. Quantitative estimates of the degree of stratification were performed comparing the genomic control approach [Devlin B, Roeder K: Biometrics 1999;55:997-1004], structured association [Pritchard JK, Stephens M, Donnelly P: Genetics 2000;155:945-959] and sophisticated methods like random forests [Breiman L: Machine Learning 2001;45:5-32]. RESULTS: F-statistics showed that there exists a low genetic differentiation between the samples along a north-south gradient within Germany (F(ST)(KORA/POPGEN): 1.7 . 10(-4); F(ST)(KORA/SHIP): 5.4 . 10(-4); F(ST)(POPGEN/SHIP): -1.3 . 10(-5)). CONCLUSION: Although the F(ST )-values are very small, indicating a minor degree of population structure, and are too low to be detectable from methods without using prior information of subpopulation membership, such as STRUCTURE [Pritchard JK, Stephens M, Donnelly P: Genetics 2000;155:945-959], they may be a possible source for confounding due to population stratification.
Wolf A, Caliebe A, Junge O, Krawczak M.
Forensic interpretation of Y-chromosomal DNA mixtures.Forensic Sci Int,
152 (2005), 209-13.
[abstract]
Abstract:
The mathematical concept previously introduced for the forensic interpretation of DNA mixtures using non-associated genetic markers has been adapted to the assessment of haplotypes. Such calculus is required, for example, when Y-chromosomal markers are used in forensics. In addition to outlining the general mathematical framework, we devise two approaches to its practical computational implementation, involving either the inclusion-exclusion principle of probability theory or a recursion in the number of unknown contributors invoked. The two approaches scale differently, depending upon the complexity of the case and the diversity of the markers used. The performance of Y-chromosomal microsatellites (Y-STRs) as a means of trace donor discrimination has been assessed by simulation, using the derived formulas. Based upon data from the Y-chromosomal Haplotype Reference Database (YHRD), the exclusion chance of a non-contributor is shown to vary between 95% in the case of two contributors, and 70% for five contributors. With only one additional contributor, half of all contributing suspects would yield a log-likelihood ratio in favour of donorship of 1.61 or higher, although the median drops to 0.66 with four additional contributors. It must be emphasised that these estimates of the discriminatory power of Y-STRs are likely to be conservative since the simulations involved only haplotypes known to occur in YHRD.
Langmaack H, Wolf A.
Reading and Printing in Constructing Fully Verified Compilers.Technical Report TF/CAU,
0306 (2003).
Wieland I, Jakubiczka S, Muschke P, Wolf A, Gerlach L, Krawczak M, Wieacker P.
Mapping of a further locus for X-linked craniofrontonasal syndrome.Cytogenet Genome Res,
99 (2002), 285-8.
[abstract]
Abstract:
Craniofrontonasal syndrome is a rare dysostosis syndrome with an unusual pattern of X-linked inheritance, because males are usually not or less severely affected than females. Previously, a CFNS locus has been localised in Xp22. We report on a haplotype analysis in a German CFNS family, mapping the CFNS locus to the pericentromeric region of the X chromosome. This discrepancy can be explained by locus heterogeneity. Furthermore, random X inactivation could be demonstrated in affected females. The most plausible interpretation for this unusual pattern of X-linked inheritance is metabolic interference. Consequently, we propose that the CFNS gene escapes X inactivation.
Wolf A.
Weakest Relative Precondition Semantics - Balancing Approved Theory and Realistic Translation Verification.Technical Report TF/CAU,
2013 (2001).
Müller-Olm M, Wolf A.
On Translation of Procedures to Finite Machines: Abstraction Allows a Clean Proof .LNCS,
1782 (2000).
Wolf A.
The Adequacy of a Loop's Definition.Verifix Report TF/CAU,
6.2 (1999).
Müller-Olm M, Wolf A.
On Excusable and Inexusable Failures: Looking for an Adequate Notion of Translation Correctness .LNCS,
1709 (1999).
Wolf A.
An Exercise in Compiler Verification Revisited – Preserving Partial Correctness.Verifix Report TF/CAU,
6.1 (1999).
Berghammer R, von Karger B, Wolf A.
Relation-algebraic derivation of spanning tree algorithms .LNCS,
1422 (1998).
