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T Wienker

Publications and source records attributed to T Wienker.

At least 19 recordsLinked to original sources
PubMed1999

Characterization of polymorphisms in the promoter of the human angiotensin II subtype 1 (AT1) receptor gene.

In this study eight sequence variants in the functional promoter of the human angiotensin II subtype 1 (AT1 or AGTR1) receptor gene are reported. Six of these variants are in nearly total linkage disequilibrium with each other and occur with a frequency of 15.7%. By haplotype estimation this group of eight sequence variants is characterized by only five haplotypes. There is no linkage disequilibrium between one of these haplotypes and the AT1 + 1166A/C variant. The finding of polymorphic sites in the functional promoter of the human AT1 locus will be beneficial to the study of the role of the AT1 receptor gene in hypertension and other cardiovascular diseases.

Base Sequence↗
PubMed1999

Quantitative analysis of survival motor neuron copies: identification of subtle SMN1 mutations in patients with spinal muscular atrophy, genotype-phenotype correlation, and implications for genetic counseling.

Problems with diagnosis and genetic counseling occur for patients with autosomal recessive proximal spinal muscular atrophy (SMA) who do not show the most common mutation: homozygous absence of at least exon 7 of the telomeric survival motor neuron gene (SMN1). Here we present molecular genetic data for 42 independent nondeleted SMA patients. A nonradioactive quantitative PCR test showed one SMN1 copy in 19 patients (45%). By sequencing cloned reverse-transcription (RT) PCR products or genomic fragments of SMN1, we identified nine different mutations in 18 of the 19 patients, six described for the first time: three missense mutations (Y272C, T274I, S262I), three frameshift mutations in exons 2a, 2b, and 4 (124insT, 241-242ins4, 591delA), one nonsense mutation in exon 1 (Q15X), one Alu-mediated deletion from intron 4 to intron 6, and one donor splice site mutation in intron 7 (c.922+6T-->G). The most frequent mutation, Y272C, was found in 6 (33%) of 18 patients. Each intragenic mutation found in at least two patients occurred on the same haplotype background, indicating founder mutations. Genotype-phenotype correlation allowed inference of the effect of each mutation on the function of the SMN1 protein and the role of the SMN2 copy number in modulating the SMA phenotype. In 14 of 23 SMA patients with two SMN1 copies, at least one intact SMN1 copy was sequenced, which excludes a 5q-SMA and suggests the existence of further gene(s) responsible for approximately 4%-5% of phenotypes indistinguishable from SMA. We determined the validity of the test, and we discuss its practical implications and limitations.

Cyclic AMP Response Element-Binding Protein↗
PubMed1998

The gene for human fibronectin glomerulopathy maps to 1q32, in the region of the regulation of complement activation gene cluster.

Fibronectin glomerulopathy (GFND) is a newly recognized autosomal dominant disease of the kidney that results in albuminuria, microscopic hematuria, hypertension, renal tubular acidosis type IV, and end-stage renal disease in the 2d to 6th decade of life. The disease is characterized histologically by massive deposits of fibronectin (Fn) present in the subendothelial spaces of renal glomerular capillaries. The cause of human GFND is unknown. In order to localize a candidate gene for GFND, we performed linkage analysis of a large, 193-member pedigree containing 13 affected individuals. Since we had previously excluded the genes for Fn and uteroglobin as candidate genes for GFND, a total-genome search for linkage was performed. Examination of 306 microsatellite markers resulted in a maximum two-point LOD score of 4.17 at a recombination fraction of. 00 for marker D1S249, and a maximum multipoint LOD score of 4.41 for neighboring marker D1S2782. By detection of recombination events, a critical genetic interval of 4.1 cM was identified, which was flanked by markers D1S2872 and D1S2891. These findings confirm that GFND is a distinct disease entity among the fibrillary glomerulopathies. Gene identification will provide insights into the molecular interactions of Fn in GFND, as well as in genetically unaltered conditions.

Adult↗
PubMed1998

POPSIM: a general population simulation program.

MOTIVATION: The investigation of common disorders of polygenic inheritance using both population-based association designs and non-parametric linkage analysis within families is gaining increasing importance. We have created a program that allows for the flexible simulation of populations as a tool to investigate the properties of population-based mapping approaches. RESULTS: We have created a population simulation program, POPSIM, that (i) creates a virtual representation of every individual, (ii) makes no prior assumptions but the Mendelian rules and (iii) allows populations of several million individuals in size to be generated and to be followed over hundreds of generations. The parameters of the disease model, population structure and population expansion rate can be specified. Flexible sampling options exist that allow samples of families and individuals to be drawn at any given point during the population history. The program may be a useful tool in the study of the influence of genetic drift, recombination and admixture on the generation and maintenance of linkage disequilibrium in populations, as well as the evaluation of stochastic sampling characteristics of families and individuals conditional on a complex genetic phenotype from homogeneous and heterogeneous populations. AVAILABILITY: The source code as well as Sun and Windows NT4.0 console executables of the program are available under http://www.ukrv. de/ch/medgen/html/benutzer/j.hampe/popsim. html. CONTACT: J. Hampe@mucosa.de

Computational Biology↗
PubMed1997

Localization of the gene for Wieacker-Wolff syndrome in the pericentromeric region of the X chromosome.

The Wieacker-Wolff syndrome (WWS, MIM* 314580), first described clinically in 1985, is an X-linked recessive disorder. In earlier studies, linkage between the WWS gene and DXYS1 at Xq21.2 and DXS1 at Xq11 as well as AR at Xq12 was reported. Here we report on a linkage analysis using highly polymorphic, short terminal repeat markers located in the segment from Xp21 to Xq24. No recombination between the WWS locus and ALAS2 or with AR (z = 4.890 at theta = 0.0) was found. Therefore, the WWS locus was assigned to a segment of approximately 8 cM between PFC (Xp11.3-Xp 11.23) and DXS339 (Xq11.2-Xq13).

Centromere↗
PubMed1997

Localization of the gene causing keratolytic winter erythema to chromosome 8p22-p23, and evidence for a founder effect in South African Afrikaans-speakers.

Keratolytic winter erythema (KWE), also known as "Oudtshoorn skin disease," or "erythrokeratolysis hiemalis," is an autosomal dominant skin disorder of unknown etiology characterized by a cyclical erythema, hyperkeratosis, and recurrent and intermittent peeling of the palms and soles, particularly during winter. Initially KWE was believed to be unique to South Africa, but recently a large pedigree of German origin has been identified. The disorder occurs with a prevalence of 1/7,000 in the South African Afrikaans-speaking Caucasoid population, and this high frequency has been attributed to founder effect. After a number of candidate regions were excluded from linkage to KWE in both the German family and several South African families, a genomewide analysis was embarked on. Linkage to the microsatellite marker D8S550 on chromosome 8p22-p23 was initially observed, with a maximum LOD score (Z(max)) of 9.2 at a maximum recombination fraction (theta(max)) of .0 in the German family. Linkage was also demonstrated in five of the larger South African families, with Z(max) = 7.4 at theta(max) = .02. When haplotypes were constructed, 11 of 14 South African KWE families had the complete "ancestral" haplotype, and 3 demonstrated conservation of parts of this haplotype, supporting the hypothesis of founder effect. The chromosome segregating with the disease in the German family demonstrated a different haplotype, suggesting that these chromosomes do not have a common origin. Recombination events place the KWE gene in a 6-cM interval between D8S550 and D8S552. If it is assumed that there was a single South African founder, a proposed ancestral recombinant suggests that the gene is most likely in a 1-cM interval between D8S550 and D8S265.

Chromosome Mapping↗
PubMed1996

Angiotensin-converting enzyme and heart chymase gene polymorphisms in hypertrophic cardiomyopathy.

We examined the insertion/deletion polymorphism in the angiotensin-converting enzyme gene and identified polymorphisms in the heart chymase gene to test the hypothesis that these angiotensin II-producing enzymes are associated with a monogenic cardiac disease (50 patients and 50 control subjects) as a model of cardiac hypertrophy. We found that the angiotensin-converting enzyme DD genotype was present more often in patients than in control subjects and identified a possible interaction with 1 of the chymase polymorphisms.

Adult↗
PubMed1995

'Treasure your exceptions': what we can learn from autosomal-dominant inherited forms of hypertension.

OBJECTIVE: To discuss the relevance of rare monogenic forms of hypertension to the diagnosis, pathogenesis and treatment of essential hypertension. STUDY SELECTION: Three monogenic forms of hypertension have been identified that are inherited as a simple autosomal-dominant trait. The genetic defects and the pathophysiology of two, namely glucocorticoid-remediable aldosteronism and Liddle's syndrome, have been elucidated in great detail. The third form of monogenic hypertension, which cosegregates with a second phenotype, brachydactyly, is being investigated. RESULTS: Glucocorticoid-remediable aldosteronism is caused by the presence of a chimeric gene, which incorporates the regulatory region of the 11-beta-hydroxylase gene and the structural portion of the aldosterone synthase gene. The enzyme aldosterone synthase is not only expressed in the zona fasiculata but is also regulated by adrenocorticotrophic hormone in this condition. Liddle's syndrome is caused by mutations in the beta subunit of the epithelial sodium channel. The mutations result in inappropriate channel patency and increased distal sodium reabsorption. Both of these forms of inherited hypertension are low-renin forms of hypertension. Glucocorticoid-remediable aldosteronism resembles primary aldosteronism, whereas Liddle's syndrome resembles low-renin essential hypertension. An autosomal-dominant genetic form of hypertension has been described in northeastern Turkey. The hypertension cosegregates 100% with brachydactyly. This form resembles essential hypertension, because levels of renin, aldosterone, catecholamines and other regulators are normal. Furthermore, in contrast to glucocorticoid-remediable aldosteronism and Liddle's syndrome, the patients are not salt-sensitive. CONCLUSIONS: Mechanisms of mineralcorticoid hypertension, renally induced salt-sensitive hypertension, and possibly essential hypertension, may be elucidated by studying exceptional families.

Humans↗
PubMed1993

Loss of constitutional heterozygosity on chromosome 11p in human ovarian cancer. Positive correlation with grade of differentiation.

BACKGROUND: There is increasing evidence suggesting that genes located on the short arm of chromosome 11 play an important role in the development of human ovarian cancer. Recent cytogenetic and molecular studies have demonstrated the loss of genetic material in this region. Loss of normal growth regulatory genes may allow for the expression of tumorigenicity or lead to tumor progression. METHODS: The authors used DNA recombinant techniques to examine the frequency of allelic losses at four loci spanning the chromosomal region 11p15.1-11p15.5 in 40 patients with malignant ovarian tumors. DNA extracts from normal leukocytes and 48 tumor samples were analyzed by Southern blotting using the polymorphic probes pEJ6.6 (HRAS1), phins310 (INS), p20.36 (PTH), and pEM36 (CALCA). RESULTS: Reduction to homozygosity in the tumor DNA was found in 47.5% of the informative cases (19 of 40). Comparing the results with clinical parameters, none of the well-differentiated tumors (6 of 40, Grade 1) and only one of the early stage tumors (6 of 40, International Federation of Gynecology and Obstetrics [FIGO] Stage I or II) showed alterations in this chromosome region. Statistical analysis revealed a strong correlation of rate of loss of constitutional heterozygosity (LOH) and grade of differentiation, in the sense of higher 11p allele losses occurring in poorly differentiated tumors. CONCLUSIONS: The authors concluded that the relatively high incidence of 11p allele losses marks an important step in ovarian cancer development. Furthermore, statistical analysis showed that loss of 11p alleles was strongly correlated with poorly differentiated ovarian cancer, indicating the location of genes involved in cellular functions associated with the development of more anaplastic tumors.

Adenocarcinoma↗
PubMed1989

Association and sibpair analysis for the HLA, Gm, Km, and insulin polymorphisms in multiplex IDDM families.

A log-linear model was used to analyze three-way interactions between IDDM and pairs of genetic markers. To do this, a special sample dataset was selected by taking one affected and one unaffected child from each family. Some three-way interactions were found for associations between insulin-dependent diabetes mellitus (IDDM), HLA-DR, and DQ restriction enzyme fragment length polymorphism (RFLP) patterns. No three-way interaction was found for IDDM, HLA-DR, and Gm or Km. An extended sibpair analysis was applied to the HLA-B,DR loci and to the Gm, Km, and insulin gene polymorphisms. The well-known result for IDDM and HLA was reproduced. For Gm, Km, and the insulin gene no cosegregation with IDDM could be found.

Child↗
PubMed1989

Myotonia congenita (Thomsen's disease) excluded from the region of the myotonic dystrophy locus on chromosome 19.

Linkage analysis has been carried out in six German families with autosomal dominantly inherited myotonia congenita (Thomsen's disease) using five chromosome 19 markers known to be linked to the gene for myotonic dystrophy (DM). Two of the markers, APOC1 and APOC2, are tightly linked to DM. Close linkage between these markers and myotonia congenita (MC) has been excluded to a distance of 9 cM (z = -2.158). These data support the clinical suggestion that MC and DM are non-allelic disorders.

Chromosomes, Human, Pair 19↗
PubMed1987

Linkage analysis with RFLPs in families with androgen resistance syndromes: evidence for close linkage between the androgen receptor locus and the DXS1 segment.

Three families with androgen resistance syndromes--two with testicular feminization and one with Reifenstein syndrome--have been studied for linkage analysis. Using three cloned DNA sequences from the centromere region and the proximal long arm of the X chromosome (p8, pDP34, and S9, which define respectively the chromosomal segments DXS1, DXYS1, and DXS17), we found no recombination between the DXS1 locus and the mutant genes in the three families. Assuming that these disorders are the result of allelic mutations at the same locus for the androgen receptor, we can conclude that there is a close linkage between DXS1 and the androgen receptor locus, with a maximum lod score zeta = 3.5 at a recombination fraction theta = 0.0 using the LIPED program (Ott 1974).

Androgen-Insensitivity Syndrome↗
PubMed1986

Dermatoglyphic patterns and pattern intensities of Callicebus (primates: Cebidae): description and comparison of three species.

The palmar and plantar dermatoglyphic pattern types are described for three species of Callicebus (18 Callicebus moloch, 18 Callicebus torquatus and 7 Callicebus personatus). Mean pattern intensities (API) were calculated for each of seven areas of the palm and nine areas of the sole, and a summed mean total pattern intensity (TPI) for each volar surface. Nonparametric statistical testing showed no significant bilateral asymmetry or sexual dimorphism in pattern intensities. Pattern profiles describing the relative relationships of API values across the left palm and sole are presented. The profiles typical of the genus closely resemble those of Aotus and Saimiri. Significant interspecific differences, particularly in the plantar API values, were detected. The results are discussed with reference to the present taxonomic classification of the species of Callicebus and their postulated evolutionary history.

Animals↗
PubMed1977

Haplotype analysis of the linkage group HLA-A:HAL-B:Bf and its bearing on the interpretation of the linkage disequilibrium.

The analysis of 650 HLA-A:HAL-B:Bf three-factor haplotypes revealed significant associations only between alleles of the very closely linked genes HLA-A and HLA-B, and Bf, respectively. Most striking is the highly significnat association of the rare Bf variant F1 with HLA-B18 and of S1 with HLA-B13, HLA-B14, and HLA-Bw21. Only random allele distributions were observed when considering the somewhat more distant genes HLA-A and Bf or the higher order interaction at all three genes. From these findings it seems likely that the linkage disequilibrium within the MHC is not due to selective forces, but rather due to a short evolutionary period.

Chromosomes, Human, 6-12 and X↗
PubMed1977

Adrenoleukodystrophy (Siemerling-creutzfeldt disease): Heterozygote with two clonal fibroblast populations.

On the fifth day after subcultivation,, fibroblasts of two unrelated patients with adrenoleukodystrophy (Siemerling-Creutzfeldt disease (SCD)) developed typical morphologic anomalies which could be seen by light microscopy. From skin biopsy material of an obligatorily heterozygous womam, both normal and morphologically defective colonies could be isolated. These findings suggest that the morphologic alterations are an expression of the defect in Siemerling-Creutzfeldt disease. Futhermore, they suggest that the SCD locus is subject to lyonization.

Adrenal Cortex Diseases↗