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U Thies

Publications and source records attributed to U Thies.

At least 19 recordsLinked to original sources
PubMed1997

The human hepatocyte nuclear factor 3/fork head gene FKHL13: genomic structure and pattern of expression.

We describe the isolation and characterization of the cDNA for FKHL13, the human homologue of the mouse hepatocyte nuclear factor 3/fork head homologue 4 (HFH-4) gene, a member of the HNF-3/fork head (also called winged helix) gene family. Members of this gene family contain a conserved DNA binding region of approx. 110 amino acids and are thought to play an important role in cell-specific differentiation. Previous analysis of the mouse and rat HFH-4 cDNAs revealed a distinct pattern of expression for this gene, suggesting that the gene plays an important role in the differentiation of lung and oviduct/ampulla epithelial cells and testicular spermatids. Analysis of the human FKHL13 gene confirmed this pattern of expression. We also found expression in adult human brain cortex, which we were able to confirm for the mouse. The expression pattern of FKHL13/HFH-4, confined to cilia/flagella-producing cells, leads us to believe that the gene plays an important role in the regulation of axonemal structural proteins. We show that the human gene for FKHL13 lies on chromosome 17 (comparison with the chromosomal location of the mouse gene strongly suggests 17q22-q25) and that the gene, which is approx. 6 kb, contains a single intron disrupting the fork head DNA binding domain. Such a disruption of a functional unit provides strong evidence for the theory of intron insertion during gene evolution. The expression of the gene is probably controlled by the CpG island, which is located in the promoter region of the gene. We also demonstrate that the FKHL13 gene is highly conserved among a wide variety of species, including birds.

Adult↗
PubMed1997

The novel human HNF-3/fork head-like 5 gene: chromosomal localization and expression pattern.

Analysis of cDNA clones, isolated from a human fetal brain cDNA library, that hybridized with the rat HNF-3 alpha fork head homolog domain revealed the 3.6-kb HFKL5 cDNA. The transcript of HFKL5 is 4.4 kb long and represents a novel member of the HNF-3/fork head transcription factor family. Comparison of the amino acid sequence of the fork head domain reveals a relatively low level of homology to other members of this family of genes, the closest related sequence being rat HFH7 with 68% homology. The HFKL5 cDNA codes for a putative 500-amino-acid protein. Southern analysis revealed that the HFKL5 gene homolog is present as a single copy in the human genome. Zoo Southern analysis showed strong evolutionary conservation of HFKL5 among mammalian and possibly avian species. Expression of HFKL5 in neurons is restricted to the fully differentiated neurons in fetal and adult brain as well as in the parasympathic ganglia of the small intestine. We also observed expression in lymphocytes, kidney tubule cells, and a subset of hepatocytes. The HFKL5 gene homolog was mapped to chromosome 22q13-qter by cell panel hybridization.

Adult↗
PubMed1996

[Huntington chorea. Molecular genetic principles, mutation detection and predictive diagnosis].

Predictive genetic testing offers the opportunity for persons at risk to obtain information about their carrier status concerning Huntington's disease (HD). HD is associated with the expansion of a (CAG) repeat in the gene IT15. HD chromosomes contain about 40-75 repeat units, whereas normal chromosomes show a range between 11 and 33 repeats. The HD repeat is highly unstable during transmission, involving both increases and decreases in size with the largest expansions occurring in male meioses. The number of (CAG) copies is inversely correlated with the onset age of the disorder. Investigation of sporadic cases revealed that new mutations for HD are more frequent than estimated. Analysis of the repeat length allows direct DNA diagnosis of affected individuals and asymptomatic persons at risk. From 1989 to March 1993 in our institute predictive testing by indirect DNA methods was requested by 108 persons at risk. After cloning of the HD gene in 1993, direct testing was requested by 113 persons at risk between April 1993 and April 1994 in Göttingen. In about 400 patients differential diagnosis was performed with the direct method. In approximately 82% of the patients the expanded (CAG) repeat was found, and the HD diagnosis could be confirmed.

Adult↗
PubMed1995

The genes for human brain factor 1 and 2, members of the fork head gene family, are clustered on chromosome 14q.

Brain factor-1 (BF-1) is a member of the fork head gene family which shows expression restricted to the neurons of the developing telencephalon in rodents and man. We have isolated a second human gene (HBF-2), which is also strongly expressed in embryonic brain and has very high homology to both the rat and human brain factor-1 genes and the retroviral oncogene qin. The HBF-2 cDNA was isolated from a human fetal brain expression library and contains a putative open reading frame of 479 amino acids. The HBF-2 gene is strongly expressed in fetal brain and also with lower levels of expression in several adult tissues. At the genomic level the gene for HBF-1 contains an 500 bp intron situated between the DNA binding domain II and the fork head domain while that of HBF-2 is intronless. The two genes are clustered on human chromosome 14q11-13.

Amino Acid Sequence↗
PubMed1994

Precise mapping of the brain alpha 2-adrenergic receptor gene within chromosome 4p16.

The gene encoding the brain alpha 2-adrenergic receptor (ADRA2C) is located on human chromosome 4. It has been circumstantially associated with a number of human disorders, including Parkinson disease, panic disorders, and Huntington disease (HD). Using somatic cell hybrids, we localized the gene to chromosome 4p16 distal to P8 (D4S62). To investigate this locus further, we isolated several cosmid clones covering the entire gene. The gene was found to be intronless. Two (GT)n repeats in close proximity to the ADRAC2 gene were analyzed and used to define its precise location. Linkage disequilibrium studies of one microsatellite in HD families showed strong nonrandom association to the HD mutation, indicating its tight linkage to the HD gene. The investigation of families carrying recombinant chromosomes, pulsed-field analysis, and genomic walking mapped the ADRA2C gene adjacent to D4S81, 500 kb proximal to the HD gene. The newly defined microsatellites at the ADRAC2 locus, its precise localization within 4p16, and the detailed PCR conditions facilitate the identification of any defect caused by this gene.

Base Sequence↗
PubMed1994

Human brain factor 1, a new member of the fork head gene family.

Analysis of cDNA clones that cross-hybridized with the fork head domain of the rat HNF-3 gene family revealed 10 cDNAs from human fetal brain and human testis cDNA libraries containing this highly conserved DNA-binding domain. Three of these cDNAs (HFK1, HFK2, and HFK3) were further analyzed. The cDNA HFK1 has a length of 2557 nucleotides and shows strong homology at the nucleotide level (91.2%) to brain factor 1 (BF-1) from rat. The HFK1 cDNA codes for a putative 476 amino acid protein. The homology to BF-1 from rat in the coding region at the amino acid level is 87.5%. The fork head homologous region includes 111 amino acids starting at amino acid 160 and has a 97.5% homology to BF-1. Southern hybridization revealed that HFK1 is highly conserved among mammalian species and possibly birds. Northern analysis with total RNA from human tissues and poly(A)-rich RNA from mouse revealed a 3.2-kb transcript that is present in human and mouse fetal brain and in adult mouse brain. In situ hybridization with sections of mouse embryo and human fetal brain reveals that HFK1 expression is restricted to the neuronal cells in the telencephalon, with strong expression being observed in the developing dentate gyrus and hippocampus. HFK1 was chromosomally localized by in situ hybridization to 14q12. The cDNA clones HFK2 and HFK3 were analyzed by restriction analysis and sequencing. HFK2 and HFK3 were found to be closely related but different from HFK1. Therefore, it would appear that HFK1, HFK2, HFK3, and BF-1 form a new fork head related subfamily.

Amino Acid Sequence↗
PubMed1994

Valid parameters for investigation of the pupillary light reflex in normal and diabetic subjects shown by factor analysis and partial correlation.

Pupillary test data of 103 normal and 119 diabetic subjects (47 IDDM, 72 NIDDM) were evaluated by factor analysis. From a total of nine pupillary parameters three factors were extracted in the analysis. Factor 1 represents maximal pupillary area, contraction velocity at 1 s, dilation velocity at 6 s and minimal pupillary area--static and simple dynamic parameters; factor 2 amplitude of pupillary unrest, area under the detrended curve of pupillary unrest and period of pupillary unrest--parameters of pupillary unrest; factor 3 fusion frequency of pupillary response following flicker stimuli and latency time of pupillary light reflex--second order dynamic parameters. Factor analysis was then applied to investigate diabetic patients with a high percentage of autonomic neuropathic participants (about 39% had pupillary and about 35% had cardiorespiratory function disorders), which revealed the same three factors as those identified in normal subjects. Furthermore, an age-related database of parameters of pupillary unrest is given. It demonstrates that normal subjects and diabetic patients did not differ in the period of pupillary unrest (normal vs diabetic (mean +/- SEM): 1550 +/- 29 vs 1536 +/- 27 ms; 2p > 0.5). The difference in amplitude (47.8 +/- 2.8 vs 41.0 +/- 2.6% percentile; 2p = 0.071) and area under the detrended curve of pupillary unrest (47.9 +/- 2.8 vs 40.8 +/- 2.6% percentile, 2p = 0.062) seems to show a trend but was not significant. In conclusion, factor analysis revealed three different pupillary test factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Down syndrome and male fertility: PCR-derived fingerprinting, serological and andrological investigations.

Down syndrome, the most common birth defect causing mental retardation, is characterized by a specific phenotype including subfertility or sterility and hypogonadism in males. In contrast, several females with Down syndrome have borne offspring. Here, a male with trisomy 21 fathering an infant is described. This observation is verified by serological markers, DNA fingerprinting using different DNA micro- or minisatellites and andrological investigations.

Adult↗
PubMed1994

A multilocus DNA fingerprint with built-in security devices.

An unusual case of paternity testing is reported in which determination of paternity was an essential part of a genetic diagnosis. A Y-chromosomal abnormality, observed in a 33-year-old male whose wife had experienced a series of spontaneous abortions, was not found in his alleged father. DNA fingerprinting with the oligonucleotide multilocus probe (CAC)5 yielded two aberrant bands for the proband, i.e. bands exhibited by neither parent. This finding resulted in a comparatively low paternity probability of 0.02934 which is suggestive of, but does not unequivocally prove, false paternity. Subsequent analysis with other multi- and single-locus systems, however, failed to confirm this preliminary result. The paternity probability computed on the basis of the single-locus systems was 0.99997, providing compelling evidence in favour of true paternity. The present case thus demonstrates that even when two mutations turn up in a DNA fingerprint, these may be readily recognized as such.

Abortion, Spontaneous↗
PubMed1993

Allele frequencies and linkage disequilibrium of polymorphic DNA markers of the Huntington disease region in the German population.

Allele frequencies of 14 different restriction fragment length polymorphisms from 12 DNA markers within the Huntington disease (HD) region were evaluated in the German population. No significant differences from published data of allele frequencies from chromosomes of Caucasian ancestry were found. The analysis of eight DNA polymorphisms in 87 HD families of German origin revealed significant non-random association with the HD locus and the D4S95 locus (p674/AccI/MboI), a result that is consistent with all other published studies. These results are confirmed by the fact that the HD gene maps to this region.

Alleles↗
PubMed1993

Mitotic stability and meiotic variability of the (CAG)n repeat in the Huntington disease gene.

The gene causing Huntington's disease, an autosomal dominantly inherited, neurodegenerative disorder, has been identified recently. The corresponding mutation is involving an expansion in the number of (CAG)n repeats in the coding region of the Huntington's disease gene on chromosome 4. In this report, we demonstrate the length variation of the repeat in 513 non-HD chromosomes from normal individuals and HD patients showing 23 alleles with 11 to 33 repeats. Analyzing the inheritance of the (CAG)n stretch we found meiotic instability for HD alleles ([CAG]40 to [CAG]75) with a mutation frequency of approximately 0.7, while in 431 meioses of normal alleles only two expansions were identified. The risk of expansion during spermatogenesis is enhanced compared to oogenesis explaining juvenile onset by transmission from affected fathers. Further, the number of (CAG)n copies in an affected individual in relation to the sex of the transmitting parent was evaluated and no significant differences were found. No mosaicism or differences in the repeat lengths were observed in the DNA from different tissues including brain and lymphocytes of two HD patients indicating mitotic stability of the mutation. Therefore, the determination of the repeat number in the DNA of blood lymphocytes is probably representative of all tissues in a patient.

Alleles↗
PubMed1993

Attitudes of neurologists, psychiatrists, and psychotherapists towards predictive testing for Huntington's disease in Germany.

Predictive testing for Huntington's disease (HD) in Germany is performed by genetic counsellors, neurologists, psychiatrists, and psychotherapists. In order to evaluate the attitudes of neurologists, psychiatrists, and psychotherapists in Germany towards predictive testing for HD, a postal questionnaire was sent to this group. Two German Bundesländer were chosen, Baden Württemberg (BW) and Niedersachsen (NS). Of 469 persons interviewed the response rate was 32.6%. The questionnaire consisted of 17 items assessing sociodemographic data, acquaintance with HD patients, lay organisations, attitudes towards genetic counselling, presymptomatic and prenatal DNA testing, and reproduction of persons at risk for HD. More than 70% of the subjects were well informed about predictive DNA testing but knowledge about the details of the test procedure, especially the World Federation of Neurology (WFN) and International Huntington Association (IHA)1 recommendations, was quite low (11.8%). Nevertheless, the majority would recommend predictive testing for HD although they anticipated problems for the probands. The majority of our respondents favoured psychological test and post-test counselling for those tested. Concerning reproduction, most subjects favoured prenatal testing or that persons at risk should refrain from having children. We found that the opinions of practitioners and at risk persons differed with respect to the predictive DNA test and, particularly, to prenatal testing. Therefore the testing procedure could be improved if practitioners were better informed about the DNA test in general and about the attitudes and wishes of their patients.

Attitude of Health Personnel↗
PubMed1992

Prenatal diagnosis of Huntington's disease (HD): experiences with six cases and PCR.

In the course of a 2-year predictive testing programme for Huntington's disease (HD), six couples from a total of 52 applicants requested prenatal testing. In each case, the pregnancy was in the first or second trimester when the couples were referred for DNA diagnosis. In five cases, exclusion testing was offered; in one case, a person at risk with an increased risk of being a gene carrier requested prenatal diagnosis. In all cases, informative markers for prenatal testing could be determined. Whenever possible, the newer technique of polymerase chain reaction (PCR) for D4S125 was applied to perform rapid prenatal diagnosis. Two couples withdrew before chorionic villus sampling was undertaken; prenatal diagnosis was completed in the remaining four cases. After exclusion testing, two pregnancies were determined to have an increased risk and two fetuses to have a low risk of being HD gene carriers.

Blotting, Southern↗
PubMed1992

Clinical, cytogenetic and molecular investigations in three patients with Wolf-Hirschhorn syndrome.

Clinical, cytogenetic and molecular studies were performed in three patients with Wolf-Hirschhorn syndrome (WHS). In all cases the altered chromosome 4 appeared to be the result of a de novo deletion. Cytogenetic investigations located the breakpoint at 4p15.3 and 4p13. With cytogenetic methods it was not possible to decide whether these deletions were terminal or interstitial. DNA methods also failed to define a distal breakpoint within the 4p16.3 region which might have indicated an interstitial deletion. According to the literature, the paternal chromosome 4 is preferentially deleted in most patients with WHS. DNA analysis with polymorphic markers out of the 4p16.3 region revealed that in two of the cases reported here the deleted segment was of paternal and in one case of maternal origin.

Abnormalities, Multiple↗