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B Dittrich

Publications and source records attributed to B Dittrich.

At least 37 records · Page 2Linked to original sources
PubMed1997

Imprinted segments in the human genome: different DNA methylation patterns in the Prader-Willi/Angelman syndrome region as determined by the genomic sequencing method.

A deletion of 15q11-q13 and uniparental disomy 15 lead to Prader-Labhart-Willi syndrome (PWS) or Angelman syndrome (AS) because this region contains genes expressed exclusively from the paternal (PWS) or maternal (AS) chromosome, respectively. DNA methylation plays a role in the control of imprinted gene expression, but so far only a few 5'-CG-3' dinucleotides within the recognition sites of the methylation sensitive enzymes have been studied. As part of a study on DNA methylation patterns in the human genome, we have applied the bisulfite protocol of genomic sequencing to study all 5'-CG-3' dinucleotides around exon 1 of SNRPN and at the D15S63 locus, which contains a start site for alternative SNRPN transcripts possibly involved in imprint switching during gametogenesis. At least 17 PCR products derived from single chromosomes of normal individuals as well as PWS and AS patients have been sequenced. We have found that cytosine residues outside 5'-CG-3' dinucleotides are always unmethylated. However, > 96% of all of the 23 5'-CG-3' dinucleotides around SNRPN exon 1 are methylated on the maternal chromosome and completely devoid of methylation on the paternal chromosome. This finding is in contrast to the D15S63 locus, where only the two Cfol/Hhal sites are methylated on the maternal chromosome at the same frequency as seen for the SNRPN segment. At the other five 5'-CG-3' dinucleotides, differential methylation is less pronounced, i.e. 45-70% on the maternal chromosome and 5-14% on the paternal chromosome. The differences between SNRPN and D15S63 methylation may reflect different biological functions of the alternative SNRPN transcripts. The systematic investigation of 5'-CG-3' methylation patterns as reported here will provide the basis for a PCR-based methylation test to diagnose PWS and AS.

5-Methylcytosine↗
PubMed1996

Imprint switching on human chromosome 15 may involve alternative transcripts of the SNRPN gene.

Imprinting on human chromosome 15 is regulated by an imprinting centre, which has been mapped to a 100-kb region including exon 1 of SNRPN. From this region we have identified novel transcripts, which represent alternative transcripts of the SNRPN gene. The novel exons lack protein coding potential and are expressed from the paternal chromosome only. We have also identified intragenic deletions and a point mutation in patients who have Angelman or Prader-Willi syndrome due to a parental imprint switch failure. This suggests that imprint switching on human chromosome 15 may involve alternative SNRPN transcripts.

Alternative Splicing↗
PubMed1995

Inherited microdeletions in the Angelman and Prader-Willi syndromes define an imprinting centre on human chromosome 15.

A subset of patients with Angelman and Prader-Willi syndrome have apparently normal chromosomes of biparental origin, but abnormal DNA methylation at several loci within chromosome 15q11-13, and probably have a defect in imprinting. Using probes from a newly established 160-kb contig including D15S63 (PW71) and SNRPN, we have identified inherited microdeletions in two AS families and three PWS families. The deletions probably affect a single genetic element that we term the 15q11-13 imprinting centre (IC). In our model, the IC regulates the chromatin structure, DNA methylation and gene expression in cis throughout 15q11-13. Mutations of the imprinting centre can be transmitted silently through the germline of one sex, but appear to block the resetting of the imprint in the germline of the opposite sex.

Angelman Syndrome↗
PubMed1994

Detection of aberrant DNA methylation in unique Prader-Willi syndrome patients and its diagnostic implications.

Most patients with Prader-Willi syndrome have a deletion of 15q11-13 or maternal uniparental disomy for chromosome 15. The shortest region of deletion overlap is presently defined by the gene for the small nuclear ribonucleoprotein N (SNRPN). We have investigated the integrity of SNRPN as well as the methylation status of D15S63 (PW71) in two patients with apparently normal chromosomes 15 of biparental origin. SNRPN is normal in one patient and deleted in the other one. Both patients are intact at the D15S63 locus, but have an abnormal methylation pattern. These results suggest that a DNA sequence close to SNRPN determines the methylation status of D15S63 and that the methylation test does not only detect the common deletions and uniparental disomy, but other rare lesions as well.

Adolescent↗
PubMed1994

Imprinting mutations suggested by abnormal DNA methylation patterns in familial Angelman and Prader-Willi syndromes.

The D15S9 and D15S63 loci in the Prader-Willi/Angelman syndrome region on chromosome 15 are subject to parent-of-origin-specific DNA methylation. We have found two Prader-Willi syndrome families in which the patients carry a maternal methylation imprint on the paternal chromosome. In one of these families, the patients have a small deletion encompassing the gene for the small nuclear ribonucleoprotein polypeptide N, which maps 130 kb telomeric to D15S63. Furthermore, we have identified a pair of nondeletion Angelman syndrome sibs and two isolated Angelman syndrome patients who carry a paternal methylation imprint on the maternal chromosome. These Angelman and Prader-Willi syndrome patients may have a defect in the imprinting process in 15q11-13. We propose a model in which a cis-acting mutation prevents the resetting of the imprinting signal in the germ line and thus disturbs the expression of imprinted genes in this region.

Angelman Syndrome↗
PubMed1993

Characterization of a DNA sequence family in the Prader-Willi/Angelman syndrome chromosome region in 15q11-q13.

IR4-3R (D15S11) is an anonymous DNA sequence from human chromosome 15. Using YAC cloning and restriction enzyme analysis, we have found that IR4-3R detects five related DNA sequences, which are spread over 700 kb within the Prader-Willi/Angelman syndrome chromosome region in 15q11-q13. The RsaI and StyI polymorphisms, which were described previously, are associated with the most proximal copy of IR4-3R and are in strong linkage disequilibrium. IR4-3R represents the third DNA sequence family that has been identified in 15q11-q13.

Alleles↗
PubMed1993

Molecular definition of the Prader-Willi syndrome chromosome region and orientation of the SNRPN gene.

The Prader-Willi syndrome and the Angelman syndrome are caused by the loss of function of distinct but closely linked genes on human chromosome 15. Based on a yeast artificial chromosome restriction map and two key patients we have determined that the shortest region of deletion overlap in the Prader-Willi syndrome comprises 320 kb. The region includes the anonymous DNA marker PW71 (D15S63) and the gene for the small nuclear ribonucleoprotein N (SNRPN). The SNRPN gene maps 130 kb distal to PW71 and is transcribed from centromere to telomere.

Autoantigens↗
PubMed1993

Characterization of a methylation imprint in the Prader-Willi syndrome chromosome region.

In adult human tissues, a HpaII and a CfoI restriction site at the PW71 (D15S63) locus in the Prader-Willi syndrome region on chromosome 15 are methylated on the maternal chromosome, but unmethylated on the paternal chromosome. The HpaII site is part of a sequence with high homology to the long terminal repeat of human endogenous retroviruses. Another HpaII site at the PW71 locus is methylated on both chromosomes. Sperm DNA carries the adult paternal methylation pattern. Oocyte DNA could not be studied. In chorion, placenta and tumor DNA, both HpaII sites are unmethylated. These findings suggest that the PW71 methylation imprint is established in the germline and that extraembryonic tissues and tumors are hypomethylated.

Adult↗
PubMed1992

Molecular diagnosis of the Prader-Willi and Angelman syndromes by detection of parent-of-origin specific DNA methylation in 15q11-13.

The Prader-Willi syndrome (PWS) and the Angelman syndrome (AS) are distinct genetic disorders that are caused by a deletion of chromosome region 15q11-13 or by uniparental disomy for chromosome 15. Whereas PWS results from the absence of a paternal copy of 15q11-13, the absence of a maternal copy of 15q11-13 leads to AS. We have found that an MspI/HpaII restriction site at the D15S63 locus in 15q11-13 is methylated on the maternally derived chromosome, but unmethylated on the paternally derived chromosome. Based on this difference, we have devised a rapid diagnostic test for patients suspected of having PWS and AS.

Adult↗
PubMed1992

Molecular dissection of the Prader-Willi/Angelman syndrome region (15q11-13) by YAC cloning and FISH analysis.

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct mental retardation disorders associated with deletions of proximal 15q (q11-q13) of different parental origin. Yeast artificial chromosome (YAC) clones were isolated for 9 previously mapped DNA probes from this region, and for one newly derived marker, LS6-1 (D15S113). A YAC contig of 1-1.5 Mb encompassing four markers (ML34, IR4-3R, PW71, and TD189-1) was constructed. Multi-color fluorescence in situ hybridization (FISH) analysis of interphase nuclei was combined with YAC contig information to provide the following order of markers: cen-IR39-ML34-IR4-3R-PW71-TD189-1-LS6++ +-1-TD3-21-GABRB3-IR10-1-CMW1-tel. FISH analysis was performed on 8 cases of PWS and 3 cases of AS, including 5 patients with normal karyotypes. All eleven patients were deleted for YACs in the interval from IR4-3R to GABRB3. On the proximal side of the deletion interval, 10/10 breakpoints fell within a single ML34 YAC of 370 kb. On the distal side, 8/9 breakpoints fell within a single IR10-1 YAC of 200 kb. These results indicate a striking consistency in the location of the proximal and distal breakpoints in PWS and AS patients. FISH analysis on a previously reported case of familial AS confirmed a submicroscopic deletion including YACs corresponding to LS6-1, TD3-21 and GABRB3 and supports the separation of the PWS and AS critical regions. Since these three YACs do not overlap each other, the minimum size of the AS critical region is > or = 650 kb.

Angelman Syndrome↗
PubMed1991

Predictive QSAR models for estimating ecotoxic hazard of plant-protecting agents: target and non-target toxicity.

Quantitative structure-activity relationships (QSARs) are evaluated for predicting pesticides' effects on non-target and target organisms: aquatic biota, mammals, soil micro-organisms, and plants. Satisfactory estimates of pesticides' fish toxicity are obtained from log POW-dependent QSARs derived using chemicals of similar polarity and reactivity. Algal toxicity of herbicidal compounds reflects interactions with the electron transport chain in photosystem II and can be modelled by QSARs describing the Hill reaction inhibition. The ranking in effects on soil micro-organisms is evaluated from models derived using in-vitro bacteria systems. Mammalian toxicity can be estimated by QSARs using the partition coefficient log POW and electronic terms derived by MNDO quantum mechanical calculations. In general, the targets are more susceptible than the non-target species towards phenylurea herbicides. Plants and algae constitute the most sensitive populations, corresponding to the same mode of action. Differences in mode of action towards bacteria, rats, and fish, which are similarly sensitive organisms, are revealed by QSAR analyses.

Animals↗
PubMed1976

Analysis of antibody populations to oligo-D-alanine. VIII. Sequential studies on properties of antibody subpopulations: rate constant, affinity, and isoelectric focusing spectrum.

Allotypically marked antisera to the hapten oligo-D-alanine were studied over periods up to 10 months in individual mice and in serial transfers of both nonimmune and memory cells to irradiated recipients. Parameters observed were divalent association rate constants, affinity and autoradiography of isoelectric focusing (IEF) spectra. The two allotypic subpopulations of heterozygous mice are shown to be independent with respect to affinity. Association rate constant, affinity, and IEF spectra of the antibody populations remain largely stable in most mice over prolonged periods. There is an occasional isolated dramatic change in a single property of one allotypic subpopulation; this may be in the direction of either lower or higher rate constant or affinity. While different recipients of naive spleen cells from a single donor, when immunized, differ one from the other in the measured antibody properties, the characteristics now established in each recipient persist in a lineage of transferred memory cells up to 4 generations, with infrequent changes in isolated properties of only one allotypic subpopulation. The limited changes observed would be in agreement with a model of moderate somatic variability superimposed on a small spectrum of germ line genes.

Alanine↗
PubMed1976

[Haptoglobin in domestic mammals. V. Plasma haptoglobin level in cattle under pathological conditions].

The haptoglobine concentration in the blood plasma of cattle tends to rise to more than 10 mg/100 ml in the presence of acute inflammation anywhere in the organism. They were 40 mg/100 ml and above in the presence of traumatic reticuloperitonitis. The absence of haptoglobin multiplication in the plasma is a high-probability indicator to the absence of that inflammatory process. chronic inflammation will only in exceptional cases entail plasma-haptoglobin multiplication. Concentrations will not be pathologically increased in cattle with positive reaction to haematological testing for leucosis.

Actinobacillosis↗
PubMed1975

[Mineral content of various tissues in cattle. 4. Studies on dry matter, Ca, Mg, Na and K concentration in mucous membrane and muscle layer of various bovine gastrointestinal sections].

Samples of the following parts of the gastrointestinal tract were collected from 20 slaughter cattle: - oesophagus, reticulum, omasum, rumen, abomasum, duodenum, jejunum, ileum, colon (beginning and end). There were considerable differences in mineral content, related to the differing functions of each part. Forestomach mucosa contained high concentrations of Ca and Mg, attributable to accumulation and separation of mineral salts. In the three segments of small intestine there was generally more Mg than Ca, with high concentrations of Na and K. The tabulated results are intended to provide a basis for comparison with pathological states.

Animals↗