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C R Müller

Publications and source records attributed to C R Müller.

At least 91 records · Page 5Linked to original sources
PubMed1989

Hot spot of recombination within DXS164 in the Duchenne muscular dystrophy gene.

The DMD gene, which spans more than 2,000 kbp, has been assigned to band Xp21 of the X chromosome. Two subclones (PERT 87-1 and PERT 87-15) of the intragenic locus DXS164 physically are separated by approximately 60 kbp. Linkage studies were done in 49 informative DMD families by using the LINKAGE program. Crossing-over between the loci studied occurred in four families. A recombination rate of 4% (support interval [Zmax-1] 1%-10%), which was 54 (support interval 14-135-fold) times higher than expected, was found with a maximum lod score of 13.50. These data suggest a hot spot for recombination within DXS164.

Alleles↗
PubMed1986

Estimation of the male to female ratio of mutation rates from the segregation of X-chromosomal DNA haplotypes in Duchenne muscular dystrophy families.

A novel procedure is presented to estimate the ratio of male to female mutation rates for Duchenne muscular dystrophy (DMD). X-specific restriction fragment length polymorphisms are used to establish DNA haplotypes in three-generation DMD families. From the proportion of DMD patients who have inherited their maternal grandfather's X chromosome, the ratio of mutation rates can be calculated. In contrast to classical methods, the proposed procedure is not restricted to sporadic or familiar cases nor is any information on the carrier status of female relatives required.

DNA↗
PubMed1986

DNA finger printing by oligonucleotide probes specific for simple repeats.

Interspersed simple repetitive DNA is a convenient genetic marker for analysis of restriction fragment length polymorphisms (RFLPs) because of the numbers and the frequencies of its alleles. Oligonucleotide probes specific for variations of the GATCA simple repeats have been designed and hybridized to a panel of human DNAs digested with various restriction enzymes. Numerous RFLPs were demonstrated in AluI and MboI digested DNA with "pure" GATA oligonucleotides as probes. The optimal length of the probe for RFLP analysis was 20 bases taking into account fragment lengths (1.5-7 kilobases = kb), signal to background ratio, and number of clearly evaluable RFLPs. By using different restriction enzymes individual-specific hybridization patterns ("DNA fingerprints") can be established. Hypervariable simple repeat fragments are stably inherited in a Mendelian fashion. Advantages of this method are discussed.

DNA↗
PubMed1986

Rapid sexing of native amniotic cells by hybridization to a cloned Y chromosome DNA probe.

A cloned DNA fragment from a Y chromosome genomic library was used for prenatal sex determination. Native cells from as little as 0.5 ml of amniotic fluid were analyzed by a dot blot hybridization technique without prior cell culture. Identification of male fetuses was possible within 3 days and confirmed by subsequent conventional karyotyping. This method of rapid sex screening is an alternative to the other methods of prenatal determination to the conventional chromosome analysis because it is a more rapid method, and to the karyotyping of chorion biopsy material because amniocentesis seems to have a lower risk and can still be performed when chorion biopsy is not more possible.

Amniotic Fluid↗
PubMed1984

Preparative dual-beam sorting of the human Y chromosome and in situ hybridization of cloned DNA probes.

Bivariate Hoechst/chromomycin flow karyotypes for chromosomes from a Chinese hamster-human hybrid cell line (CH-Y-VII) were established that have retained a human Y chromosome. These bivariate flow karyotypes showed the human Y chromosome to be completely separated from the peaks for the Chinese hamster chromosomes. In preparative dual-beam sorting experiments, 3 X 10(6) chromosomes were sorted from the Y peak into frozen petri dishes. An examination of Q-banded samples of sorted chromosomes revealed that 82% +/- 5% of them were human Y chromosomes. The DNA from the sorted chromosomes (approximately 250 ng) was isolated and used to establish a genomic library (vector lambda gt WES. lambda B). Three clones (YACG 45, 52, 54) of this library containing inserts of repetitive human DNA were used for chromosomal localization by means of in situ hybridization to metaphase spreads of male human lymphocytes and of CH-Y-VII cells. In all three cases, a significant binding to the human Y chromosome was observed. A more detailed study of the chromosomal distribution of sequences homologous to the insert of YACG 45 suggested the existence of minor binding sites on several human autosomes. Southern blot analysis revealed the existence of other human specific sequences without Y chromosome specificity.

Animals↗
PubMed1984

Sex chromosome positions in human interphase nuclei as studied by in situ hybridization with chromosome specific DNA probes.

Two cloned repetitive DNA probes, pXBR and CY1, which bind preferentially to specific regions of the human X and Y chromosome, respectively, were used to study the distribution of the sex chromosomes in human lymphocyte nuclei by in situ hybridization experiments. Our data indicate a large variability of the distances between the sex chromosomes in male and female interphase nuclei. However, the mean distance observed between the X and Y chromosome was significantly smaller than the mean distance observed between the two X-chromosomes. The distribution of distances determined experimentally is compared with three model distributions of distances, and the question of a non-random distribution of sex chromosomes is discussed. Mathematical details of these model distributions are provided in an Appendix to this paper. In the case of a human translocation chromosome (Xqter----Xp22.2::Yq11----Yqter) contained in the Chinese hamster X human hybrid cell line 445 X 393, the binding sites of pXBR and CY1 were found close to each other in most interphase nuclei. These data demonstrate the potential use of chromosome-specific repetitive DNA probes to study the problem of interphase chromosome topography.

Cell Nucleus↗
PubMed1983

Sex chromosome-specific DNA sequences.

Genetic linkage analysis using restriction fragment length polymorphisms is feasible for a human sex-linked disorder even when the primary gene product is not known. Distant probes localise a defect, while more closely linked clones can be used either for unambiguous carrier detection, particularly if sequences on both sides of the gene defect can be isolated, or for prenatal diagnosis using DNA obtained in early pregnancy by trophoblast sampling. Furthermore, with the isolation of sex chromosome libraries and the development of molecular biological techniques, a greater understanding of the basis of gonadal differentiation and sex-linked diseases should be achieved in the next few years.

Base Sequence↗
PubMed1983

Cloning of genomic sequences from the human Y chromosome after purification by dual beam flow sorting.

Human Y chromosomes were purified by dual beam flow sorting from a human X Chinese hamster cell line retaining the Y as the only free human chromosome. DNA was extracted from the Y fraction and cloned into lambda gtWES . lambda B vector arms. More than 100 recombinant clones carrying human inserts have been characterised by Benton-Davis plaque screening and Southern blotting or in situ hybridisation. Several repetitive sequences were found to be predominantly located on the Y, whereas the majority also cross-hybridised with autosomal DNA. One repetitive clone gave a specific hybridisation signal with the X and the Y chromosome but not with autosomes. Preliminary evidence indicates that many clones contain single copy as well as repetitive sequences. However, no Y-specific single copy sequence has yet been identified.

Animals↗
PubMed1983

An XX male with a single STS gene dose.

There is substantial evidence that many XX males arise from an X/Y interchange, so that a terminal Xp segment carrying the Xg locus, but not the neighboring steroid sulfatase (STS) locus, is replaced by part of the Y chromosome. We show here that one of the two X chromosomes of an XX male with low intracellular levels of STS does not express the STS gene.

Animals↗
PubMed1982

Recombined flanks of the variable and joining segments of immunoglobulin genes.

The mechanism of generating immunoglobulin light chain genes by rearrangement of variable (V), joining (J), and constant (C) gene segments is still unknown. It has been discussed mostly in terms of excision and deletion of the DNA between the recombined V and J gene segments. However, the finding of DNA digests from the mouse myeloma T of a fragment (called f-T) that contains the 3' flank of a V kappa and the 5' flank of a J1 gene segment argued against a simple deletion mechanism [Steinmetz, M., Altenburger, W. & Zachau, H. G. (1980) Nucleic Acids Res. 8, 1709--1720]. The origin of fragment f-T has now been investigated by cloning and determining the sequence of the germ-line V gene segment that apparently participated in its formation. Moreover, analogous fragments containing flanking sequences were isolated from the myelomas MOPC 173 and 41 (f-173 and f-41) and studied by sequence analysis. The f fragments appear to be recombination products of V--J rearrangements reciprocal to rearranged kappa genes but, at least in the cases of f-T and f-173, not of the rearranged V genes present in the same tumor cell. This fact is best explained by a sister chromatid exchange mechanism of V--J recombination because, by this model, the rearranged V genes and the reciprocal flank recombination products would segregate into different cells during the following mitosis. The possibility is suggested that there exists in lymphocyte differentiation more than one mechanism of V--J recombination.

Animals↗
PubMed1981

X-linked recessive ichthyosis in three sisters: evidence for homozygosity.

A family with ichthyosis, severely affecting both men and women, is reported. The clinical, histological and genetic data are strongly suggestive of X-linked recessive ichthyosis. Assay of steroid sulphatase in cultured skin fibroblasts from two ichthyotic female patients revealed an absence of this enzyme and thus confirmed this diagnosis. To our knowledge, this is the first report of proven X-linked recessive ichthyosis in women.

Adult↗
PubMed1980

Regional assignment of the gene locus for steroid sulfatase.

The gene locus for steroid sulfatase, deficiency of which causes X-linked ichthyosis, is assigned to Xp11 leads to Xpter by analysis of 24 man-Chinese hamster somatic cell hybrids. High steroid sulfatase activity in a hybrid clone having retained only part of Xq is explained by demonstration of an additional late-replicating human X chromosome. This observation confirms previous evidence for noninactivation of the STS locus.

Animals↗
PubMed1980

Assignment by deletion mapping of the steroid sulfatase X-linked ichthyosis locus to Xp223.

A male child and his mother who are nullisomic and monosomic, respectively, for the distal portion of Xp because of an unbalanced X-Y translocation were tested for steroid sulfatase activity after clinical examination had yielded evidence for ichthyosis in the boy. Deficiency of steroid sulfatase was found in the male patient, while in his mother enzyme levels were in the heterozygous range. These results, based on cytogenetic evidence obtained with an elongation technique, indicate that the STS locus is at Xp 223.

Adult↗