Biomedical subjects

G A Rappold

Publications and source records attributed to G A Rappold.

62 records · Page 4Linked to original sources

PubMed1984

c-myc and immunoglobulin kappa light chain constant genes are on the 8q+ chromosome of three Burkitt lymphoma lines with t(2;8) translocations.

We have determined the localization of c-myc and the immunoglobulin kappa light chain genes on the 8q+/2p- chromosomes of the three Burkitt lymphoma lines BL21, LY66 and LY91 with t(2;8) translocation by in situ hybridization. BL21 is characterized by a complex translocation in which a piece of chromosome 9 appears to be located between the fragments of chromosome 8 and 2 on the 8q+ chromosome. Our data indicate that in all three cell lines the c-myc gene is located on the 8q+ chromosome proximal to the breakpoint in band 8q24. In all cell lines examined the cluster of kappa variable genes has remained on the 2p- chromosome. In LY91 cells the major part of the joining region remained on 2p-, while the joining region has moved to 8q+ in the cell lines BL21 and LY66. In all three cell lines the constant kappa light chain gene was found on the 8q+ chromosome. The fact that an essentially identical pattern was found in the cell line BL21, with the complex translocation, suggests that the insertion of the piece of chromosome 9 into the 8q+ chromosome might be a secondary event. Our present data fit into the concept that in all Burkitt lymphoma lines investigated so far, including cases with t(8;14) and the variant translocations t(2;8) and t(8;22), the c-myc gene becomes situated at the 5' side of an immunoglobulin constant gene. This may have implications for the generation of somatic mutations in the coding and non-coding part of the c-myc gene.

Burkitt Lymphoma↗

PubMed1984

Chromosome assignment of two cloned DNA probes hybridizing predominantly to human sex chromosomes.

In situ hybridization experiments were carried out with two clones, YACG 35 and 2.8, which had been selected from two genomic libraries strongly enriched for the human Y chromosome. Besides the human Y chromosome, both sequences strongly hybridized to the human X chromosome, with few minor binding sites on autosomes. In particular, on the X chromosome DNA from clone YACG 35 hybridized to the centromeric region and the distal part of the short arm (Xp2.2). On the Y chromosome, the sequence was assigned to one site situated in the border region between Yq1.1 and Yq1.2. DNA from clone 2.8 also hybridized to the centromeric region of the X and the distal part of the short arm (Xp2.2). On the Y, however, two binding sites were observed (Yp1.1 and Yq1.2). The findings indicate that sex chromosomal sequences may be localized in homologous regions (as suggested from meiotic pairing) but also at ectopic sites.

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

Chromosomal localization of a human myosin heavy-chain gene by in situ hybridization.

A cloned rabbit heart muscle myosin heavy-chain cDNA was hybridized in situ with human metaphase chromosomes. The probe was known to have sequence homology with human genomic heavy-chain DNA. Only one site in the human haploid karyotype was labeled with the cDNA, and this site was found on the short arm of chromosome 17. The localization of autoradiographic grains suggests a subregional assignment of the myosin heavy-chain locus to 17p 1,2-pter.

Animals↗

PubMedDate not supplied

A selective difference between human Y-chromosomal DNA haplotypes.

DNA analysis is making a valuable contribution to the understanding of human evolution [1]. Much attention has focused on mitochondrial DNA (mtDNA) [2] and the Y chromosome [3] [4], both of which escape recombination and so provide information on maternal and paternal lineages, respectively. It is often assumed that the polymorphisms observed at loci on mtDNA and the Y chromosome are selectively neutral and, therefore, that existing patterns of molecular variation can be used to deduce the histories of populations in terms of drift, population movements, and cultural practices. The coalescence of the molecular phylogenies of mtDNA and the Y chromosome to recent common ancestors in Africa [5] [6], for example, has been taken to reflect a recent origin of modern human populations in Africa. An alternative explanation, though, could be the recent selective spread of mtDNA and Y chromosome haplotypes from Africa in a population with a more complex history [7]. It is therefore important to establish whether there are selective differences between classes (haplotypes) of mtDNA and Y chromosomes and, if so, whether these differences could have been sufficient to influence the distributions of haplotypes in existing populations. A precedent for this hypothesis has been established for mtDNA in that one mtDNA background increases susceptibility to Leber hereditary optic neuropathy [8]. Although studies of nucleotide diversity in global samples of Y chromosomes have suggested an absence of recent selective sweeps or bottlenecks [9], selection may, in principle, be very important for the Y chromosome because it carries several loci affecting male fertility [10] [11] and as many as 5% of males are infertile [11] [12]. Here, we show that one class of infertile males, PRKX/PRKY translocation XX males, arises predominantly on a particular Y haplotypic background. Selection is, therefore, acting on Y haplotype distributions in the population.

Alleles↗

PubMedDate not supplied

Closely related sequences on human X and Y chromosomes outside the pairing region.

During meiosis the human X and Y chromosomes form a synaptonemal complex which covers most of Yp and the terminal 30% of Xp (ref. 1). By analogy with the autosomes, this is presumed to reflect DNA sequence homology. It has been suggested that these regions of the X and Y chromosomes contain either related or identical loci which are distal to a site of cross-over, and support for these ideas has come from the finding that an X-linked cell-surface antigen controlling gene MIC2 is related to a gene on the Y chromosome. A number of DNA sequences have been shown to occur either on the X and Y chromosomes or on the X, Y and autosomes. We have now isolated a sequence from the Y chromosome which is present on Xq and Yq. This region lies well outside the pairing segments, and sequence analysis reveals no base change in 1 kilobase pair (kb). This high degree of similarity between the X and Y chromosomes near the tips of the long arms is a strong indication that interchange can occur in this region.

Base Sequence↗

PubMedDate not supplied

Hypervariable telomeric sequences from the human sex chromosomes are pseudoautosomal.

Pairing of human X and Y chromosomes during meiosis initiates within the so-called pairing region at the telomeres or the chromosome short arms. Using DNA from the Y chromosome we found sequence homology in the pairing region of the human X and Y chromosomes. This DNA is telomeric, contains repetitive sequences and is highly polymorphic in the population. The polymorphism has allowed family studies which show the sequences are not inherited as though linked to the sex chromosomes. This 'pseudoautosomal' pattern of inheritance points to an obligate recombination in the pairing region of the sex chromosomes during male meiosis.

Chromosome Mapping↗

PubMedDate not supplied

Clinical, cytogenetic and molecular analysis of three 46,XX males.

Cytogenetic analysis, fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR) were applied to characterize the Y-chromosomal breakpoints of three XX male patients. Two of these patients show a breakpoint within a protein kinase gene, PRKY, previously described as a hotspot of ectopic recombination between homologous regions on X and Y chromosomes during male meiosis. The slightly different clinical phenotypes of the three patients cannot be correlated with the localization of the breakpoints.

Adult↗