Fragile X chromosome and chromosome condensation

The effect of chromosome condensation on the frequency of expression of the fragile X chromosome was examined. Chromosome decondensation substances were tested for their ability to elicit expression or improve frequencies of expression of the fragile X chromosome in five patients. The substances tested included the AT specific DNA ligands ethidium bromide, Hoechst 33258, and netropsin, and the GC specific substances actinomycin D and olivomycin. Under culture conditions appropriate for eliciting fragile X expression none of the decondensation compounds studied significantly altered frequencies of expression, nor did any of the substances elicit fragile X expression under conditions that normally suppress fragile X expression. The fragile X was found to be more frequently evident in less condensed chromosome preparations from fibroblasts. The implications of these findings with respect to the nature of fragile sites are discussed.     

Methylation and the X chromosome

Recent approaches towards an understanding of the molecular basis of X-chromosome inactivation in mammals suggest that regulation is due to multiple events including DNA methylation.     

Surnames and the Y chromosome

A randomly ascertained sample of males with the surname "Sykes" was typed with four Y-chromosome microsatellites. Almost half the sample shared the same Y-chromosome haplotype, which has not been observed in control samples either from the same geographic region or from the United Kingdom as a whole. This points to a single surname founder for extant Sykes males, even though written sources had predicted multiple origins. The distribution of other Sykes Y-chromosome haplotypes were not significantly different from those in controls and may be accounted for by the historical accumulation of nonpaternity during the past 700 years, in which case the average rate estimate is 1.3%/generation. If this pattern is reproduced with other surnames, it may have important forensic and genealogical applications.     

Large-scale mapping and chromosome jumping in the q27 region of the human X chromosome

We have used pulsed field gel electrophoresis for further physical mapping studies in the q27 region of the human X chromosome. We show that the DXS 102 locus and the F9 gene are separated by only 300 kb despite a genetic distance of 1.4 cM; this linkage orients our large-scale map and shows that the mcf.2 transforming sequence is telomeric to F9. A BssHII complete-digest jumping library was used to jump toward the DXS 105 locus; a 130-kb jump was achieved and the corresponding "linking clone" was obtained.     

Y chromosome replication and chromosome arrangement in germ line cells and sperm of the rat

The chronology of Y chromosome replication in meiosis of male adult rats was investigated. ³HTdR was injected into the testes and animals were sacrificed at 2-hour intervals from 2 to 24 hour after the injection; and at 2-day intervals from 2 to 64 days after the injection. Autoradiograms from germ line cell spreads were prepared. The study of spermatogonial metaphases showed that the Y chromosome is the last to begin and end DNA synthesis. Consequently, by detecting such a pattern of replication it was possible to trace the asynchronous Y from spermatogonia to sperm. Assuming that Y chromosomes are early replicating in preimplantation embryos of mammals it is proposed that Y chromosome of rats shift from late to early replicating in the first divisions of the fertilized egg. Moreover, the analysis of the patterns of sperm labeling allow one to infer that chromosomes are end-to-end associated in sperm nuclei, and that the Y chromosome and perhaps autosomes as well occupy a constant position in sperm of rats.     

Oncogenes and the mammalian X chromosome

Summary None of the up to now localized and expressed oncogenes maps to the mammalian X chromosome. This fact is discussed in the light of a trans-acting regulation mechanism for oncogenes. Such a specific regulation mechanism is demonstrated here for a qualitative change — i.e., varying timing of DNA-replication — at the putative c-myc gene locus in band 15E of murine T-cell leukemia. In intraspecific hybrids between tumor and non-tumor cells this qualitative change spreads over to all chromosomes 15 of the same cell, irrespective of their origin. This effects is thought to reflect a binary trans-acting regulation mechanism between homologous chromosomal loci. In the past specific chromosomal aberrations have been described in various tumors but none of these aberrations involve the X chromosome. For the mammalian X chromosome where there is usually only one gene copy per cell active the described kind of binary trans-acting regulation between homologous gene loci is rendered impossible.     

Reciprocal translocation and the Philadelphia chromosome

Summary We examined metaphases from three patients with chronic myeloid leukaemia and a typical Philadelphia chromosome with one chromosome 9 as the recipient to determine whether the 9q+ 22q- translocation is reciprocal. Good quality G-banded photographs of the chromosomes concerned were subjected to light absorption density analysis. This provided enlarged tracings corresponding to the relevant chromosome regions and so facilitated accurate measurement. This technique has unambiguously shown that the typical Philadelphia chromosome results from a reciprocal translocation and that probably no material is gained or lost in the exchange. Furthermore, in a total of six patients for whom sequential G and C banding was performed, the chromosome 9 with the largest block of centromeric heterochromatin received the translocated material. We offer tentative explanations for this curious observation.     

Sex chromosome homologies between human and fish revealed by the chromosome painting method

Human sex chromosome-specific probes were hybridized to metaphase spreads of three fish species, Monopterus albus Zuiew, Danio rerio and Mastacembelus aculeatus Basilewsky, to reveal evolutionary conservation of sex chromosomal segments between distantly related species of vertebrates. The human X chromosomal paint disclosed 4, 8, and 6 conserved syntenic segments in the karyotypes of the three fish species respectively, which were scattered in several pairs of homologous chromosomes. But no conserved segment was identified in our experiments when the human Y chromosomal probes were used. The evolution of the X chromosome of vertebrates is discussed.     

Is the Y chromosome of Drosophila an evolved supernumerary chromosome?

The Y chromosomes of most Drosophila species are necessary for male fertility but they are not involved in sex determination. They have many puzzling properties that resemble the effects caused by B chromosomes. Classical genetic and molecular studies reveal substantial affinities between Y and B chromosomes and suggest that the Y chromosomes of Drosophila are not degenerated homologues of the X chromosomes, but rather that their Y chromosomes evolved as specialized supernumeraries similar to classical B chromosomes.     

Origin recognition and the chromosome cycle

Prior to the initiation of DNA replication, chromosomes must establish a biochemical mark that permits the recruitment in S phase of the DNA replication machinery that copies DNA. The process of chromosome replication in eukaryotes also must be coordinated with segregation of the duplicated chromosomes to daughter cells during mitosis. Protein complexes that utilize ATP coordinate events at origins of DNA replication and later they participate in the initiation of DNA replication. In eukaryotes, some of these proteins also play a part in later processes that ensure accurate inheritance of chromosomes in mitosis, including spindle attachment of chromosomes, accurate duplication of centrosomes and cytokinesis. A perspective of how ATP-dependent proteins accomplish this task in eukaryotes is discussed.     

Human evolution and the Y chromosome

The past two years have seen the increased study of Y-chromosome polymorphisms and their relationship to human evolution and variation. Low Y-chromosome sequence diversity indicates that the common ancestor of all extant Y chromosomes lived relatively recently and the consensus of estimates of time to the most recent common ancestor concur with estimates of the mitochondrial DNA ancestor; but we do not know where this ‘Adam’ lived. Though the reason for low nucleotide diversity on the Y-chromosome remains unresolved, some of the mutations are proving highly informative in tracing human prehistoric migrations and are generating new hypotheses on human colonizations and migrations. The recent discovery of highly polymorphic microsatellites on the Y offers new possibilities for the investigation of more recent human evolutionary events, including the identification of male founders.