Highest Gene Concentration Research Articles

Molecular cytogenetic analysis of telomere rearrangements.

Genomic imbalances involving the telomeric regions of human chromosomes, which contain the highest gene concentration in the genome, are proposed to have severe phenotypic consequences. For this reason, it is important to identify telomere rearrangements and assess their contribution to human pathology. This unit describes the structure and function of human telomeres and outlines several methodologies that can be employed to study these unique regions of human chromosomes. It is a revision of the original version of the unit published in 2000, now including an introductory section describing advances in the discipline that have taken place since the original publication.

Molecular Cytogenetic Analysis of Telomere Rearrangements

Genomic imbalances involving the telomeric regions of human chromosomes, which contain the highest gene concentration in the genome, are proposed to have severe phenotypic consequences. For this reason, it is important to identify telomere rearrangements and assess their contribution to human pathology. This unit describes the structure and function of human telomeres and outlines several FISH-based methodologies that can be employed to study these unique regions of human chromosomes.

Dinucleotide repeat polymorphism at the human chromosome 11p telomere (D11S2071)

The recent publication of detailed PCR-based linkage maps for all human chromosomes (3, 5, 9) as greatly facilitated linkage mapping of disease genes. However, most of the markers on these maps have been isolated using approaches based on random screening of genomic libraries. As a consequence, the completeness of coverage of the map in the telomeric chromosomal regions is uncertain. To remove this uncertainty and to aid in positional cloning of disease genes in telomeric regions, it is necessary to develop polymorphic markers that are physically linked to the telomeres of all chromosomes. The need for telomeric markers is highlighted by the discovery that the highest gene concentrations in the human genome are in subtelomeric regions. 12 refs., 1 tab.

The isochore patterns of mammalian genomes and their phylogenetic implications

The compositional distributions of high molecular weight DNA fragments from 20 species belonging to 9 out of the 17 eutherian orders were investigated by analytical CsCl density gradient centrifugation and by preparative fractionation in Cs2SO4/BAMD density gradients followed by analysis of the fractions in CsCl. These compositional distributions reflect those of the isochores making up the corresponding genomes. A "general distribution" was found in species belonging to eight mammalian orders. A "myomorph distribution" was found in Myomorpha, but not in the other rodent infraorders Sciuromorpha and Histricomorpha, which share the general distribution. Two other distributions were found in a megachiropteran (but not in microchiropteran, which, again, shares the general distribution) and in pangolin (a species from the only genus of the order Pholidota), respectively. The main difference between the general distribution and all other distributions is that the former contains sizable amounts (6-10%) of GC-rich isochores (detected as DNA fragments equal to, or higher than, 1.710 g/cm3 in modal buoyant density), which are scarce, or absent, in the other distributions. This difference is remarkable because gene concentrations in mammalian genomes are paralleled by GC levels, the highest gene concentrations being present in the GC-richest isochores. The compositional distributions of mammalian genomes reported here shed light on mammalian phylogeny. Indeed, all orders investigated, with the exception of Pholidota, seem to share a common ancestor. The compositional patterns of the megachiropteran and of Myomorpha may be derived from the general pattern or have independent origins.

The highest gene concentrations in the human genome are in telomeric bands of metaphase chromosomes.

Chromosome in situ suppression hybridization has been carried out on human metaphase chromosomes to localize the G+C-richest human DNA fraction (which only represents 3.5% of the genome), as isolated by preparative equilibrium centrifugation in Cs2SO4/3,6-bis(acetatomercurimethyl)-1,4-dioxane density gradient. This fraction essentially corresponds to isochore family H3. The rationale for carrying out this experiment is that this isochore family has, by far, the highest gene concentration, the highest concentration in CpG islands, the highest transcriptional and recombinational activity, and a distinct chromatin structure. The in situ hybridization results obtained show that the H3 isochore family is localized in two coincident sets of bands of human metaphase chromosomes: telomeric bands and chromomycin A3-positive 4',6-diamidino-2-phenylindole-negative bands. This result is the first step toward a complete compositional map of the human karyotype. Because the G+C gradient across isochore families is paralleled by a gene concentration gradient, such a map has structural, functional, and evolutionary relevance.