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[Genetic differentiation of Caucasian wood mice: comparison of isozymic, chromosomal and molecular divergence].

Data on the complex genetic analysis of three sympatric species of Caucasian wood mice, Apodemus ponticus, A. fulvipectus, and A. uralensis are presented. A high degree of genetic differentiation at the isozymic, karyological and molecular (nuclear DNA) levels was revealed. The genetic distances between each pair of species varied significantly within a wide range depending on the analyzed level of the organization of genetic material. Mean values of genetic divergence from one species to another were also variable. These findings indicated that evolution of chromosomes was slower than that of isozymes, and the degree of species divergence was similar on cytogenetic and molecular levels. They also suggested that the rates of species evolution could vary in different phyletic lineages and on different levels of organization. Some phyletic lineages of Apodemus could be distinguished by different directions of evolution.

Animals↗

Dissecting karyotypic patterns in colorectal tumors: two distinct but overlapping pathways in the adenoma-carcinoma transition.

More than 500 colorectal tumors with clonal chromosomal abnormalities have been reported. Although the pattern of aberrations is nonrandom, no specific primary or secondary karyotypic abnormality has been identified. Also, the chronological order in which the aberrations appear during disease progression is not well known. One reason why our understanding of the cytogenetic evolution is unclear is the high degree of karyotypic complexity seen in these tumors. To overcome some of these difficulties we have previously used several statistical methods that allow identification and interpretation of karyotypic pathways as well as establishment of a temporal order of appearance of the imbalances. These methods were applied on 531 colorectal tumor karyotypes. By using a resampling strategy, 1p-, +7, 7q-, and +12p were identified as early events. Two major and two minor cytogenetic pathways were identified by means of principal component analysis. The two major pathways were initiated with 1p- and +7, and the minor pathways were initiated with +12p and 7q-. The +7/+12p tumors were found to be hyperdiploid, whereas those with 1p-/7q- were pseudodiploid. We also show that the adenoma-carcinoma transition in the 1p- pathway is strongly linked to karyoytypic evolution, whereas the +7 pathway is not, and that the cytogenetic pathways are separated at both early and late stages.

Adenoma↗

The karyotype of blastic crisis.

The nonrandomness of chromosome clonal evolution in blastic crisis of chronic myeloid leukemia is well established, with three major changes [+8, +Ph, i(17q)] occurring alone or in combination in over 70% of the patients. The chromosome changes observed in different tissues may reveal the origin of the abnormal clones, as well as provide evidence for distinct or common evolution by different cell populations. The significance of the chromosome abnormalities and their relationship to blastic conversion are discussed. In general, chromosome evolution may be considered a rather reliable predictive or diagnostic parameter of blastic crisis but both the nature and the subsequent behavior of abnormal clones appear to be of critical value. As to the clinical/chromosome correlations, a few major points have emerged: the i(17q) aberration is mostly associated with signs of myeloid differentiation of blasts and a marked basophilia; it is mainly observed in the late stage of the disease, but overall median survival of patients with this marker is usually long; more atypical or complex changes usually are associated with a worse prognosis; patients with only a Ph in their blasts may have a longer survival, at least in some cytologic subgroups; and d) the loss of the Y chromosome seems to protect the cell against further clonal evolution. Finally, the relevance of the chromosome changes in the multistage process of blastic conversion is discussed, and the breakpoints of secondary changes recorded so far are reviewed and examined. It appears that certain chromosome regions are more often affected; these might contain genes of critical importance for the final malignant progression. Molecular biology may provide insight, in the future, on the nature and expression of involved genes.

Blast Crisis↗

Hidden chromosomal aberrations are rare in primary myelodysplastic syndromes with evolution to acute myeloid leukaemia and normal cytogenetics.

In myelodysplastic syndromes (MDS) a normal karyotype by cytogenetic analysis (CA) corresponds to a low cytogenetic risk for acute myeloid leukaemia (AML) evolution, a subset of patients however develops AML. We evaluated the use of interphase fluorescence in situ hybridisation (I-FISH) in 31 patients with evolution from primary MDS to AML and a normal CA at all stages of disease. Monosomy 7 was found in 4/31 cases, one patient had a terminal deletion 5q, each after AML evolution. The low frequency and unclear prognostic value of I-FISH anomalies in MDS related AML suggests that these alterations play a minor role for AML evolution.

Acute Disease↗

Evidence for genetic exchange and hybridization in Trypanosoma cruzi based on nucleotide sequences and molecular karyotype.

Trypanosoma cruzi is thought to undergo predominant clonal evolution, as determined by population genetics studies. However, this model does not exclude occasional recombination, which existence is strongly suggested by several recent studies. We sequenced a portion of the maxicircle cytochrome b (CYb) gene and of the nuclear rRNA promoter region from representative strains of six T. cruzi genetic lineages isolated from anthroponotic environments and man (lineages IIb, IId and IIe), sylvatic environments (lineages IIa and IIc) or both (lineage I). Phylogenetic analyses based on the two genes were incongruent. Remarkably, in lineage IIe, CYb and rRNA sequences were very closely related to those of lineages IIc and IIb, respectively. One stock of lineage IId showed rRNA sequence heterogeneity, with both IIb-like and IIc-like copies. Analysis of the size variation of six distinct pairs of putative homologous chromosomes revealed a bimodal distribution of chromosomal sizes across T. cruzi. Notably, stocks of lineages IId and IIe had several chromosomal pairs distributed in distinct modes, with the corresponding modes individually found in lineages IIb and IIc. Together, these data indicate the origin of lineages IId and IIe by hybridization between representatives of lineages IIb and IIc. CYb and rRNA sequences clustered into three and four major lineages, respectively. Data were in agreement with the distinction of six genetic lineages, but not with their proposed grouping into two primary lineages, as lineage II was not monophyletic. Based on a CYb substitution rate of 1% per million years (Myr), the major lineages are estimated to have diverged around 10 million years ago.

Animals↗

Evolution of chromosomal variation in cottontails, genus Sylvilagus (Mammalia: Lagomorpha). II. Sylvilagus audubonii, S. idahoensis, S. nuttallii, and S. palustris.

Chromosomes from cultured fibroblasts of four cottontail species (Sylvilagus audubonii, 2n = 42; S. idahoensis, 2n = 44; S. nuttallii, 2n = 42; and S. palustris, 2n = 38) were analyzed using G- and C-banding techniques. The evolutionary restructuring of the genomes of these species was traced by comparing their banded chromosomes to those of Lepus saxatilis, a species of hare in which the leporid ancestral karyotype is thought to have been conserved. Chromosomal evolution appears to have proceeded primarily through changes in the amount and distribution of heterochromatin and through fixation of Robertsonian fusions. Excluding heterochromatic differences, S. audubonii and S. nuttallii are karyotypically very similar, as are S. aquaticus and S. palustris (previously reported). The genome of the taxonomically controversial species S. idahoensis, compared to other cottontail species, is markedly impoverished in C-band material. These data and those of cottontail species previously described in the literature are incorporated in two alternative phylogenetic schemes.

Animals↗

Sequential karyotype study on Ph-positive chronic myelocytic leukemia. Significance of additional chromosomal abnormalities during disease evolution.

Twenty-eight patients with Ph-positive chronic myelocytic leukemia (CML), who all died of the disease, had cytogenetic studies throughout the progression of the disease: at diagnosis, during chronic phase (CP), accelerated phase (AP), and blastic transformation (BT). The aim of this sequential study was to appreciate the frequency and the significance of additional chromosomal abnormalities (ACA) during CML evolution, especially in the CP. In our series ACA were rare (five of 28 patients) and simple (four of five) in CP. They were much more frequent and complex in AP (11 of 16) and in BT (22 of 24) with complex abnormalities (13 of 24). In CP, ACA predictive value for metamorphosis was poor: only three of 13 patients had ACA within 1 year before BT, and only two of 11 within 1 year before AP. ACA were mainly observed during the last period before BT: ten of 17 patients studied within 6 months prior BT had ACA, but by then two of three were in AP. ACA, especially when complex, appear to be a hallmark of CML metamorphosis.

Adult↗

Major chromosome homeologies between Muridae and Cricetidae.

The presumed ancestral karyotype of Muridae, previously reconstructed, is compared with that of a selected Cricetidae species, Akodon a arviculoides. Most of the chromosomes of the presumed ancestral chromosomes of Muridae are homeologous to chromosome arms or segments in the Akodon karyotype. This result strengthens the validity of the reconstruction of the ancestral karyotype for both Muridae and Cricetidae.

Animals↗

[Simultaneous study of karyotype and bone marrow histology in chronic myeloid leukemia with Ph1 chromsome. (author's transl)].

This study was devoted to the simultaneous examination of the karyotype and the bone marrow histology in 33 patients suffering from chronic myeloid leukemia with the Ph1 chromosome. Some patients were evaluated in the beginning of the disease, others after evolution and treatment and some at both times. Supplementary abnormalities of the karyotype occurred in some patients before any treatment, but in most after evolution and treatment. The abnormalities encountered consisted in hypodiploidies, modifications of chromosome structure and hyperdiploidies. The additional abnormalities of the karyotype were in the majority of the patients accompanied by a bone marrow histology characterized by more pronounced blastic infiltration and precollagen fibrosis and evidence of bone lesions. The picture realized by the karyotype and the bone marrow histology allows a better evaluation of the evolution and the prognosis is individual cases, especially of the likely hood of the acute blastic transformation.

Adolescent↗