Cytogenetic analysis in human bone marrow transplantation.

Bone marrow transplantation (BMT) is a therapeutic process used to treat a variety of hematologic diseases. After BMT, the documentation of engrafting with the use of genetic markers is obligatory. C-band polymorphism is an excellent genetic marker because it occurs with high frequency in all populations studied and shows a high stability in vitro and in vivo. We studied a total of 36 patients: 15 with myeloid leukemia and 21 with severe aplastic anemia (SAA), submitted to BMT. The majority of the patients with chronic granulocyte leukemia (CGL; 10/15, 67%) and with SAA (17/21, 81%) showed a frequency of host cells around 15% (CGL) and 8% (SAA) in the first period analyzed (day +30 post-BMT); with a decrease in the others (+90, +180 to CGL and SAA and +365 only to CGL). In our study, the persistence of host cells in these proportions did not imply an unfavorable prognosis. On the contrary, some patients with myeloid leukemia (5/15 33%) and SAA (4/21, 19%) showed high proportions of host cells in one or more periods analyzed. If compared to the first group, these patients had, in general, a poor clinical evolution, with rejections, relapses, and deaths in greater numbers. These results show the important contribution of cytogenetic analysis in the follow-up of patients submitted to BMT.

Transcription of the neurogenic gene mastermind during Drosophila development.

The neurogenic loci of Drosophila encode the components of a cell communication pathway that operates during multiple developmental stages and in numerous tissues. Activation of the pathway is required for inhibitory interactions, during partitioning of cells into alternative pathways of differentiation. Genetic studies of these loci have demonstrated numerous interactions, suggesting a close relationship among the gene products; molecular studies have corroborated some of these ideas. The mastermind (mam) locus shows genetic interactions with several neurogenic loci, yet its role in this pathway is unknown. We have analyzed mam transcription and further characterized the phenotype associated with mam alleles. mam is widely expressed in patterns overlapping those of other neurogenic loci during embryonic and postembryonic development; embryonic transcription is not dependent upon function of neurogenic genes. mam transcription is widespread during most of embryogenesis; however, late embryonic expression appears limited to the nervous system. Central nervous system expression persists at high levels during larval and pupal stages. Widespread transcription is also observed in ovaries and imaginal discs, with enhanced levels just anterior to the morphogenetic furrow of the eye disc. Phenotypic analyses of mam mutations demonstrate a broad phenotypic range and suggest that particular alleles disturb features of the CNS unrelated to neural overgrowth.

Homopolymer length variation in the Drosophila gene mastermind.

Runs of identical amino acids encoded by triplet repeats (homopolymers) are components of numerous proteins, yet their role is poorly understood. Large numbers of homopolymers are present in the Drosophila melanogaster mastermind (mam) protein surrounding several unique charged amino acid clusters. Comparison of mam sequences from D. virilis and D. melanogaster reveals a high level of amino acid conservation in the charged clusters. In contrast, significant divergence is found in repetitive regions resulting from numerous amino acid replacements and large insertions and deletions. It appears that repetitive regions are under less selective pressure than unique regions, consistent with the idea that homopolymers act as flexible spacers separating functional domains in proteins. Notwithstanding extensive length variation in intervening homopolymers, there is extreme conservation of the amino acid spacing of specific charge clusters. The results support a model where homopolymer length variability is constrained by natural selection.