Biomedical subjects
Publications and source records attributed to M Mutsuddi.
Human neurodegenerative disorders are typified by late onset cell loss in specific brain regions and stereotypic neuroanatomical and behavioral aberrations. Recent studies suggest that molecular genetic approaches in Drosophila may shed important new light on conserved mechanisms underlying such disorders.
Expansion of triplet repeats has been seen to underlie several disorders that manifest anticipation. Clinical evidence suggests that anticipation occurs in the major psychoses. We studied the distribution of repeat sizes at the Machado-Joseph disease (MJD) locus in a group of patients with the major psychoses. We did not find any large expansions, though 2 patients had alleles that were two repeats larger than in our controls. The difference in allele sizes was larger in the patient sample as compared to the controls. The effect of such large differences might be of functional significance.
The molecular genetic analyses (PCR and Southern hybridization) of Indian patients with myotonic dystrophy (DM) were carried out to determine the degree of repeat expansion and an attempt was made to correlate the repeat number with disease severity. A scoring system based on the salient clinical features was devised to objectively assess the disease severity. The repeat expansion was seen in 11 of 12 patients examined and showed an inverse correlation with the age of onset confirming the phenomenon of anticipation. This was further established in the two pedigrees studied, clearly demonstrating both clinical and genetic anticipation. The clinical severity score, however, did not correlate well with the repeat number. Nonetheless, such molecular genetic analyses may have immense value as a screening procedure to identify premutations as well as in prenatal diagnoses.
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Developmental expression of the heat shock inducible non-protein coding hsr-omega gene in several larval and adult tissues of Drosophila melanogaster was examined by in situ hybridization to transcripts in intact organs and by X-gal staining in the germline transformants and carrying the lacZ reporter gene under the control of hsr-omega promoter. This gene is expressed in a specific spatial pattern in all the larval and adult tissue types examined; however, its transcripts were specifically absent in certain gonadal cell types like the male as well as female gonial cells and in follicle cells and oocytes in ovary. All polytenised tissues like the prothoracic and salivary glands, certain regions of larval gut and the Malpighian tubules showed a greater abundance of hsr-omega transcripts with a strong hybridization in nuclei. Our results with promoter deletion variant germline transformants suggest that a region between -346bp to -844bp upstream contains major regulatory elements for developmental expression of this gene in most of the larval and adult tissues examined; however, this region is not sufficient for its normal expression in male and female reproductive systems. An analysis of the base sequence of the hsr-omega promoter (upto - 844 bp) reveals putative ecdysone receptor element half-sites and two GAGA factor binding sites which may be involved in its developmental expression and its ready inducibility. The widespread expression in most tissue types and the known lethality associated with its homozygous deletion, suggest that the variety of non-protein coding transcripts of the hsr-omega gene have vital "house-keeping" functions.
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A chromosomal element (C) of an interspecific hybrid of D. miranda (females) and D. persimilis (males) represented a unique situation, where between its two homologous, one derived from an X chromosome (X2 of miranda) and the other from an autosome (3rd chromosome of persimilis). In cytological preparations of polytene nuclei, the X chromosomal homolog in hybrid males exhibited the male-X like inflated structure, known as prerequisite for hypertranscription; whereas the autosomal homolog existed as an haploid autosomal arm. In hybrid females, both the homologs had similar diameter and stainability. This difference in cytomorphology of the X2 homolog between two sexes made the C element potential to transcribe higher in males than in females, raising the inevitable question of compensation. Cellular autoradiography, using 3H-UR, was employed to measure the total transcription of the C element (X2 + 3rd) in hybrid sexes. Results revealed that, although the X2-homolog was hyperactive in males, the total transcription of the C element was equal (relative to autosomal transcription) in both hybrid sexes, and this was achieved in expense of the transcription of the 3rd chromosomal homolog in males. Thus, apart from X-chromosomal and autosomal dosage compensation, the existence of an X-autosomal dosage compensation in Drosophila is evident in the present work.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.