Biomedical subjects
Publications and source records attributed to G Novelli.
Cytogenetic and molecular analyses were carried out in two fetuses with de novo non mosaic dic (Y)(q11.2) and Yqsat. Molecular deletion of the region to which the AZF locus has been assigned was found in the first case.
The expression of myotonin-protein kinase (MT-PK) gene was studied in myotonic dystrophy (DM) muscle and normal controls using a polymerase chain reaction protocol to analyse the 3' intragenic p(CTG) polymorphism. Unaffected individuals show bi-allelic expression, while the sole wild-type allele was transcribed in DM muscle. Our findings support a gene dosage effect in the pathogenesis of the disease.
Recent studies have shown that the gene encoding for the slow skeletal troponin isoform T (TNNT1) is located on the proximal long arm of human chromosome 19 in the myotonic dystrophy (DM) region. In order to test TNNT1 as a candidate gene for DM, we have isolated TNNT1 cDNA from skeletal muscle from two healthy individuals and from two patients with DM. Sequencing of the TNNT1 cDNA from the DM and normal muscle revealed two sequence variants but no transcriptionally significant mutations. This work rules out a defect in the coding segment of TNNT1 as a cause of DM and provides a polymerase chain reaction protocol for studying troponin T gene expression.
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Human papillomavirus (HPV) has been implicated in the development of cervical cancer. Newly developed molecular techniques have facilitated HPV identification and typing of cervical lesions. Several studies have suggested a strong correlation between HPV16 and intraepithelial cervical neoplasia. However, there is no agreement on this point since HPV16 is detected also in normal cervical tissue. We have amplified the L1 region of HPV16 DNA using the polymerase chain reaction (PCR) technique and analyzed the HPV16 prevalence in cytological scrapes of 201 Italian sexually active patients. One hundred twenty-four of these women had normal cytologic and colposcopic examination, while seventy-seven women had normal or abnormal cytology and a cervical lesion detectable by colposcopy. Within this latter group, 25 of 77 women (32.4%) were positive for HPV16 DNA, compared to 11 of 124 samples (8.87%) from women with normal cytology and colposcopy. The present results confirm the high efficiency of the PCR technique in detecting HPV16 DNA from cervical scrapes and suggest that this analysis should become a method of choice in clinical studies.
A PCR protocol has been developed using inosine-containing primers for human papilloma virus (HPV) detection. The HPV16 L1 region from CaSki-positive cells was efficiently amplified by a single reaction and directly analyzed by agarose gel electrophoresis. The method was found to be sensitive and reproducible, and it easy to use for HPV typing and screening.
We report on linkage analysis and haplotype characterization in 40 Italian families with spinal muscular atrophy (SMA). The investigated loci included D5S6, D5S112, D5S39, and D5S76. No evidence of unlinked families was found. Thirty-two (80%) of the examined families were fully informative for prenatal diagnosis and carrier detection. The frequencies of individual alleles did not differ between SMA and normal chromosomes.
Myotonic dystrophy results from expansion of a (CTG)n repeat at the 3' untranslated region of the myotonin-protein kinase gene. We show here the genomic analysis of 322 symptomatic patients with the cDNA-25 probe detecting disease specific EcoRI restriction fragments. The expansion was found in the majority of Italian and Spanish patients (92%). The implications of these results for the detection of symptomatic patients in southern Europe are discussed.
We report the results of a biological and molecular study carried out on 11 Italian families, with a total of 111 individuals in which adult dominant polycystic kidney disease segregates. A restriction fragment length polymorphism analysis was performed. Two families have shown a genetic heterogeneity even if not phenotypically different from the other ones: they resulted unlinked to 16p markers. A prenatal diagnosis has been performed in a family of the linked type.
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In order to better characterize the chromosomic rearrangement of an unbalanced 45XX t(X;22) (q28;q11) DiGeorge patient, a somatic hybrid clone segregating the translocated chromosome was constructed and investigated using X and 22 linked markers. Our study demonstrated that this de novo translocation was from paternal origin. The breakpoint was assigned between DXS296 and IDS loci at Xq28 and between D22S9 and BCRL2 at 22q11. This observation and published data allow to locate a "critical region" for DiGeorge syndrome between these two last loci on 22q11. Our hybrid clone may be a useful tool for mapping new probes arising in this region.
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Linkage analysis and haplotype characterization for the allelic system detected at the 3' creatine kinase muscle type (CKMM) locus were carried out in 59 myotonic dystrophy (DM) families from Italy and Spain. A maximum lod score (zmax) of 21.26 at a recombination frequency (theta) of 0.00 was found. No statistically significant linkage disequilibrium was observed between DM and the RFLPs examined. However, a substantial linkage disequilibrium was found between CKMM-TaqI and CKMM-NcoI sites in these two populations.
We have analysed five Southern European populations (Albanian, Greek, Italian, Spanish and Yugoslavian) for 14 cystic fibrosis (CF) mutations. The most frequent mutations, apart from delta F508, were G542X (6.04%), R1162X (3.61%) and N1303K (3.24%). Each of the other analysed mutations were present at a frequency of less than 1% (R347P, R334W, S549RA, S549I, G551D, R553X and W1282X), and four mutations (D110H, delta I507, S549RT, and S1255X) were not found in this sample. The data presented here allows the use of mutation analysis in 69.5% of Spanish, 58% of Greek, and 56.5% of Italian CF cases.
A clamped homogeneous electric field (CHEF) electrophoresis allowing the separation of DNA molecules in the range of 200 to 3000 kb in size was used to study the biological effects of electric and magnetic fields (EMFs). The results obtained did not show any detectable genomic damage on Saccharomyces cerevisiae.
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The major mutation in the cystic fibrosis (CF) gene is a 3-bp deletion (delta F508) in exon 10. About 50% of the CF chromosomes in Southern Europe carry this mutation, while other previously described mutations account for less than 4%. To identify other common mutations in CF patients from the Mediterranean area, we have sequenced, exon by exon, 16 chromosomes that did not show the delta F508 deletion from a selected panel of eight unrelated CF patients. We describe here one missense and one nonsense mutation, and four sequence polymorphisms. We have also found two previously reported mutations in three chromosomes. Overall, these mutations may account for about 20% of CF alleles in the Italian and Spanish populations. No other mutations were detected in 10 out of 16 CF chromosomes after analyzing about 90% of the coding region of the CF gene, and 39 out of 54 intron/exon boundaries. Therefore, about 26% of CF mutations remain to be identified. In addition we provide the intron/exon boundary sequences for exons 4 to 9. These results together with previously reported linkage data suggest that in the Mediterranean populations further mutations may lie in the promoter region, or in intron sequences not yet analyzed.