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Biomedical subjects

M Siniscalco

Publications and source records attributed to M Siniscalco.

At least 91 records · Page 5Linked to original sources
PubMed1969

Evidence for intergenic complementation in hybrid cells derived from two human diploid strains each carrying an X-linked mutation.

Two male diploid fibroblast strains, each carrying deficiency mutations at different X-linked loci (glucose-6-phosphate dehydrogenase and hypoxanthine-guanine-phosphoribosyltransferase) have been successfully hybridized. The resulting mononucleated hybrid cells have been shown to synthesize both normal gene products, indicating that both X chromosomes are functionally active in the hybrid cells. We believe this is the first reported example of intergenic complementation in fused human diploid cells.

Autoradiography↗
PubMed1966

Population genetics of haemoglobin variants, thalassaemia and glucose-6-phosphate dehydrogenase deficiency, with particular reference to the malaria hypothesis.

The authors report data on the genetic distribution of thalassaemia and of glucose-6-phosphate dehydrogenase deficiency in the populations of certain Sardinian villages, many of which are not only of great antiquity but have maintained isolation for very long periods and therefore possess the following three requirements for suitability for investigation of the possible interrelationships among malaria, thalassaemia and G-6-PD deficiency: a reasonable degree of ethnic homogeneity, availability of reliable demographic data, and availability of malaria-free populations of adequate size and of ethnic background and genetic isolation similar to those of the malarial populations.Investigations including more than 6000 observations in 52 villages demonstrated a positive correlation between the incidences of thalassaemia and G-6-PD deficiency. It is suggested that the genotype that carries thalassaemia and/or the enzyme deficiency may have a high adaptive value in a malarial environment.It is concluded that there is a need further to investigate human genetic structure and the biological fitness of the principal genotype combinations in both existing environments and those that will result from continued cultural evolution.

Genetics, Population↗
PubMedDate not supplied

Human gene mapping and cancer biology.

The topics covered in this paper include: (i) a somatic cell genetics approach for measuring the individual variability in the susceptibility to DNA damage/repair at the level of specific chromosomal sites; (ii) a rationale for a selective chemotherapy and/or immunotherapy of chromosomally unbalanced tumours; and (iii) studies on complementation for sister chromatid exchange (SCE) in roden-human hybrids. Preliminary studies indicate that the 'radiation co-transfer method' for gene mapping can be simplified and used in screening for differences in individual susceptibility to radiation induced chromosomal damage. The second topic is dealt with only speculatively, with the explicit aim of emphasizing a practical application in clinical medicine which may potentially derive from the admittedly esoteric activity of gene mappers. The third topic summarizes a somatic cell genetic approach to the study of SCE in mammalian cells. The high rate of SCE observed in an established rodent cell line can be fully suppressed after hybridization with SCE-normal human cells. However, this suppression can be fully removed after extensive loss of the human chromosome complement. Correspondingly, the high SCE rate of Bloom syndrome cells is fully corrected after hybridization with a Chinese hamster line, though the chromosomes of the latter parental cells continue to exhibit in the hybrid cells the moderately high rate of SCE which is typical of this animal line. These complementation experiments indicate that more than one lesion can upset the normal chromatid replication of mammalian cells and lead to high SCE. The experimental studies described promise to be of significant help for studies on the biology of SCE in general and offer a suitable way of screening for possible genetical heterogeneity among different Bloom syndrome patients.

Chromatids↗
PubMedDate not supplied

Fragile-X mutation and Klinefelter syndrome: a reappraisal.

To date the concurrent presence of the fragile-X and the Klinefelter syndromes in the same individual has been found at least 8 times either in the course of screening for the fra(X) condition in mentally retarded males or among the relatives of fra(X) propositi. Given the high frequency of both events in the general population and the heterogeneous approaches with which the above cases were ascertained, it has not been possible to determine unequivocally so far whether the finding is purely coincidental or the expression of some underlying biological relationship. To evaluate the issue, we have screened a large population of institutionalized mentally retarded males for microorchidism, and submitted to a full karyotype analysis and fra(X) testing the patients that were found to have marked bilateral microorchidism. Thus, in a total of 32 microorchidism patients identified among 1115 mentally retarded males, we found 6 to have a 47,XXY chromosome complement in all (or in most) of their cells, with one of them having also the fra(X) marker in 9% of the metaphases examined. In addition, another bearer of the fra(X) marker (but only in 4% of his metaphases) was found among 26 47,XXY mentally normal males ascertained throughout routine cytogenetic analysis of males with microorchidism referred to our genetic counseling unit during the last 10 years. In our laboratory the fra(X) marker has never been observed with such a frequency in a total of several hundred normal XY males and XX females studied as control cases in the course of previously reported family and population studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Physical and genetic mapping of the CDR gene with particular reference to its position with respect to the FRAXA site.

This study narrows down the localization of the gene coding for the cerebellar degeneration-related protein (CDR 34) to the upper boundary of the FRAXA and reports the finding of two common RFLPs respectively identified at an RsaI site flanking the 3' end of the gene and at a Hincll site flanking its 5' end. Segregation analysis carried out in the CEPH-pedigrees for the new CDR/RsaI-RFLP versus other polymorphic loci of the region has established a tight linkage with the markers DXS105/DX98 and absence of measurable linkage with two clusters of markers respectively located proximally to the FRAXA (F9, DXS102, DXS51, and DXS369) or distally to it (DXS52, DXS304). In addition, two recombinants were found among 23 scorable sibs identified in the Sardinian pedigrees segregating for the Martin-Bell Syndrome (MBS) and the CDR/RsaI variants. The overall evaluation of the in situ and genetic data reported suggest that the CDR locus 1) is located at the upper boundary of the FRAXA site; 2) is distal to DXS51 and proximal to DXS 389; and 3) segregates in a close linkage association with the loci DXS98 and DXS105 and, to a lesser extent, with the locus for MBS.

Antigens, CD34↗
PubMedDate not supplied

Premutation for the Martin-Bell syndrome analyzed in a large Sardinian family: II. Neuropsychological and behavioral data.

We describe the neuropsychological and behavioral profiles of 48 critical members of a previously reported Sardinian pedigree [Filippi et al., 1991], in which the fully manifested Martin-Bell syndrome (MBS), observed among males of the latest generations, is clearly the result of step-wise mutational events occurred repeatedly along the X-chromosome pathway linking all of them to a common ancestress, who must have been heterozygous for a fragile X (FRAX) premutation. We found that the unquestionable presence in the family of normal transmitting males and females could not be determined on the basis of neuropsychological and behavioral data alone. However, we think that the large variation observed in the expression of most diagnostic parameters among the MBS patients and their close female relatives in this family, could by itself be a connotation of the genome instability which characterizes the FRAX region in pedigrees segregating for the FRAX premutation(s) and mutation(s).

Behavior↗
PubMedDate not supplied

X-linkage of steroid sulphatase in the mouse is evidence for a functional Y-linked allele.

In the human there is an X-linked gene affecting steroid sulphatase (STS) activity which, when deficient, is associated with X-linked congenital ichthyosis. The gene (STS) is located on the distal tip of the short arm and is only partially inactivated when it is on the inactive X-chromosome. In the mouse, the genetics of STS are not clear; the results of one study using XX:X0 oocyte comparisons indicated X-linkage, but three other studies using STS variants have produced segregation data compatible with autosomal linkage of murine STS. Here we present the results of STS assays of crosses of deficient C3H/An male mice to normal X0 animals which demonstrate X-linkage of STS in the mouse and indirectly indicate the existence of a functional STS allele on the Y-chromosome which undergoes obligatory recombination during meiosis with the X-linked allele.

Animals↗
PubMedDate not supplied

[The human genome project: reflections of an expert].

Just about five years have elapsed since a handful of leading scientists began to discuss the opportunity to launch the Human Genoma Program, an international organized effort to characterise all the genetic material--DNA--of the human organism. Today, the project is well under way with the participation of tens of thousands investigators from all over the world and the direct involvement of major sponsoring bodies such as the United States Department of Energy and the National Institutes of Health, the European Economic Council, the USSR Academy of Sciences and the Governments of France, Great Britain, Italy, Japan and Spain. Yet, the reactions of the general public to the Project is, to say the least, very diverse. Some are sure of its positive impact on the prevention and cure of inherited diseases, some fear its infringence on individual privacy, but the majority remains totally indifferent. Since the lack of adequate information is the common denominator at the root such different reactions, this Editorial will try to summarise the major issues of the Project and their impact on Society.(ABSTRACT TRUNCATED AT 250 WORDS)

Human Genome Project↗