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I Barrai

Publications and source records attributed to I Barrai.

At least 19 recordsLinked to original sources
PubMed1992

Enrichment of oligonucleotide sets with transcription control signals. II: Mammalian DNA.

We studied the frequency distribution of oligonucleotides 10 bp long in a sample of 1.6 Mb of mammalian genes, containing 579 sequences from GenBank(R) 55.0, with the aim of detecting transcription control signals. 2216 decamers had a frequency higher than 10 times the mean and were subjected to further statistical analysis. For each of the 2216 decamers (parents), we counted the individual frequencies of the 30 decamers differing from the parent by one base mutation (progeny) and then calculated two variance/mean chi squares for the progeny, with and without the parent. We then studied the distribution of the ratio between the two chi squares. Out of 2216 decamers, 346 had a chi square ratio of 1.9 or larger. In this final set, which corresponds to less than 0.033 per cent of all possible decamers, 18 were found to contain 23 eukaryotic transcription control elements 5-10 bp of length, such as Sp1 and others. Furthermore, when compared to 210 random sets containing 346 decamers, this set contains a highly significant excess of the longer signals.

Algorithms↗
PubMed1992

Genetic structures in the Po Delta: principal components, systemic functions and the relative age of the beta-thalassemia polymorphism.

The principal component representations of the genetic structure of the human population of the Po Delta, obtained from 7 polymorphic loci, are compared with the representations obtained from the systemic function of gene frequencies devised by Womble 1951. It is noted that, when tridimensional representations are used, some consistency is visible in the results of the two methods for the description of the genetic population structure in the area under study. Both methods indicate that the present structure of the balanced polymorphism for beta-thalassemia in the area appears to be more recent than the structure of the neutral polymorphisms studied.

Alleles↗
PubMed1992

The analysis of the joint effect of substances on reversion systems and the assessment of antimutagenicity.

The statistical methods for the analysis of mutagenicity and carcinogenicity underwent considerable theoretical-practical development following the need for assessing the mutagenic and carcinogenic potential of substances. Antimutagenicity is investigated through the analysis of respondents in dose-response assays, when two different molecules are administered separately and as a mixture to a respondent system. When the number of respondent units is high, and doses are orthogonal, it is possible to apply simple models such as analysis of variance. This is not always possible or common, and alternative approaches have been developed, based on multiple regression and on tables of proportions. In this work, some of the most frequently used methods for the assessment of joint responses are reviewed, particularly those based on multiple regression, such as the method of Shaeffer et al. and the method of Hass et al. In order to illustrate these methods, joint responses of perylene and cyclopentapyrene, of N-acetylcysteine and dinitropyrene, and of N-acetylcysteine and extracts from diesel exhausts were analyzed. An antagonistic effect of perylene on the action of CPP was detected by the algorithm of Shaeffer et al. The effect is not multiplicative, i.e., it is not proportional to the product of doses. The antimutagenic effect of N-acetylcysteine on dinitropyrene is multiplicative, as detected by the method of Hass et al. The latter reveals that the inhibition by N-acetylcysteine on the mutagenic effect of extracts from diesel exhausts is also multiplicative.

Acetylcysteine↗
PubMed1992

Skin cytogenetic assay for the detection of clastogens-carcinogens topically administered to mice.

A method for assessing the effect of clastogens on mouse skin epidermal cells was devised and applied. Toxic and mutagenic responses in epidermal cells were tested using two known mutagens and carcinogens, urethane (URE) and 7,12-dimethylbenz[a]anthracene (DMBA). Cell generation time, sister-chromatid exchanges (SCE) and chromosomal aberrations (CA) after topical and intraperitoneal (i.p.) treatment were measured in epidermal and bone marrow cells. After topical administration both tissues responded similarly, whereas after i.p. treatment skin cells were less responsive than bone marrow cells. However, the results indicate the validity of this new cytogenetic approach for the assessment of the genotoxicity of compounds applied directly to skin.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Genetic transmission of colorectal cancer: exploratory data analysis from a population based registry.

Classical segregation analysis was conducted on 605 families of probands with colorectal carcinoma ascertained through the Cancer Registry of the Province of Modena in Italy. The families were classified as 28 suspected hereditary non-polyposis colorectal cancer (HNPCC) syndromes and 577 presumed non-HNPCC. In 11 of these, both parents had colorectal carcinoma, in 130 one parent was affected, and in 436 both parents were normal. In the suspected HNPCC families, segregation was compatible with dominant transmission of susceptibility to carcinoma. In families with one parent affected, the segregation frequency was almost exactly equal to the frequency of segregation in families where both parents were normal. The model of dominant transmission of susceptibility through a major gene with greatly reduced penetrance in heterozygotes fitted the data acceptably.

Colorectal Neoplasms↗
PubMed1992

Genetic structures in the population of Veneto.

The genetic structures of the population residing in the provinces of Venice and Rovigo in the Veneto region at the north of the Po delta in Italy was studied in 1,210 individuals residing in 18 sampling areas, using the phenotype and gene frequencies of 7 red cell enzymes: acid phosphatase (ACP1), esterase D (ESD), glyoxalase I (GLOI), glutamic-pyruvic transaminase (GPT), 6-phosphogluconate dehydrogenase (6-PGD), phosphoglucomutase 1 (PGM1), and phosphoglycollate phosphatase (PGP). For the analysis of the distributions of phenotype and gene frequencies, standardized variance and kinship profiles were used. It was found that the genetic differentiation within each province is low, and that only two systems, GPT and PGP, are significantly different between the two provinces. The samples studied seem to belong to a mainly homogeneous population.

Erythrocytes↗
PubMed1991

Frequencies of codons in histones, tubulins and fibrinogen: bias due to interference between transcription signals and protein function.

The distribution of codons was studied in 65 proteins: 48 histones, 14 tubulins, and three fibrinogens, With the methodology used, (1) we confirmed that the preterminator state of a codon has no detectable effect on codon bias. (2) The well-known effect of CG suppression was visible. We also found that (3) some codons which are very rare, are equal to parts of known transcription signals. Thus, we advanced that to avoid signal interference, the use of these codons is suppressed when a synonymous codon is available. In addition we found that in the whole series of codons, transcription signals are less frequent than in a random sequence of equal composition. Finally we observed (4) that tryptophan is absent in histones. This absence was related not to the TGG codon itself, but to characteristics of the amino acid. We conclude that the functional constraints of a protein can influence, at least for synonymous codon usage, the evolution of its own coding sequence.

Animals↗
PubMed1991

A set of viral DNA decamers enriched in transcription control signals.

We studied the frequency distribution of oligonucleotides 10 bp long in a sample of 620 Kb of viral genomes, containing 102 sequences from GenBank, with the aim of detecting transcription control signals. Two thousand three hundred decamers had a frequency 10 times higher than the mean and were subjected to further statistical analysis. For each of the 2300 decamers (parents), we counted the individual frequencies of the 30 decamers differing from the parent by one base mutation (progeny) and then calculated two variance/mean chi squares for the progeny, with and without the parent. We then studied the distribution of the ratio between the two chi squares. Out of 2300 decamers, 10 times more frequent than average, 479 decamers had a chi square ratio of 1.9 or larger. In this final set, which corresponds to less than 0.05% of all possible decamers, 58 decamers were found to contain viral and eukaryotic transcription control elements, like NF-kB, Sp1 and others. Furthermore, this set contains an excess of signals of length 5, 6, 7, 8, 9 and 10, when compared to 150 random sets, bootstrapped from the same viral genomes.

Algorithms↗
PubMed1991

Reproductive behavior of thalassemic couples segregating for Cooley anemia.

The reproductive behavior in 1984 of families segregating for Cooley anemia in Ferrara was compared with that of a control group of families, matched for some biological variables which affect fertility. At the resolution power of the sample, it was found that there is no significant difference in these variables due to segregation for Cooley anemia, and it appears that there is no longer significant reproductive compensation in thalassemic couples, although a tendency to compensate does still exist. The increased life span of children affected by Cooley anemia, due to improvements in treatment in the past decade, is probably the main reason why the compensatory reproductive behaviour of the past has almost disappeared.

Adult↗
PubMed1991

Epidemiology of infant deaths due to congenital malformations: Italy 1958-1981.

The spatial and temporal distribution of infant death rates attributed to the single cause of congenital malformation (DCM) in Italy was studied for the period 1958-1981. Variation of DCM rates in this period was investigated for the whole country, for the three main geographical areas of the North, Center, and South, and for each of the 18 Italian regions (there are 20 administrative regions, but in this study Abruzzo were pooled with Molise and the Aosta Valley with neighbouring Piedmont). It was found that DCM decreases significantly with time. The decrease is considerable in the North and the Center of the country, whereas in the South temporal variation is minimal. There is a marked decrease of the variance of the DCM rates between regions with later years, possibly indicating a tendency to equalization of environmental effects in a large part of the peninsula.

Congenital Abnormalities↗
PubMed1991

Correlations between 15 polycyclic aromatic hydrocarbons (PAH) and the mutagenicity of the total PAH fraction in ambient air particles in La Spezia (Italy).

Airborne particulate matter has been monitored 4 times a month for 1 year (1988) in the city of La Spezia (Italy). The polycyclic aromatic hydrocarbon (PAH) fractions were extracted, purified and characterized for the content of 15 individual PAH. In general when concentrations of individual PAH were compared statistical correlation was obtained. Mutagenicity studies were performed by the use of the Ames plate test with the Salmonella strains TA98, TA100, TA98NR and TA98DNP6 with and without metabolic activation (S9 mix). The TA98 strain was by far the most responsive and the S9 mix was absolutely required as expected when PAH are assayed. Besides mutagenicity, toxicity was also considered and it proved to be correlated with mutagenicity in TA98, +S9. The TA98NR and TA98DNP6 strains showed no appreciable differences from the parental strain TA98 indicating the absence of significant amounts of direct-acting nitro derivatives in our PAH samples. Of the 15 PAH considered in this study the amounts of cyclopental[c,d]pyrene (CPP) correlated best with mutagenicity. The role of CPP in contributing to the indirect mutagenicity of urban air PAH samples is discussed.

Air Pollutants↗
PubMed1991

Kinship structures and migration in the Po Delta.

The kinship analysis of seven genetic systems in the province of Ferrara permits some considerations on the possible chronology of emergence of their polymorphisms in the area. It is proposed that, assuming neutrality of these systems, and under several restrictions, the emergence by migration of the polymorphisms in the seven systems ACP, ESD, GLO, GPT, PGD, PGM1, PGP might have had the following sequence: PGP and GLO and possibly PGD; PGM1 and GPT; ACP and ESD. All polymorphisms must be older than the beta-thalassemia polymorphism in the area.

Alleles↗
PubMed1991

Linkage of biopsy, cancer, and population records aimed at the estimation of family risks in neoplasia: a pilot study.

STUDY OBJECTIVE: The aim was to link individual demographic and medical records into sibships to obtain the sibling distribution of biopsies and cancers, and thereby calculate heritability and recurrence risks in families, thus aiding early diagnosis and prevention of cancers. DESIGN: The 157,823 individual records of the inhabitants of the town of Ferrara in Italy were automatically linked into 106,821 sibships. A 10% sample (10,842 sibships) was then extracted from the distribution of sibships and tabulated, for linkage to medical records. PATIENTS: The biopsy records at the Institute of Pathological Anatomy of the University of Ferrara were manually linked to cancer records and then to sibships. It was possible to construct the distribution of 2062 biopsies and of 829 cancers in sibships. RESULTS: From the distribution of biopsies and tumours in sibships, it was possible to estimate the incidence of tumours in the population (0.052) and in siblings of affected (0.083), and to apply to such distributions current methods for the estimate of heritability (h2 = 0.246) and of recurrence risks of tumours in sibships, age independent. CONCLUSIONS: The study shows that the procedure resulting in the estimation of incidences and recurrence risks for tumours could be completely automated, and extended to whole populations and homogeneous subgroups in post industrial cultures.

Biopsy↗
PubMed1991

Reproductive behaviour of families segregating for Cooley's anaemia before and after the availability of prenatal diagnosis.

The reproductive behaviour of couples with heterozygous beta thalassaemia, with at least one affected child, was investigated for the period 1955 to 1984 and was compared to the behaviour of control couples matched for age, age at marriage, and presence of at least one child. The comparisons were made as a function of knowledge of the risk and availability of prenatal diagnosis and abortion. It was found that the couples segregating for Cooley's anaemia, before knowledge of the risk, had a higher reproductive rate than that of control couples. Knowledge of the genetic risk had a different effect on reproductive behaviour in the 1950s from that in later years. The difference was attributed both to the influence of cultural factors and to technical, therapeutic, and diagnostic advances.

Abortion, Eugenic↗
PubMed1990

Human HLA-DR alpha gene: a rare oligonucleotide (GTATA) identifies an upstream sequence required for nuclear protein binding.

Synthetic oligonucleotides containing putative regulatory sequences are currently employed to identify and isolate genes coding for nuclear binding factors. Upstream DNA sequences of eukaryotic genes required for transcriptional activity and tissue specificity can be identified by means of biochemical techniques as well as computer analysis using homology searching. An alternative approach has been recently proposed by our research group. Scanning DNA sequences 1.8 megabases in length from a Genetic Sequence Data Bank, we have identified rare oligonucleotides 5 base pairs (bp) long, which are localized within or close to regulatory segments in mammalian promoters. In this paper we demonstrate that the rare GTATA sequence identifies an upstream region of the HLA-DR alpha gene which operates in conjunction with the sequence AGAAGTCAG, homologous to a box found in many interferon-inducible genes, in binding nuclear proteins.

Base Sequence↗
PubMed1990

Oligonucleotide correlations between infector and host genomes hint at evolutionary relationships.

The frequencies of oligonucleotides of length 3-6 were studied in 211 sequences of human DNA (659 kilobases), 22 sequences of DNA of human viruses (120 kbs), in 181 sequences of E. coli (442 kbs), and in 42 sequences of phages of E. coli (137 kbs). The sequences were obtained from Genbank(R) 48. The observed frequencies (O) were compared to the expected frequencies (E) obtained in two ways: 1) according to nucleotide composition for each series, and 2) according to first order Markow chains for triplets, second order for quadruplets, and third order for quintuplets and sextuplets. The ratio O/E was obtained for each oligonucleotide. Then, the correlation between the ratio O/E in a pair of series was calculated. Strong correlations were observed for sequences of man and human viruses, and for E. coli and its phages. Other correlations were small. For higher order Markov chains, there is indication of some correlation also between viruses and phages. It was concluded that through analysis of parallel oligonucleotide series it may be possible to infer some of the complex evolutionary relationships existing between cells and their infectors beyond the level of codon usage.

Base Composition↗
PubMed1990

Genotoxicity of two metabolites of benzene: phenol and hydroquinone show strong synergistic effects in vivo.

Possible interactions between hydroquinone (HQ) and phenol (PHE), 2 known benzene metabolites, in inducing micronuclei in mouse bone marrow cells were investigated. HQ and PHE administered alone gave weak and negative results, respectively, at the doses tested. However, simultaneous administration of both compounds caused a considerable increase in the induction of micronuclei as well as an increase in bone marrow toxicity. Using 3 different statistical methods, it was shown that the observed joint effect was significantly higher than additive interaction, and was close to multiplicative interaction. These findings bring further support to the hypothesis that the toxic and genotoxic effects of benzene are produced by several metabolites acting synergistically.

Animals↗