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A Paoloni-Giacobino

Publications and source records attributed to A Paoloni-Giacobino.

At least 19 recordsLinked to original sources
PubMed2006

The role of DMDs in the maintenance of epigenetic states.

An important aspect of genome reprogramming is the establishment and maintenance of gamete-specific DNA methylation patterns that distinguish the parental alleles of imprinted genes. Disrupting the accurate transmission of genomic imprints by interfering with these methylation patterns causes severe defects in fetal growth and development. The inheritance of sex-specific DNA methylation patterns from both parents is thus a fundamental molecular definition of genomic imprinting. The other cardinal aspect is the regulation of imprinted gene expression over a long genomic distance, spanning a few clustered imprinted genes. There is converging experimental evidence that differentially methylated domains (DMDs), located in non-coding regions of imprinted genes, are involved in both processes. As such, DMDs are the imprinting backbone upon which the fundamental processes of sex-specific methylation and imprinted gene expression are built.

Animals↗
PubMed2006

Six cases of cryptic subtelomeric translocations in four families: the use of subtelomeric FISH probes as a diagnostic tool.

Finding the diagnosis in children with mental retardation and a normal karyotype, whether or not associated with dysmorphic features, is important for defining an eventual syndrome and for genetic counselling of the families. Telomeric re-arrangements may be a common and underestimated-to-date cause of non-syndromic mental retardation. Using a FISH-based approach combining subtelomeric probes, we report the detection of 4 cases of cryptic translocations t(2;10)(p25.3;q26.3), t(4;17)(p16.2;q25), t(4;20)(p16.2;q13) and t(5;7)(p15.3;q36) associated with MR and dysmorphic features. We discuss the usefulness of subtelomeric FISH in children with unexplained delayed psychomotor development, when the genetic cause remains unknown and the karyotype is normal.

Abnormalities, Multiple↗
PubMed2005

[A conflict within the genome, the battle of the sexes?].

It is estimated that 100 to 200 genes in the human genome are imprinted. These are expressed only from one parental allele, although having the same DNA sequence. Several of the known imprinted genes have been shown to be involved in fetal and placental growth, and imprinting defects can lead to embryonic, developmental defects as well as cancer. This mechanism of gene regulation probably emerged 150 million years ago in mammals. The reasons for the appearance and maintenance of this phenomenon throughout evolution are still controversial.

Animals↗
PubMed2004

Parenteral nutrition practices in hospital pharmacies in Switzerland, France, and Belgium.

OBJECTIVE: Important changes in administering total parenteral nutrition (PN) admixtures have occurred over the past decade. This study describes hospital pharmacists' practices in France (F), Switzerland (CH), and Belgium (B). METHODS: From the responses received using a standardized questionnaire, (n = 378) we determined the origin, types of container used, and choice of PN formula (standard versus tailor-made) and the type of quality control and the existence of nutrition support teams. RESULTS: The mean response rates were 55.6% (CH), 30.5% (F), and 24.5% (B). Standard formulas were used mainly for adult patients (CH, 86%; F, 79%; B, 86%), whereas approximately 50% of tailor-made PN bags were used for children. Single-compartment or multicompartment bags or glass bottles contained standard formulas. Most standard formulas were provided by industry, apart from (B), where 50% of PN solutions were compounded by hospital pharmacies. Single-compartment bags contained generally tailor-made formulas produced exclusively by hospital pharmacies in (CH) and (B), whereas 33% were provided by industry in (F). Quality controls were mostly visual and occurred in 75% to 95% of hospitals. Nutrition support teams were present in 32% to 45% of hospitals. CONCLUSION: The choice, origin, and type of container used for PN formulas were highly variable among countries. However, the use of standard formulas in bags was predominant in (CH) and (B). The function of nutrition support teams was similar in (F), (CH), and (B).

Belgium↗
PubMed2003

Genetics and nutrition.

The understanding of the role of nutrients on DNA stability, repair and on the different gene expression processes recently became more prominent in nutritional science. Nutrients and the genomics interact at two levels. Nutrients can induce gene expression thereby altering individual phenotype. Conversely single nucleotide polymorphisms, in a range of genes important in inflammation and lipid metabolism, alter the bioactivity of important metabolic pathways and mediators and influence the ability of nutrients to interact with them. The study on single effects of nutrients on the individual's phenotype as well as the serial analyses of gene expression patterns in response to specific nutrients will help us to understand how metabolic homeostasis is maintained. Considering that there is wide variation in the ability of nutritional factors to modulate the expression of detrimental or protective proteins at an individual level, the concept of diet-medication could be developed in the light of a better understanding of nutrient-gene interactions. In this way, 'good responders' and 'poor responders' to diet therapy can be identified. Furthermore, as several vitamins participate in DNA protection and genomic stabilisation, diet-linked therapies could become part of cancer prevention and other treatments with relevant consequences for human health.

Animals↗
PubMed2003

Genomic interactions with disease and nutrition.

The putative influence of genomic factors on the responsiveness to nutrient intake is a newly developed field of research. As well, there is growing interest for determining the interactions between nutrient, inflammation and aging and the possible impact on lifespan and disease development. Inflammation adversely affects health in many diseases with an inflammatory basis, such as atherosclerosis, obesity and type 2 diabetes mellitus. The metabolic effects of inflammation are mediated by pro-inflammatory cytokines. Metabolic effects include insulin insensitivity, hyperlipidemia, muscle protein loss and oxidant stress. Aging is also characterized by an increase in inflammatory stress and contains some of the hallmarks of inflammatory disease. It is also a phase of life when inflammatory diseases rise in incidence. Evidence is accumulating that the individual level of cytokine production is influenced by single nucleotide polymorphisms (SNPs) in cytokine genes. The combination of SNPs might control the relative level of inflammatory stress following inflammatory stimuli and diseases. These genomic characteristics might therefore influence lifespan, morbidity and mortality in diseases with an infectious or inflammatory basis.Recent studies indicate that genotypic factors may influence the effectiveness of such immunonutrients as anti-oxidants and n-3 polyunsaturated fatty acids. A better understanding of this aspect of nutrient gene interactions and of the genomic factors which influence the intensity of inflammation in disease will help in the targeting of nutritional therapy.

Chronic Disease↗
PubMed2003

Pregnancy outcome of 30 fetuses with cystic hygroma diagnosed during the first 15 weeks of gestation.

The goal of the study was to assess the prognostic value of ultrasound finding of fetal cystic hygromas. Thirty cases of septated cystic hygromas were diagnosed at 10-15 weeks gestation by transabdominal ultrasound and followed through pregnancy. The rate of abnormal karyotype was found to be 61% and the global rate of unfavorable outcome, independently of karyotype result, as high as 96%. These data suggest that cautious genetic counselling should be offered when such cystic hygromas are noticed during the first 15 weeks of gestation, even with a normal karyotype.

Adult↗
PubMed2001

Frequency of replication/transcription errors in (A)/(T) runs of human genes.

To estimate the error rate of the gene expression machinery and its possible age-related increase, we compared the occurrence of polymerase errors during replication and transcription in (A)/(T) runs, in DNA and RNA of young and old individuals and of early- and late-passage cultured fibroblasts. We analyzed three human genes: TPRD, TGFBR2, and ATRX containing stretches of (A)8, (A)10, and (T)13, respectively. The error rate was determined by sequencing 100 cloned PCR or RT-PCR fragments from each DNA and RNA sample. The error rates in replication and transcription increased with the stretch length. The pooled error rates for genomic DNA were: TPRD (A)8, TGFBR2 (A)10, and ATRX (T)13: 1%+/-0.41, 15.8%+/-1.3, and 31.3%+/-2.9, while those for RNA were: 3.8%+/-0.5, 19.3%+/-2.1, and 54.3%+/-1.8, respectively. The deletions of one nucleotide were the most frequent errors. In the replication analysis, a significant difference was found in old versus young individuals for the ATRX (T)13. In the transcription analysis, significantly higher error rates were obtained in old versus young individuals for the TPRD (A)8 and TGFBR2 (A)10. For these genes, the error rate in RNA isolated from fibroblasts was significantly higher than that in blood. The data show a trend of age-related increase in replication/transcription errors; however further studies are necessary to confirm this hypothesis, since the sample size is small. This imperfect fidelity of the gene expression process may explain the evolutionary disadvantage of nucleotide repeats within coding sequences, and that these repeats are targets for mutations in human diseases.

Adult↗
PubMed2001

Suicide attempts and the tryptophan hydroxylase gene.

Tryptophan hydroxylase (TPH) is the rate-limiting enzyme of serotonin synthesis. In this case-control study, we investigated whether the TPH gene was a susceptibility factor for suicidal behavior. Seven polymorphisms spanning the entire gene were studied in a case-control study including 231 individuals who had attempted suicide and 281 controls. Significant associations were found between variants in introns 7, 8 and 9 (chi(2) = 11.2, df = 1, P< 0.0008 for the allele distribution; these loci are in complete linkage disequilibrium) and in the 3' noncoding region (chi(2) = 30.94, P = 0.0014) and suicide attempt. The association was strongest for subjects who had attempted suicide by violent means and who had a history of major depression. No significant association was observed between suicide attempts and polymorphisms in the promoter, intron 1 and intron 3. The results presented here, and those of previous studies, suggest that a genetic variant of the 3' part of the TPH gene may be a susceptibility factor for a phenotype combining suicidal behavior, mood disorder and impulsive aggression.

Adult↗
PubMed2000

Familial t(6;21)(p21.1;p13) translocation associated with male-only sterility.

A 38-year-old male with primary infertility was referred for cytogenetic investigation. Karyotype analysis revealed a 46,XY,t(6;21)(p21.1;pl3) translocation. The Ag-nucleolar organizer regions (NORs) banding technique demonstrated that the 21p NORs were retained in the derivative and actively transcribed. Family studies showed that three brothers, two sisters and their mother carried the t(6;21). All carrier males suffered from primary infertility with severe oligoasthenoteratospermia or azoospermia, whereas at least two of the three carrier women were fertile. The region of the translocation breakpoint was narrowed down cytogenetically and by fluorescence in situ hybridisation as 21p13 and 6p21.1. Southern blot analysis showed that the gene ZNF165, which maps to this region and which is specifically expressed in the testis, was not disrupted by the translocation. However, studies performed on testicular biopsy showed spermatocyte meiosis anomalies. We discuss the possible mechanisms by which the translocation might affect meiosis in spermatogenesis and lead to infertility.

Adult↗
PubMed2000

Identification and analysis of new sequence variants in the human tryptophan hydroxylase (TpH) gene.

The tryptophan hydroxylase (TpH) gene codes for the rate-limiting enzyme in serotonin biosynthesis. It is one of the major candidate genes for psychiatric and behavioral disorders. A polymorphism in TpH intron 7 has been shown to be associated with suicidal attempts, aggressive behavior and psychiatric illnesses. By systematically screening the TpH genomic sequence, we identified and confirmed an earlier report of four variants in the promoter region and localized six new sequence variants, ie two in intron 1b, one in exon 1c, one in intron 8, one in intron 9 and a microsatellite in the 3' region, 5687 bp downstream of the last exon 11. We analyzed these polymorphisms, as well as the one in intron 7, by Single Strand Conformation Analysis, microsatellite or restriction analysis in a collection of 175 West European Caucasian healthy subjects. The four variants in the promoter region are in complete linkage disequilibrium (frequencies of G-T-G-T and T-C-A-G haplotypes are 0. 41 and 0.59, respectively). Deletion of GTT in intron 1b is rare (0. 7%) and so not informative. The rarer allele T of intron 1b polymorphism T3792A has a frequency of 0.34 and is in partial linkage disequilibrium with the more common alleles of intron 7, 8 and 9. The polymorphisms of these three introns are in complete linkage disequilibrium and the frequencies of haplotypes A-T-C and C-C-T are 0.36 and 0.64 respectively. We detected 10 different alleles in the microsatellite localized in the 3' region; allele '194' is in partial linkage disequilibrium with haplotype A-T-C of introns 7, 8, and 9. Analysis of these different polymorphisms will constitute an important tool for future studies between the TpH gene and psychiatric disorders. Molecular Psychiatry (2000) 5, 49-55.

Alleles↗
PubMed2000

A case of 45,X Turner syndrome with spontaneous ovulation proven by ultrasonography.

A well-documented case of non-mosaic Turner syndrome, with spontaneous pubertal development and ovulatory cycles is reported. Mosaicism could be excluded both by karyotyping of 172 metaphases of blood lymphocytes and fibroblasts, and by fluorescence in situ hybridization, using an X-centromeric probe, in 200 blood lymphocyte nuclei. This Turner syndrome patient underwent normal pubertal development, with spontaneous menarche at 14 years, followed by regular monthly periods. Hormonal measurements performed during puberty were consistent with the patient's pubertal development. At the age of 26 years the patient was referred for complete fertility evaluation. Detailed hormonal analyses were performed in a given cycle. They showed midluteal phase estradiol and progesterone values within the range corresponding to normal ovulation and corpus luteum function. In the same cycle, pelvic ultrasonography was also performed at days 13, 15 and 18. It demonstrated a spontaneous ovulation, with follicular rupture that occurred between days 15 and 18. This is the first report of a spontaneous ovulation in Turner syndrome evidenced, not only by hormonal analysis, but also by ultrasonographic demonstration of follicular rupture.

Adult↗
PubMed1999

A proven case of materno-foetal transfusion determined by cytogenetic and DNA analysis.

We report a case of materno-foetal transfusion in a phenotypically normal male foetus after death in utero at the 35th week of gestation. We have used cytogenetic and polymerase chain reaction (PCR) microsatellite analysis to determine the presence of maternal cells in foetal blood collected by intracardiac puncture. In the intracardiac blood sample, maternal cells were estimated to comprise between 5 and 10% of nucleated foetal blood cells. When there is a suspicion of foetal genetic pathology, it is necessary to be aware that the foetal blood karyotype may be misrepresentative, as the analysed blood cells can indeed be of maternal origin.

Adult↗
PubMed1999

Pure partial trisomy 5q33-->5q35 resulting from the adjacent-1 segregation of a paternal (5;14)(q33;p12) translocation.

A 14-year-old male was referred for evaluation of mental retardation with short stature and dysmorphic features. His karyotype was 46,XY,der(14)t(5;14)(q33;p12)pat, resulting in a pure partial 5q33-q35 trisomy due to the adjacent-1 segregation of a paternal balanced translocation. Paternal blood karyotype revealed a balanced translocation t(5;14)(q33;p12) retaining Ag-Nors. To date, only two cases of pure partial 5q trisomies spanning this region have been reported. Analysis of these cases and the one we report does not allow the delineation of a specific phenotype.

Adolescent↗