Publications by authors named "Silvano Presciuttini"

35 Publications

HYPNOTIZABILITY-RELATED FAAH C385A POLYMORPHISM: POSSIBLE ENDOCANNABINOID CONTRIBUTION TO SUGGESTION-INDUCED ANALGESIA.

Int J Clin Exp Hypn 2020 Jan-Mar;68(1):29-37

Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.

Fatty acid amide hydrolase (FAAH) degrades the endogenous endocannabinoid (eCB) anandamide and might be involved in the response to suggestions of analgesia in subjects with high hypnotizability scores (). Since the A allele of the FAAH C385A polymorphism (rs324420) is associated with lower FAAH activity, it was studied in 21 highs, 66 low hypnotizable individuals (), and 172 individuals not selected for hypnotizability () representing the general population. No significant difference was observed among groups, but the A allele frequency showed a significant trend to increase from lows to controls and from controls to highs. Since eCB small differences can be amplified by eCB interactions with other neurotransmitters, a contribution of the FAAH polymorphism to the highs' analgesia should not be excluded.
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http://dx.doi.org/10.1080/00207144.2020.1682254DOI Listing
January 2021

Disaster victim identification by kinship analysis: the Lampedusa October 3rd, 2013 shipwreck.

Forensic Sci Int Genet 2020 01 5;44:102156. Epub 2019 Oct 5.

Dipartimento di Sanità Pubblica, Medicina Sperimentale e Forense, Sezione di Medicina Legale e Scienze Forensi, Università di Pavia, Pavia, Italy. Electronic address:

On October 3rd, 2013 a boat carrying more than 500 migrants coming mostly from the Horn of Africa (Eritrea, Somalia, Ethiopia) sank near Lampedusa, a small Italian Island in the middle of the Mediterranean Sea. The recovered bodies were examined by a forensic team, and post mortem data (anthropological and odontological records, and DNA) were collected for identification. Genetic profiles based on 16 autosomal STRs were acquired from both victims and putative relatives recruited following an international call. The final genetic database included 363 victims and 43 reference persons from 36 independent families recruited until mid-2017, who were missing 35 first-degree and 6 second-degree relatives. A pairwise blind search approach was used to identify familial relationships within the victims and between victims and putative relatives. Two statistics were calculated, the Identity by State (IBS) and the Identity by Descent (IBD), the latter by using the DVI module of the FAMILIAS3 software to compute LRs and posterior probabilities. The putative identifications were confirmed in pedigree analysis using the information provided by the relatives. In selected cases, additional autosomal and lineage (Y-chromosome and mtDNA) markers were typed. Some critical points were highlighted: the lack for accurate allele and haplotype frequencies in African populations, especially for the lineage markers, and the need for a shared approach to the biostatistical interpretation of the results in DVI. In the end, 29 first-degree (parent-child and full sibs) out of 35 missing (83%), and 3 out of 6 of second-degree relatives (50%) showed a high statistical confidence for a positive identification. This study represents the first attempt to systematically deal with the genetic identification of African migrants who died in the Mediterranean Sea. The methodological and statistical approach used in this study was proved to be reliable and appropriate for future genetic identifications in other similar mass disasters.
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http://dx.doi.org/10.1016/j.fsigen.2019.102156DOI Listing
January 2020

Identification of an exhumed corpse by DNA extraction from bulb swab. A disputed parentage case report.

Sci Justice 2019 03 16;59(2):214-216. Epub 2018 Oct 16.

University of Pisa Department of Medicine- section of Legal Medicine, Pisa, Italy.

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http://dx.doi.org/10.1016/j.scijus.2018.10.001DOI Listing
March 2019

Challenges in the identification of dead migrants in the Mediterranean: The case study of the Lampedusa shipwreck of October 3rd 2013.

Forensic Sci Int 2018 Apr 6;285:121-128. Epub 2018 Feb 6.

LABANOF (Laboratorio di Antropologia e Odontologia Forense), Dipartimento di Scienze Biomediche per la Salute, Sezione di Medicina Legale, Università degli Studi di Milano, Milan, Italy. Electronic address:

Every year thousands of migrants die during the endeavour to reach the Italian coasts, making the Mediterranean the theatre of one of the greatest tragedies of mankind. Over 60% of these victims is buried unidentified: one of the reasons behind this is related to the specific difficulties and lack of strategies concerning AM and PM data collection. The present article describes how Italy is trying to face the problem of migrant identification, thanks to the collaboration between government, the Italian national police and universities. In particular, this is the first pilot study carried out to identify the victims of the second greatest tragedy of its kind off the Italian coast, near Lampedusa, on October 3rd 2013, which caused 366 victims. The present article shows the strategies conceived to collect postmortem and especially antemortem data and to compare them to identify matches, using medicolegal, anthropological, odontological and genetic approaches. Thirty-one victims out of 53 missing sought by relatives were identified (58.5%). The type and the quality of antemortem data available, generally photos and videos, pinpoints the importance of the face and the body for identification when the bodies are well preserved and how DNA analyses may at times present difficulties. In fact, critical points emerged concerning especially the lack of genetic information of the populations to which the victims belonged, the number of genetic markers needed to reach a statistical support for the identification and the need to adopt lineage markers such as mitochondrial DNA and Y-chromosome polymorphisms to identify parental relationships. This pilot study however has proven that families continue to seek their relatives and that it is possible, as well as mandatory, to identify migrant victims in spite of the difficulties in the collection of antemortem and postmortem data. In addition, considering the peculiar scenario, novel strategies for positive identification have to be defined in each field (anthropological, odontological and genetic) as well as in combination.
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http://dx.doi.org/10.1016/j.forsciint.2018.01.029DOI Listing
April 2018

Polymorphism of Opioid Receptors μ1 in Highly Hypnotizable Subjects.

Int J Clin Exp Hypn 2018 Jan-Mar;66(1):106-118

a University of Pisa , Italy.

The possible cooperation between hypnotizability-related and placebo mechanisms in pain modulation has not been consistently assessed. Here, we investigate possible genetic bases for such cooperation. The OPRM1 gene, which encodes the μ1 opioid receptor-the primary site of action for endogenous and exogenous opioids-is polymorphic in the general population for the missense mutation Asn40Asp (A118G, rs1799971). The minor allele 118G results in decreased levels of OPRM1 mRNA and protein. As a consequence, G carriers are less responsive to opioids. The aim of the study was to investigate whether hypnotizability is associated with the presence of the OPRM1 polymorphism. Forty-three high and 60 low hypnotizable individuals, as well as 162 controls, were genotyped for the A118G polymorphism of OPRM1. The frequency of the G allele was significantly higher in highs compared to both lows and controls. Findings suggest that an inefficient opioid system may be a distinctive characteristic of highs and that hypnotic assessment may predict lower responsiveness to opioids.
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http://dx.doi.org/10.1080/00207144.2018.1396128DOI Listing
February 2019

About the number of contributors to a forensic sample.

Forensic Sci Int Genet 2016 11 10;25:e18-e19. Epub 2016 Aug 10.

Norwegian University of Life Sciences, 1432, Aas, Norway.

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http://dx.doi.org/10.1016/j.fsigen.2016.08.005DOI Listing
November 2016

False deletion of the D15S986 maternal allele in a suspected case of Angelman syndrome.

Clin Chim Acta 2015 Jan 30;439:191-4. Epub 2014 Oct 30.

Department of Physiological Science, University of Pisa, Pisa, Italy. Electronic address:

Background: Angelman syndrome (AS) is a neurological disorder caused by genetic defects of the chromosome region 15q11-q13; some 70-80% of cases are due to deletions of the maternal allele, as the paternal copy is imprinted.

Design And Methods: A maternal deletion at D15S986 was reported in a suspected case of AS; this marker is located in intron 2 of the ATP10C gene, which has been implicated in the development of AS. A segment of ~830bp, including this marker and the primers used in routine genetic test, was cloned and sequenced.

Results: A single nucleotide deletion (named ATP10C*c.760+3808delA, GenBank accession number HQ856823) was detected in the middle of the forward primer, leading to allele dropout. A large European population sample (N=363) was typed, and the detected variant was characterized as a novel polymorphism, with allele frequencies of 0.882 (TAT allele) and 0.118 (T-T allele).

Conclusions: An alternative primer set was developed, for which the segregation pattern of D15S986 in the proband extended family was normal. It can replace the currently used set.
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http://dx.doi.org/10.1016/j.cca.2014.10.015DOI Listing
January 2015

Hypnotizability and Catechol-O-Methyltransferase (COMT) polymorphysms in Italians.

Front Hum Neurosci 2014 Jan 6;7:929. Epub 2014 Jan 6.

Laboratory of Cognitive and Behavioral Neurosciences, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa Pisa, Italy.

Higher brain dopamine content depending on lower activity of Catechol-O-Methyltransferase (COMT) in subjects with high hypnotizability scores (highs) has been considered responsible for their attentional characteristics. However, the results of the previous genetic studies on association between hypnotizability and the COMT single nucleotide polymorphism (SNP) rs4680 (Val(158)Met) were inconsistent. Here, we used a selective genotyping approach to re-evaluate the association between hypnotizability and COMT in the context of a two-SNP haplotype analysis, considering not only the Val(158)Met polymorphism, but also the closely located rs4818 SNP. An Italian sample of 53 highs, 49 low hypnotizable subjects (lows), and 57 controls, were genotyped for a segment of 805 bp of the COMT gene, including Val(158)Met and the closely located rs4818 SNP. Our selective genotyping approach had 97.1% power to detect the previously reported strongest association at the significance level of 5%. We found no evidence of association at the SNP, haplotype, and diplotype levels. Thus, our results challenge the dopamine-based theory of hypnosis and indirectly support recent neuropsychological and neurophysiological findings reporting the lack of any association between hypnotizability and focused attention abilities.
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http://dx.doi.org/10.3389/fnhum.2013.00929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880894PMC
January 2014

Estimated prevalence of canine Type 2 Von Willebrand disease in the Deutsch-Drahthaar (German Wirehaired Pointer) in Europe.

Res Vet Sci 2012 Dec 21;93(3):1462-6. Epub 2012 Jul 21.

Department of Veterinary Clinic, University of Pisa, Pisa, Italy.

Type 2 Von Willebrand disease (VWD) is a severe coagulopathy occurring in the Deutsch-Drahthaar dog (or German Wirehaired Pointer, DD/GWP). Recently, a causative recessive mutation has been identified, and a DNA test is now available for individual screening. The genotype distribution (clear, carrier, and affected dogs) was investigated in 1855 DD/GWP dogs using data collected by the DD DNA-VWD-Databank in several European countries. 1704 (91.8%) DD/GWP dogs were genotypically clear of the VWD mutation, 144 (7.8%) were carriers, and seven (0.4%) were affected. The estimated disease allele frequency was highest in Germany and Sweden (almost 5%), and about 1% in Denmark, Finland and Norway. The Hardy-Weinberg equilibrium was tested in the German sample, and showed no evidence of deviation.
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http://dx.doi.org/10.1016/j.rvsc.2012.06.010DOI Listing
December 2012

"PancPro" as a tool for selecting families eligible for pancreatic cancer screening: an Italian study of incident cases.

Dig Liver Dis 2012 Jul 26;44(7):585-8. Epub 2012 Jan 26.

Gastroenterology Unit, Pisa University Hospital, Italy.

Background: PancPRO is a computer program that estimates the risk of pancreatic cancer for asymptomatic individuals based on a genetic model of susceptibility and the familial incidence of cancer.

Aim: To evaluate the distribution of the familial risk in a series of incident cases of pancreatic adenocarcinoma.

Materials And Methods: The lifetime risk of pancreatic cancer was calculated by PancPro for a hypothetical 40-year-old son of 570 consecutive probands with pancreatic cancer.

Results: The 570 risk values were included between 1% and 13%. The distribution was bimodal, with the antimode located at risk=7.5%. Considering a 10-fold risk over the general population as a threshold for including a subject in a surveillance program, 19 families (3.3%) would be selected, totalling 92 first-degree relatives with age >40 years.

Conclusions: PancPro is a valid instrument to rank families based on risk of pancreatic cancer.
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http://dx.doi.org/10.1016/j.dld.2011.12.019DOI Listing
July 2012

Association of donor-specific microchimerism with graft dysfunction in kidney transplant patients.

Transpl Immunol 2012 Mar 12;26(2-3):151-5. Epub 2011 Nov 12.

Immunohematology Unit, Cisanello Hospital, Pisa, Italy.

The biological significance of donor-specific microchimerism (DSM) in solid organ transplantation is unresolved. It has been reported both as a favourable feature, which may facilitate induction and maintenance of tolerance, and as a sign of graft-vs-host disease. Here, we applied a quantitative real-time PCR assay (qRT-PCR) to a selected series of kidney transplant recipients to measure the level of microchimerism in relation to allograft function and survival. DSM level was assessed by scoring the HLA-DRB1 locus in 54 patients (42 males, 12 females) with more than 2 years of follow-up after transplantation; 38 patients were considered to have stable renal function (SRF) and 16 had allograft dysfunction (AD). Among patients with AD, 12 (75%) showed detectable level of microchimerism, compared to 11 (29%) SRF patients (Odds Ratio 7.36, 95% CI 1.7-35.2; p<0.01). In addition, AD patients showed a higher mean donor genome equivalents (6.5×10(-5) vs. 2.4×10(-5); p<0.001). SRF patients were re-evaluated two years later; 2 out of 27 DSM negative vs. 2 out of 11 DSM positive had lost their transplanted organ. In conclusion, qRT-PCR applied to peripheral blood shows significant association between DSM and allograft dysfunction in kidney transplant patients.
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http://dx.doi.org/10.1016/j.trim.2011.11.004DOI Listing
March 2012

Fleece variation in alpaca (Vicugna pacos): a two-locus model for the Suri/Huacaya phenotype.

BMC Genet 2010 Jul 20;11:70. Epub 2010 Jul 20.

Department of Physiological Sciences, University of Pisa, Via San Zeno 31, 56123 Pisa, Italy.

Background: Genetic improvement of fibre-producing animal species has often induced transition from double coated to single coated fleece, accompanied by dramatic changes in skin follicles and hair composition, likely implying variation at multiple loci. Huacaya, the more common fleece phenotype in alpaca (Vicugna pacos), is characterized by a thick dense coat growing perpendicularly from the body, whereas the alternative rare and more prized single-coated Suri phenotype is distinguished by long silky fibre that grows parallel to the body and hangs in separate, distinctive pencil locks. A single-locus genetic model has been proposed for the Suri-Huacaya phenotype, where Huacaya is recessive.

Results: Two reciprocal experimental test-crosses (Suri x Huacaya) were carried out, involving a total of 17 unrelated males and 149 unrelated females. An additional dataset of 587 offspring of Suri x Suri crosses was analyzed. Segregation ratios, population genotype frequencies, and/or recombination fraction under different genetic models were estimated by maximum likelihood. The single locus model for the Suri/Huacaya phenotype was rejected. In addition, we present two unexpected observations: 1) a large proportion (about 3/4) of the Suri animals are segregating (with at least one Huacaya offspring), even in breeding conditions where the Huacaya trait would have been almost eliminated; 2) a model with two different values of the segregation ratio fit the data significantly better than a model with a single parameter.

Conclusions: The data support a genetic model in which two linked loci must simultaneously be homozygous for recessive alleles in order to produce the Huacaya phenotype. The estimated recombination rate between these loci was 0.099 (95% C.L. = 0.029-0.204). Our genetic analysis may be useful for other species whose breeding system produces mainly half-sib families.
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http://dx.doi.org/10.1186/1471-2156-11-70DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2914767PMC
July 2010

Familial pancreatic cancer in Italy. Risk assessment, screening programs and clinical approach: a position paper from the Italian Registry.

Dig Liver Dis 2010 Sep 2;42(9):597-605. Epub 2010 Jun 2.

Division of General and Transplant Surgery, Pisa University Hospital, Via Paradisa 2, 56124 Cisanello, Pisa, Italy.

In Italy, pancreatic cancer is the fifth leading cause of tumor related death with about 7000 new cases per year and a mortality rate of 95%. In a recent prospective epidemiological study on the Italian population, a family history was found in about 10% of patients suffering from a ductal adenocarcinoma of the pancreas (PDAC). A position paper from the Italian Registry for Familial Pancreatic Cancer was made to manage these high-risk individuals. Even though in the majority of high-risk individuals a genetic test to identify familial predisposition is not available, a screening protocol seems to be reasonable for subjects who have a >10-fold greater risk for the development of PDAC. However this kind of screening should be included in clinical trials, performed in centers with high expertise in pancreatic disease, using the least aggressive diagnostic modalities.
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http://dx.doi.org/10.1016/j.dld.2010.04.016DOI Listing
September 2010

Promoter polymorphisms of the NOS3 gene are associated with hypnotizability-dependent vascular response to nociceptive stimulation.

Neurosci Lett 2009 Dec 22;467(3):252-5. Epub 2009 Oct 22.

Dept of Physiological Sciences, University of Pisa, Via San Zeno 31, 56127 Pisa, Italy.

Hypnotizability is associated with a few physiological characteristics also in the normal awake state. Differences in flow-mediated dilation (FMD) have been observed in subjects with high (Highs) or low (Lows) hypnotizability during nociceptive stimulation. FMD is largely due to the nitric oxide (NO) produced by vascular endothelium through the activity of NO synthase (eNOS). Endothelial NOS is encoded by the NOS3 locus. Aim of this pilot study was to investigate the association between genetic polymorphisms of NOS3 involved in NO blood levels and hypnotizability. Nine single nucleotide polymorphisms (SNPs) of the NOS3 gene were analyzed in the DNA of 24 Highs, 22 Lows, and 61 newborns. Two SNPs, rs1800783 (-1474 T/A) and rs2070744 (-786 T/C), located in the upstream and promoter region of the gene, respectively, showed significant differences between Highs and Lows in allele frequency. Haplotype analysis showed that the newborns were in linkage equilibrium for these SNPs, whereas both Highs and Lows showed linkage disequilibrium. The A-C haplotype (associated with lower NO availability in the general population) was more frequent in Highs, and the T-T haplotype was more frequent in Lows. Thus, the lower FMD reduction observed in Highs during nociceptive stimulation, which is indicative of higher NO availability, should be due to greater efficacy of shear stress-related transcriptional factors and/or to lower effects of NOS inhibitory controls. A consequent theoretical proposal concerns the possible role of NO in the brain vessels where, in stimulation conditions, NO diffusion to the extracellular compartment might be involved in hypnotic responding.
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http://dx.doi.org/10.1016/j.neulet.2009.10.056DOI Listing
December 2009

MDR1 diplotypes as prognostic markers in multiple myeloma.

Pharmacogenet Genomics 2008 May;18(5):383-9

Department of Biology, Transplants and Advanced Technologies, Section of Hematology, Pisa University, Pisa, Italy.

Objective: The aim of this study was to evaluate the effect of diplotypes of MDR1 polymorphisms at positions 2677 and 3435 on the clinical outcome of multiple myeloma, in terms of response to the therapy and overall survival (OS).

Methods: G2677T/A SNP was analysed by RFLP-PCR assay on 110 patients, treated with dexamethasone, doxorubicin (adryamicin) and vincristine regimen, followed by autologous stem cell transplantation.

Results: Treatment efficacy was not related to G2677T/A SNP, whereas the OS of G/G carriers was significantly shorter than that of T/T or G/T patients. Similar results were previously reported for MDR1 C3435T polymorphism. Given that these two single nucleotide polymorphisms are in strong linkage disequilibrium, we analyzed the effects of the most frequent haplo/diplotypes and the survival probability was lower for GC/GC patients (55%) than for GC/TT and TT/TT carriers (>80%; log-rank test, P=0.03). Interestingly, the effect of MDR1 diplotype on the OS seems to be confined to autologous stem cell transplantation nonresponders.

Conclusion: These results support the hypothesis that genetic variability of MDR1 should be considered as an important factor that influences the clinical outcome of multiple myeloma.
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http://dx.doi.org/10.1097/FPC.0b013e3282f82297DOI Listing
May 2008

Haplotype analysis of the H63D, IVS2+4t/c, and C282Y polymorphisms of the HFE gene reveals rare events of intragenic recombination.

Eur J Haematol 2008 Apr 21;80(4):341-5. Epub 2007 Dec 21.

U.O. Immunoematologia 2-Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.

Objective: Two missense mutations of the HFE gene, one (C282Y) being a major gene for hereditary hemochromatosis and the other (H63D) playing a minor role in this disease, are carried by different haplotypes. Among other sequence variants of HFE, IVS2+4t/c polymorphism has been reported as a possible splicing mutation or risk modifier. Our aims were to identify sequence variants possibly associated with iron overload in our population, to study the intragenic haplotypes of the HFE gene, and to evaluate the role of IVS2+4t/c in hyperferritinemia.

Methods: We screened by direct sequencing the coding sequence and intron-exon boundaries of HFE in 265 patients with hyperferritinemia and 185 subjects from the general population.

Results: Linkage disequilibrium between the three pairs of polymorphic sites was complete between H63D and C282Y, whereas all four gametic types were present for both the H63D-IVS2+4t/c and the IVS2+4t/c-C282Y site pairs. The data supported a model in which the IVS2+4t/c polymorphism was ancestral, the D(63) mutation occurred on the t chromosome, and the Y(282) mutation occurred on the c chromosome; after the population spread of both mutations, intragenic recombination occurred on both sides of the t/c polymorphism, generating the rare haplotypes D(63)-c(IVS2+4)-C(282) and H(63)-t(IVS2+4)-Y(282).

Conclusions: The IVS2+4c/t is a neutral polymorphism with regard to risk of iron overload. The presence of recombinant haplotypes on both its sides suggests a considerable evolutionary age of the two main risk alleles.
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http://dx.doi.org/10.1111/j.1600-0609.2007.01025.xDOI Listing
April 2008

Cancer risk among the relatives of patients with pancreatic ductal adenocarcinoma.

Pancreatology 2007 1;7(5-6):459-69. Epub 2007 Oct 1.

Regional Referral Center for Pancreatic Diseases Treatment, University of Pisa, Pisa, Italy.

Background/aims: Pancreatic cancer is a leading cause of cancer-related death; the most consistently identified risk factors are smoking and family history. Our aims were to examine familial aggregations of pancreas and other cancers, and to determine the relative risk of the family members.

Methods: We prospectively collected data on the families of patients presenting with pancreatic ductal adenocarcinoma. Smoking habits and alcohol consumption of the probands were compared with the available statistics on the Italian population. Mortality from cancer was investigated in first-degree relatives, and age-dependent risks of dying from pancreatic cancer and other tumors were compared with background population levels.

Results: Data for 570 families were collected, including 9,204 relatives. Probands were 3- to 5-fold more often heavy smokers than the general population, and 9.3% of them reported a positive family history of pancreatic cancer. In first-degree relatives, only mortality from pancreatic cancer was significantly increased (relative risk at age 85 years = 2.7). Lifetime risk of dying of pancreas cancer was 4.1% for the relatives of all probands, and was 7.2% for the relatives of probands who developed disease before 60 years of age.

Conclusions: The data suggest that genetic susceptibility to pancreatic cancer may be attributable, in addition to BRCA2, to moderate- to low-penetrance gene(s).
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http://dx.doi.org/10.1159/000108963DOI Listing
November 2007

Genotype probabilities of pairs of individuals for X-chromosome markers.

Transfusion 2007 Jul;47(7):1276-80

Unit of Legal Medicine, School of Medicine, University of Pisa, Italy.

Background: The usual set of autosomal markers (A-STRs) available in commercial kits is often insufficient to discriminate between close relationships when only two subjects are available for analysis. X-chromosome markers (X-STRs) provide higher statistical power in special cases.

Study Design And Methods: Formulas are derived for the probabilities of all possible genotype pairs for X-STRs of any sex combination for seven common relationships. The power of exclusion (PE) of X-STRs in parentage analysis is compared with that of A-STRs of equivalent distribution of allele frequency.

Results: Seventy-three equations were obtained, from which the likelihood ratio of any two alternative hypotheses about the relationship between two individuals can be obtained by division and simplification. For father-daughter and mother-son duos, the PE of X-STRs is almost twice the corresponding value of A-STRs for moderately low values of heterozygosity (0.6-0.75); for alleged pairs of sisters and pairs of half-sisters the PE is equivalent to that of A-STRs in parent-child duos. Considering four real unlinked X-STRs, the cumulative PE for father-daughter and mother-son duos was 99 percent, compared with 94 percent if they were autosomal.

Conclusions: X-STRs can substantially increase the discrimination capacity of standard A-STRs in parentage analyses involving pairs of individuals. Up to four unlinked X-STRs may be treated as independent loci. When linked loci are included, computer programs that calculate pedigree likelihoods can be used.
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http://dx.doi.org/10.1111/j.1537-2995.2007.01270.xDOI Listing
July 2007

Haplotypic structure of the X chromosome in the COGA population sample and the quality of its reconstruction by extant software packages.

BMC Genet 2005 Dec 30;6 Suppl 1:S77. Epub 2005 Dec 30.

Center of Statistical Genetics, c/o Centro Retrovirus, SS Abetone e Brennero 2, 56127 Pisa, Italy.

Background: The haplotypes of the X chromosome are accessible to direct count in males, whereas the diplotypes of the females may be inferred knowing the haplotype of their sons or fathers. Here, we investigated: 1) the possible large-scale haplotypic structure of the X chromosome in a Caucasian population sample, given the single-nucleotide polymorphism (SNP) maps and genotypes provided by Illumina and Affimetrix for Genetic Analysis Workshop 14, and, 2) the performances of widely used programs in reconstructing haplotypes from population genotypic data, given their known distribution in a sample of unrelated individuals.

Results: All possible unrelated mother-son pairs of Caucasian ancestry (N = 104) were selected from the 143 families of the Collaborative Study on the Genetics of Alcoholism pedigree files, and the diplotypes of the mothers were inferred from the X chromosomes of their sons. The marker set included 313 SNPs at an average density of 0.47 Mb. Linkage disequilibrium between pairs of markers was computed by the parameter D', whereas for measuring multilocus disequilibrium, we developed here an index called D*, and applied it to all possible sliding windows of 5 markers each. Results showed a complex pattern of haplotypic structure, with regions of low linkage disequilibrium separated by regions of high values of D*. The following programs were evaluated for their accuracy in inferring population haplotype frequencies: 1) ARLEQUIN 2.001; 2) PHASE 2.1.1; 3) SNPHAP 1.1; 4) HAPLOBLOCK 1.2; 5) HAPLOTYPER 1.0. Performances were evaluated by Pearson correlation (r) coefficient between the true and the inferred distribution of haplotype frequencies.

Conclusion: The SNP haplotypic structure of the X chromosome is complex, with regions of high haplotype conservation interspersed among regions of higher haplotype diversity. All the tested programs were accurate (r = 1) in reconstructing the distribution of haplotype frequencies in case of high D* values. However, only the program PHASE realized a high correlation coefficient (r > 0.7) in conditions of low linkage disequilibrium.
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http://dx.doi.org/10.1186/1471-2156-6-S1-S77DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1866704PMC
December 2005

Validation of a large Italian Database of 15 STR loci.

Forensic Sci Int 2006 Jan 22;156(2-3):266-8. Epub 2005 Apr 22.

Center of Statistical Genetics, SS Abetone e Brennero 2, 56127 Pisa, Italy.

Results from a collaborative exercise with proficiency testing conducted by 20 Italian laboratories on the 15 loci included in the Identifiler kit were analyzed by allele sharing methods and by standard population genetics tests. The validated database, including about 1500 subjects, was merged with that of a previous exercise conducted on nine loci, and the resulting allele frequencies, subdivided by Italian region, were published on-line.
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http://dx.doi.org/10.1016/j.forsciint.2005.03.001DOI Listing
January 2006

Relationships between total plasma load of torquetenovirus (TTV) and TTV genogroups carried.

J Clin Microbiol 2005 Sep;43(9):4807-10

Virology Section and Retrovirus Center, Department of Experimental Pathology, University of Pisa, Italy.

In 239 torquetenovirus-positive people, multiple-genogroup infections were common and associated with higher viral loads than would be expected from simple additive effects. The latter observation was restricted to the infections which included both genogroups 1 and 3, pointing to the possible existence of some kind of infection facilitation between these genogroups.
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http://dx.doi.org/10.1128/JCM.43.9.4807-4810.2005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1234078PMC
September 2005

Development of a heptaplex PCR system to analyse X-chromosome STR loci from five Italian population samples. A collaborative study.

Forensic Sci Int 2005 Oct;153(2-3):231-6

Department of Medicine and Public Health, Section of Legal Medicine, University of Bologna, Via Irnerio 49, 40126 Bologna, Italy.

Many X-chromosome short tandem repeats (X-STRs) have been validated for forensic use even if further studies are needed on allele frequencies and mutation rates to evaluate the extent of polymorphism in different populations and to establish reference databases useful for forensic applications and for anthropological studies. A single multiplex reaction of seven X-STRs, which includes the DXS6789, HUMARA, DXS10011, DXS7423, HPRTB, DXS6807, DXS101 loci, is presented and their allele frequency distribution in a large population sample including 556 subjects (268 females and 288 males) analysed by five forensic laboratories of Central and Northern Italy is shown. Our results demonstrate the feasibility of a single amplification/detection reaction involving seven markers of the X chromosome, which can be fruitfully used in complex kinship analysis.
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http://dx.doi.org/10.1016/j.forsciint.2005.05.013DOI Listing
October 2005

Genetics of pancreatic cancer: where are we now? Where are we going?

JOP 2005 Jan 13;6(1 Suppl):60-7. Epub 2005 Jan 13.

Division of General and Transplant Surgery, Regional Referral Center for Pancreatic Diseases Treatment, University of Pisa. Pisa, Italy.

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January 2005

Penetrances of breast and ovarian cancer in a large series of families tested for BRCA1/2 mutations.

Eur J Hum Genet 2004 Nov;12(11):899-906

Department of Oncology, Transplants and New Technologies in Medicine, Section of Pathology, University of Pisa, Pisa, Italy.

Accurate estimates of breast and ovarian cancer penetrance in BRCA1/2 mutation carriers are crucial in genetic counseling. Estimation is difficult because of the low frequency of mutated alleles and the often-uncertain mechanisms of family ascertainment. We estimated the penetrances of breast and ovarian cancers in carriers of BRCA1/2 mutations by maximizing the retrospective likelihood of the genetic model, given the observed test results, in 568 Italian families screened for germline mutations. The software BRCAPRO was used as a probability calculation tool in a Markov Chain Monte Carlo approach. Breast cancer penetrances were 27% (95% CI 20-34%) at age 50 years and 39% (27-52%) at age 70 in BRCA1 carriers, and 26% (0.18-0.34%) at age 50 and 44% (29-58%) at age 70 in BRCA2 carriers, and ovarian cancer penetrances were 14% (7-22%) at age 50 and 43% (21-66%) at age 70 in BRCA1 carriers and 3% (0-7%) at age 50 and 15% (4-26%) at age 70 in BRCA2 carriers. The new model gave a better fit than the current default in BRCAPRO, the likelihood being 70 log units greater; in addition, the observed numbers of mutations in families stratified by gene and by cancer profile were not significantly different from those expected. Our new penetrance functions are appropriate for predicting breast cancer risk, and for determining the probability of carrying BRCA1/2 mutations, in people who are presently referred to genetic counseling in Italy. Our approach could lead to country-customized versions of the BRCAPRO software by providing appropriate population-specific estimates.
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http://dx.doi.org/10.1038/sj.ejhg.5201256DOI Listing
November 2004

Correlation between Torque tenovirus infection and serum levels of eosinophil cationic protein in children hospitalized for acute respiratory diseases.

J Infect Dis 2004 Sep 23;190(5):971-4. Epub 2004 Jul 23.

Virology Section and Retrovirus Center, Department of Experimental Pathology, University of Pisa, Italy.

Children with bronchopneumonia have considerably higher Torque tenovirus (TTV) loads than do children with milder acute respiratory diseases (ARDs). Moreover, in children with ARDs, high TTV loads correlate with low percentages of circulating CD3+ and CD4+ T cells and with elevated percentages of B cells, suggesting that TTV might be immunomodulatory. Here, we show that, in children with ARDs, the presence of TTV and TTV load correlate with concentrations of serum eosinophil cationic protein. The possible mechanisms whereby TTV infection might lead to augmented activity of eosinophils and the implications for pathogenesis are discussed.
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http://dx.doi.org/10.1086/423143DOI Listing
September 2004

Haplotype analysis of BRCA1 gene reveals a new gene rearrangement: characterization of a 19.9 KBP deletion.

Eur J Hum Genet 2004 Sep;12(9):775-7

Section of Oncogenetics, Division of Surgical, Molecular and Ultrastructural Pathology, Department of Oncology, Transplants and New Technologies in Medicine, University of Pisa and University Hospital of Pisa, Italy.

Germ-line mutations in the BRCA1 gene cause hereditary predisposition to breast and ovarian cancer. BRCA1 and BRCA2 mutations account for about 40% of high-risk families. Mutation-screening methods generally focus on genomic DNA and are usually PCR based; they enable the detection of sequence alterations such as point mutations and small deletions and insertions. However, they do not allow the detection of partial or entire exon(s) loss, because the presence of the homologous allele results in a positive PCR signal, giving rise to a false-negative result. Identification of unusual haplotypes in patient samples by an expectation maximization algorithm has recently been suggested as a method for identifying hemizygous regions caused by large intragenic deletions. Using a similar approach, we identified a novel BRCA1 genomic rearrangement in a breast/ovarian cancer family negative at the first mutation screening; we detected a deletion encompassing exons 14-19, probably due to replication slippage between Alu sequences.
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http://dx.doi.org/10.1038/sj.ejhg.5201223DOI Listing
September 2004

Population data of four X-chromosome markers in Tuscany, and their use in a deficiency paternity case.

Forensic Sci Int 2003 Nov;137(2-3):215-6

Unit of Legal Medicine, School of Medicine, University of Pisa, Via Roma, Pisa, Italy.

Four X-chromosome markers (DXS101, HPRTB, DXS8377, and STRX-1) were typed in a population sample from Tuscany, Italy, using a single amplification reaction. Resolution of a deficiency paternity case involving two women (either they were half-sisters or non-relatives) was made possible by typing these marker in addition to 16 conventional autosomal markers.
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http://dx.doi.org/10.1016/j.forsciint.2003.07.004DOI Listing
November 2003

Evolution of two amino acid positions governing broad neutralization resistance in a strain of feline immunodeficiency virus over 7 years of persistence in cats.

Clin Diagn Lab Immunol 2003 Nov;10(6):1109-16

Retrovirus Center and Virology Section, Department of Experimental Pathology, University of Pisa, Pisa, Italy.

Fresh isolates of lentiviruses are characterized by an outstanding resistance to antibody-mediated neutralization. By investigating the changes that occurred in a neutralization-sensitive tissue culture-adapted strain of feline immunodeficiency virus after it was reinoculated into cats, a previous study had identified two amino acid positions of the surface glycoprotein (residues 481 and 557) which govern broad neutralization resistance (BNR) in this virus. By extending the follow-up of six independently evolving in vivo variants of such virus for up to 92 months, we now show that the changes at the two BNR-governing positions not only were remarkably stereotyped but also became fixed in an ordered sequential fashion with the duration of in vivo infection. In one variant, the two positions were also seen to slowly alternate at determining BNR. Evidence that evolution at the BNR-governing positions was accompanied, and possibly driven, by changes in the antigenic makeup of the viral surface brought about by the mutations at such positions is also presented.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC262447PMC
http://dx.doi.org/10.1128/cdli.10.6.1109-1116.2003DOI Listing
November 2003

Different expressivity of BRCA1 and BRCA2: analysis of 179 Italian pedigrees with identified mutation.

Breast Cancer Res Treat 2003 Sep;81(1):71-9

Section of Oncogenetics, Division of Surgical, Molecular and Ultrastructural Pathology, Department of Oncology, University of Pisa, Pisa, Italy.

Mutations in BRCA1 and BRCA2 show different expressivity with respect to cancer risk, and allelic heterogeneity may be present in both genes. We collected 179 pedigrees with identified germline mutation (104 BRCA1 and 75 BRCA2), ascertained in six collaborating centers of the Italian Consortium for Hereditary Breast and Ovarian Cancer. Significant heterogeneity was detected for several variables, and a logistic regression model including age of diagnosis in the proband, presence of ovarian cancer in the family, presence of prostate or pancreatic cancer in the family, and presence of male breast cancer in the family proved to be effective in predicting the presence of a mutation in a gene rather than the other. Excess of familial aggregation of both breast and ovarian cancer was observed in both genes. Proportion of ovarian cancer was increased in the 5' portion of BRCA1, and presence of prostate or pancreatic cancer in a family was correlated with presence of ovarian cancer in BRCA2.
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http://dx.doi.org/10.1023/a:1025428807472DOI Listing
September 2003