'COV'COP' allows to detect CNVs responsible for inherited diseases among amplicons sequencing data.

SUMMARY: In order to help molecular geneticists to rapidly identify CNVs responsible for inherited diseases among amplicons sequencing data generated by NGS, we designed a user-friendly tool ' Cov'Cop '. Using the run's coverage file provided by the sequencer, Cov'Cop simultaneously analyzes all the patients of the run using a two-stage algorithm containing correction and normalization levels and provides an easily understandable output, showing with various colors, potentially deleted and duplicated amplicons. AVAILABILITY AND IMPLEMENTATION: https://git.unilim.fr/merilp02/CovCop. CONTACT: asliabaldini@unilim.fr. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Association between completed suicide and bipolar disorder: A systematic review of the literature.

BACKGROUND: Completed suicide is a major cause of death in bipolar disorder (BD) patients. OBJECTIVE: The aim of this paper is to provide an overall review of the existing literature of completed suicide in BD patients, including clinical and genetic data DATA SOURCES: We performed a systematic review of English and non-English articles published on MEDLINE/PubMed, PsycInfo and Cochrane database (1970-2017). Additional studies were identified by contacting clinical experts, searching bibliographies, major textbooks and website of World Health Organization. Initially we did a broad search for the association of bipolar disorder and suicide and we were narrowing the search in terms included "bipolar disorder" and "completed suicide". STUDY SELECTION: Inclusion criteria were articles about completed suicide in patients with BD. Articles exclusively focusing on suicide attempts and suicidal behaviour have been excluded. We used PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) consensus for drafting this systematic review. RESULTS: The initial search generated 2806 articles and a total of 61 meeting our inclusion criteria. We reviewed epidemiological data, genetic factors, risk factors and treatment of completed suicide in BD. Suicide rates in BD vary between studies but our analyses show that they are approximately 20-30-fold greater than in general population. The highest risk of successful suicide was observed in BD-II subjects. The heritability of completed suicide is about 40% and some genes related to major neurotransmitter systems have been associated with suicide. Lithium is the only treatment that has shown anti-suicide potential. LIMITATIONS: The most important limitation of the present review is the limited existing literature on completed suicide in BD. CONCLUSIONS: BD patients are at high risk for suicide. It is possible to identify some factors related to completed suicide, such as early onset, family history of suicide among first-degree relatives, previous attempted suicides, comorbidities and treatment. However it is necessary to promote research on this serious health problem.

Allele frequencies of the 15 AmpF/Str Identifiler loci in the population of Metztitlán (Estado de Hidalgo), México.

The 15 AmpF/STR Identifiler loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA) were analyzed in the sample of 180 unrelated autochthonous healthy adults born in Meztitlán City from the valley of Metztitlán (Estado de Hidalgo, México). The agreement with Hardy-Weinberg equilibrium was confirmed for all loci. From the forensic point of view, the heterozygosity value, power of discrimination and the a priori chance of exclusion were calculated.

Excretion of hexachlorobenzene and metabolites in feces in a highly exposed human population.

A set of 53 individuals from a population highly exposed to airborne hexachlorobenzene (HCB) were selected to study the elimination kinetics of this chemical in humans. The volunteers provided blood, 24-hr urine, and feces samples for analysis of HCB and metabolites. The serum HCB concentrations ranged from 2.4 to 1,485 ng/mL (mean +/- SD, 124 +/- 278), confirming that this human population has the highest HCB blood levels ever reported. All analyzed feces samples contained unchanged HCB (range, 11-3,025 ng/g dry weight; mean +/- SD, 395 +/- 629). The HCB concentration in feces strongly correlated with HCB in serum (r = 0.85; p < 0.001), suggesting an equilibrium in feces/serum that is compatible with a main pulmonary entrance of the chemical and low intestinal excretion of nonabsorbed foodborne HCB. The equilibrium is also compatible with a nonbiliary passive transfer of the chemical to the intestinal lumen. Two HCB main metabolites, pentachlorophenol (PCP) and pentachlorobenzenethiol (PCBT), were detected in 51% and 54% of feces samples, respectively. All urine samples contained PCP and PCBT, confirming the conclusions of a previous study [Environ Health Perspect 105:78-83 (1997)]. The comparison between feces and urine showed that whereas daily urinary elimination of metabolites may account for 3% of total HCB in blood, intestinal excretion of unchanged HCB may account for about 6%, thus showing the importance of metabolism in the overall elimination of HCB. The elimination of HCB and metabolites by both routes, however, appears to be very small (< 0.05%/day) as compared to the estimated HCB adipose depots. Features of HCB kinetics that we present in this study, i.e., nonsaturated intestinal elimination of HCB and excretion in feces and urine of inert glutathione derivatives, may explain, in part, the absence of porphyria cutanea in this human population heavily exposed to HCB.

Metabolism of hexachlorobenzene in humans: association between serum levels and urinary metabolites in a highly exposed population.

Serum and urine from 100 subjects of a general population highly exposed to airborne hexachlorobenzene (HCB) were analyzed to obtain new insights into the metabolism of this ubiquitous compound. HCB was detected in all serum samples with concentrations ranging between 1.1 and 953 ng/ml. The major known metabolites of HCB were investigated in urine collected over 24 hr. Pentachlorophenol (PCP) was detected in all urines with values ranging between 0.58 and 13.9 micrograms excreted in 24 hr [mean +/- standard deviation (SD), 2.52 +/- 2.05; geometric mean, 2.05]. A sulfur derivative that, after hydrolysis, yielded pentachlorobenzenethiol (PCBT) could also be identified and quantified in all the urines with values ranging between 0.18 and 84.0 micrograms of PCBT excreted in 24 hr (mean +/- SD, 3.47 +/- 10.8; geometric mean, 1.39). The sulfur derivative assessed as PCBT appeared to be the main metabolite, with urinary concentrations surpassing those of PCP in the subjects with higher HCB accumulation (HCB in serum > 32 ng/ml). PCBT concentration in urine collected over 24 hr showed a very strong association with HCB concentration in serum; the association was stronger in males than in females. An increase of 1 ng/ml of HCB in serum led to an increase of 2.12 micrograms of PCBT excreted in urine collected over 24 hr in males (95% CI, 1.82-2.44) and to an increase of 0.67 microgram of PCBT in females (CI, 0.33-1.09). A weaker association was found between PCP in urine and HCB in serum, which was only statistically significant in males (an increase of 1 ng/ml of HCB in serum led to an increase of 0.63 microgram of PCP excreted in urine collected over 24 hr; (CI, 0.34-0.95). These results show that the formation of the cysteine conjugate is a quantitatively more important metabolic pathway in humans than the formation of PCP. Moreover, the association found suggests that PCBT is a good urinary marker of HCB internal dose and glutathione-mediated metabolism.

Analysis of biological phenotypes from 42 patients with inherited factor VII deficiency: can biological tests predict the bleeding risk?

BACKGROUND AND OBJECTIVES: Inherited factor VII (FVII) deficiency is a rare bleeding disorder characterized by a poor relationship between reported FVII clotting activity (FVII:C) and bleeding tendency. Our study was aimed at defining biological parameters that are possibly predictive for bleeding risk in this condition. DESIGN AND METHODS: Forty-two FVII-deficient patients (FVII:C <30%) were classified into two opposite clinical groups defined as severe and non-or-mild bleeders. For each patient, plasma samples were collected and then investigated for FVII:C (using a sensitive method and human recombinant thromboplastin as the reagent), FVII antigen, activated FVII coagulant activity (FVIIa:C) and the free-form of tissue factor pathway inhibitor. RESULTS: None of these tests could be used as highly accurate predictors of bleeding. Nevertheless, both FVII:C and FVIIa:C differed significantly between the two clinical groups. Using ROC-curve analysis, two critical values of 8% and 3mIU/mL for FVII:C and FVIIa:C, respectively, could be proposed to discriminate between severe bleeders and non-or-mild bleeders. INTERPRETATION AND CONCLUSIONS: A highly accurate diagnostic test for predicting bleeding tendency in inherited FVII deficiency still eludes definition, highlighting the fact that factors other than FVII itself interfere with the expression of bleeding phenotypes in this condition. Nevertheless, potential critical values using sensitive FVII:C and FVIIa:C methods may be useful in clinical laboratories for FVII-deficient patients. Those patients with FVII:C levels higher than 8% FVII:C or FVIIa:C higher than 3 mIU/mL, with no other hemostatic defect, seem to have a minimal risk of severe bleeding. Extended clinical studies are needed to support these findings.

Accumulation of hexachlorobenzene in humans: a long standing risk.

1. Hexachlorobenzene (HCB) internal dose in the general population of Barcelona (Spain) was estimated after new indications of the carcinogenicity of this chemical in humans were recently reported. Hospital blood bank facilities and randomly selected volunteers were used for HCB analyses in serum (n = 100) and cerumen (n = 25). Other main organochlorine residues often found in human tissues and blood (pp DDE, beta-HCH,) were also determined. 2. HCB serum levels currently found (Range 0.7-19.7 ng Ml-1; X +/- s.d.: 4.13 +/- 3.61; GM: 3.05) were compared to those found in a similar survey made in 1986 on the same population. The serum HCB levels showed a significant decrease (P < 0.001) when compared to the former results and correlated with age (P < 0.001) suggesting a progressive preponderance of a stable blood-adipose equilibrium with fewer variations due to recent and variable intake of the chemical. 3. Cerumen analyses revealed detectable concentrations of HCB in all samples (Range: 160-4790 ng g-1 in extractable lipid basis) and confirmed the suitability of this matrix to assess the body burden of residues accumulated in adipose and lipid-rich tissues. The set of results shows that, although HCB exposure has been reduced, the overall population under study still accumulates significant amounts of this possible carcinogen.

DNA paternity tests in Spain without the mother's consent: the legal responsibility of the laboratories.

It is technically feasible to perform paternity diagnosis testing solely involving an alleged father and his descendent. However, there are serious legal and ethical problems for forensic genetics laboratories when it comes to paternity testing cases for investigating the alleged father-child relationship if the biological mother has not given consent to access her genetic information. Based on the Spanish Constitution, the new Code of Ethics of the Spanish Medical Association includes several articles on studies about genetic information and their acceptance by all the individuals involved. This problem is greater when the child is a minor, mentally incapacitated or psychologically incapable, because current Spanish law requires informed consent from legal representatives, but the law does not typify what happens when one parent gives consent (the putative father) and the other parent (the mother) does not agree. The aim of this study is to put forward legal solutions to avoid potential legal problems.

Data for Y-chromosome haplotypes in Fang and Bubi populations from Bioko (Equatorial Guinea).

Haplotype frequencies for 16 Y-chromosomal short tandem repeat (DYS456, DYS389I, DYS390, DYS389II, DYS458, DYS19, DYS385a/b, DYS393, DYS391, DYS439, DYS635, DYS392, Y GATA H4, DYS437, DYS438 and DYS448) loci, included in the AmpFLSTR Yfiler PCR Amplification Kit, were analysed in 110 Fang and 133 Bubi individuals from Bioko Island, Equatorial Guinea. The diversity was higher in Fang population, probably since they were originally from the mainland, with which they maintain tribal village and family links, and to which they travel frequently. Comparisons were made with previously published haplotype data on European and African populations, and significant differences were found between them.

Haplotype frequencies of 16 Y-chromosome STR loci in the Barcelona metropolitan area population using Y-Filer kit.

Haplotype frequencies for 16 Y-chromosomal short tandem repeat (STR) loci, included in the Y-Filer kit, were determined in 247 unrelated healthy individuals from the Barcelona metropolitan area (Catalonia, NE Spain). After PCR amplification and denaturing PAGE electrophoresis, DYS456, DYS389I, DYS390, DYS389II, DYS458, DYS19, DYS385a/b, DYS393, DYS391, DYS439, DYS635, DYS392, Y GATA H4.1, DYS437, DYS438 and DYS448 loci were typed. The aim of this study is to evaluate the performance in our population of the 16 loci of the Y-chromosome present in the new Y-Filer commercial identification kit, and acquire haplotype frequencies for mathematic processing of the forensic diagnosis in our geographical working area. In this sample, all haplotypes were unique. From the forensic point of view, the combined polymorphisms of the Y-Filer kit provide a high diagnostic efficiency.

The Fang population of Equatorial Guinea characterised by 15 STR-PCR polymorphisms.

Allele frequencies for 15 STR loci (D8S1179, D21S11, D7S820, CSF1PO, D19S433, HUMVWA31A, HUMTPOX, D18S51, D3S1358, HUMTHO1, D13S317, D16S539, D2S1338, D5S818 and HUMFGA) were analysed in the Fang population of Bioko Island, Equatorial Guinea. No deviation from Hardy-Weinberg equilibrium was found for all loci. Statistical parameters demonstrated the forensic utility of the analysed systems.

Characterisation of three Amerindian populations from Hidalgo State (Mexico) by 15 STR-PCR polymorphisms.

The purpose of this study is to report allele frequency data of three ethnic Amerindian population samples: the Otomi (Hna-hnu) from eastern Sierra Madre and Ixmiquilpan valley and the Huasteco from La Huasteca. These groups were characterised by 15 STR-PCR polymorphisms (HumTH01, HumvWA, D18S51, HumTPOX, D19S433, D16S539, D13S317, D8S1179, D7S820, D5S818, HumFGA, CSF1PO, D2S1338, D3S1358 and D21S11). No significant deviations in observed allelic frequencies from Hardy-Weinberg equilibrium were found for all the studied systems. From the forensic point of view, the heterozygosity value, power of discrimination and the a priori chance of exclusion were calculated.