Gene dosage of DAX-1, determining in sexual differentiation : duplication of DAX-1 in two sisters with gonadal dysgenesis

Q3Q2Artículo original2971-2978Two sisters phenotypically normal females, presenting with tumor abdominal mass with histopathological findings of teratoma and gonadoblastoma associated to 46,XY male-to-female sex reversal syndrome, secondary to a duplication in DAX-1, possibly inherited of maternal gonadal mosaicism. Copy number variation and functional effects of the duplication were done by MLPA multiplex ligation-dependent probe amplification and real time PCR. DAX-1, also known as dosage sensitive sex reversal gene (DSS), is considered the most likely candidate gene involved in XY gonadal dysgenesis when overexpressed. The excess of DAX-1 gene disturbs testicular development by down regulation of SF-1, WT1, and SOX9. This is the first report of 46,XY sex reversal in two siblings who have a maternally inherited duplication of DAX-1 associated with reduced levels of expression of downstream genes as SOX9-SF1

Condiciones óptimas de cultivo de linfocitos y análisis parcial del cariotipo de la tortuga cabezona, Caretta caretta (Testudines: Cheloniidae) en Santa Marta, Caribe Colombiano

En los últimos años se ha registrado una disminución importante en el número de individuos de la tortuga marina Caretta caretta anidantes en el Caribe colombiano, situación que pone en evidencia la posibilidad de su extinción a mediano plazo. Por esto, es necesario implementar planes para su manejo y conservación. En este estudio se determinaron los requerimientos del cultivo de linfocitos de Caretta caretta para la obtención de cariotipos que permitan la identificación citogenética, el estudio inmunológico y toxicológico de individuos sin necesidad de sacrificarlos. Se muestrearon 47 individuos de C. caretta de Santa Marta, Colombia obteniendo sangre periférica con la que se realizaron ensayos de las diferentes variables hasta obtener las condiciones óptimas para el cultivo convencional de linfocitos. El cariotipo obtenido presentó 56 cromosomas: 32 macrocromosomas y 24 microcromosomas. El ideograma mostró que C. caretta tiene cuatro grupos de cromosomas: el grupo A compuesto por doce (12) pares de cromosomas de mayor tamaño. El Grupo B compuesto por cuatro (4) pares de cromosomas medianos y pequeños y el Grupo C conformado por 12 pares de microcromosomas. No se observaron cromosomas sexuales. Estos resultados están en desacuerdo con el cariotipo descrito por Kamesaki (1989), debido posiblemente a que las muestras analizadas en ese estudio fueron colectadas en el Océano Pacifico (Japón). El presente estudio es el primero realizado con tortugas del Océano Atlántico que cuenta con la descripción completa de la morfología cromosómica. Es posible, que una de las estrategias adaptativas de esta especie sea el intercambio genético con otras especies de la familia, que produce individuos híbridos viables. En este aspecto se ha descrito la hibridación de tortugas Caretta caretta con Eretmochelys imbricata, Chelonia mydas y Lepidochelys kempii, esto sugiere la posibilidad que los individuos caracterizados en este estudio sean híbridos viables de C. caretta, por lo tanto, se hace necesario realizar estudios a nivel molecular

Genome-wide association study of germline variants and breast cancer-specific mortality

AbstractBackground: We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry.Methods: Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP).Results: We did not find any variant associated with breast cancer-specific mortality at P −8. For ER-positive disease, the most significantly associated variant was chr7:rs4717568 (BFDP = 7%, P = 1.28 × 10−7, hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.84–0.92); the closest gene is AUTS2. For ER-negative disease, the most significant variant was chr7:rs67918676 (BFDP = 11%, P = 1.38 × 10−7, HR = 1.27, 95% CI = 1.16–1.39); located within a long intergenic non-coding RNA gene (AC004009.3), close to the HOXA gene cluster.Conclusions: We uncovered germline variants on chromosome 7 at BFDP Abstract Background: We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry. Methods: Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP). Results: We did not find any variant associated with breast cancer-specific mortality at P < 5 × 10−8. For ER-positive disease, the most significantly associated variant was chr7:rs4717568 (BFDP = 7%, P = 1.28 × 10−7, hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.84–0.92); the closest gene is AUTS2. For ER-negative disease, the most significant variant was chr7:rs67918676 (BFDP = 11%, P = 1.38 × 10−7, HR = 1.27, 95% CI = 1.16–1.39); located within a long intergenic non-coding RNA gene (AC004009.3), close to the HOXA gene cluster. Conclusions: We uncovered germline variants on chromosome 7 at BFDP < 15% close to genes for which there is biological evidence related to breast cancer outcome. However, the paucity of variants associated with mortality at genome-wide significance underpins the challenge in providing genetic-based individualised prognostic information for breast cancer patients

Consideraciones sobre la historia de la prioridad taxonómica de oncidium ornithorhynchum

La historia de la prioridad taxonómica de la orquídea Oncidium ornithorhynchum está aún por aclarar si se consideran las diferentes descripciones y publicaciones de esta especie propuestas en los siglos XVIII y XIX por botánicos como José Celestino Mutis, John Lindley, Alexander von Humboldt, Aimé Bonpland y Carl S. Kunth, entre otros. Con el fin de resolver las inconsistencias en los reportes taxonómicos de esta especie en el transcurso del tiempo, y teniendo como base la reciente aclaración realizada por Jiménez y Hágsater sobre la identidad del ejemplar tipo conservado en París, hemos procedido a ordenar las fuentes primarias asociadas con su descripción y nomenclatura botánica.The history of the nomenclatural taxonomic priority of the orchid Oncidium ornithorhynchum is yet to be clarified, as successive descriptions and publications of this species were proposed in the eighteenth and nineteenth centuries by botanists such as José Celestino Mutis, John Lindley, Alexander von Humboldt, Aimé Bonpland and Carl S. Kunth, among others. In order to resolve the inconsistencies in taxonomic reports of this species in the course of time, and based on the recent clarification by Jiménez and Hágsater on the type specimen conserved in Paris, we proceeded to review the primary sources associated with its description and botanical nomenclature

Birth defects surveillance: experiences in Argentina and Colombia

Birth defects (BDs) are structural or functional anomalies, sporadic or hereditary, of prenatal origin. Public health surveillance is defined as the ongoing systematic collection, analysis, and interpretation of outcome-specific data for use in the planning, implementation, and evaluation of public health practice. BD surveillance systems may have different characteristics according to design, coverage, type of surveillance, case ascertainment, case definition, BD description, maximum age of diagnosis, pregnancy outcomes, coding systems, and the location of the coding process (central or local). The aim of this article is to describe and compare methodology, applications, and results of birth defect surveillance systems in two South-American countries: Colombia and Argentina. In both countries, the surveillance systems developed activities in relation to the Zika virus emergency. For most BDs, a statistically significant higher prevalence is observed in Argentina-RENAC than in Colombian registries. This may be due to methodological reasons or real differences in prevalence. The strengths, weaknesses, and the future perspectives of the Argentine and Colombian systems are presented. When developing a surveillance system, the objectives, the available resources, and previous experiences in similar contexts must be taken into account. In that sense, the experience of Argentina and Colombia can be useful for others when developing a birth defect surveillance system.Fil: Groisman, Boris. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Centro Nacional de Genética Médica; ArgentinaFil: Liascovich, Rosa. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Centro Nacional de Genética Médica; ArgentinaFil: Bidondo, Maria Paz. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Centro Nacional de Genética Médica; ArgentinaFil: Barbero, Pablo Miguel. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Centro Nacional de Genética Médica; ArgentinaFil: Duarte, Santiago Pablo. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Centro Nacional de Genética Médica; ArgentinaFil: Tellechea, Ana Laura. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Centro Nacional de Genética Médica; ArgentinaFil: Holguín, Jorge. Pontificia Universidad Javeriana; ColombiaFil: Rodríguez, Catherine. Secretaría Distrital de Salud; ColombiaFil: Hurtado Villa, Paula. Pontificia Universidad Javeriana; ColombiaFil: Caicedo, Natalia. Pontificia Universidad Javeriana; ColombiaFil: Botta, Gabriela. Pontificia Universidad Javeriana; ColombiaFil: Zarante Montoya, Ignacio Manuel. Pontificia Universidad Javeriana; Colombi

Trisomy 13 and 18—Prevalence and mortality—A multi‐registry population based analysis

The aim of the study is to determine the prevalence, outcomes, and survival (among live births [LB]), in pregnancies diagnosed with trisomy 13 (T13) and 18 (T18), by congenital anomaly register and region. Twenty‐four population‐ and hospital‐based birth defects surveillance registers from 18 countries, contributed data on T13 and T18 between 1974 and 2014 using a common data‐reporting protocol. The mean total birth prevalence (i.e., LB, stillbirths, and elective termination of pregnancy for fetal anomalies [ETOPFA]) in the registers with ETOPFA (n = 15) for T13 was 1.68 (95% CI 1.3–2.06), and for T18 was 4.08 (95% CI 3.01–5.15), per 10,000 births. The prevalence varied among the various registers. The mean prevalence among LB in all registers for T13 was 0.55 (95%CI 0.38–0.72), and for T18 was 1.07 (95% CI 0.77–1.38), per 10,000 births. The median mortality in the first week of life was 48% for T13 and 42% for T18, across all registers, half of which occurred on the first day of life. Across 16 registers with complete 1‐year follow‐up, mortality in first year of life was 87% for T13 and 88% for T18. This study provides an international perspective on prevalence and mortality of T13 and T18. Overall outcomes and survival among LB were poor with about half of live born infants not surviving first week of life; nevertheless about 10% survived the first year of life. Prevalence and outcomes varied by country and termination policies. The study highlights the variation in screening, data collection, and reporting practices for these conditions

Five polymorphisms and breast cancer risk: results from the Breast Cancer Association Consortium.

Previous studies have suggested that minor alleles for ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 may influence breast cancer risk, but the evidence is inconclusive due to their small sample size. These polymorphisms were genotyped in more than 30,000 breast cancer cases and 30,000 controls, primarily of European descent, from 30 studies in the Breast Cancer Association Consortium. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) as a measure of association. We found that the minor alleles for these polymorphisms were not related to invasive breast cancer risk overall in women of European descent: ECCR4 per-allele OR (95% CI) = 0.99 (0.97-1.02), minor allele frequency = 27.5%; TNF 1.00 (0.95-1.06), 5.0%; CASP10 1.02 (0.98-1.07), 6.5%; PGR 1.02 (0.99-1.06), 15.3%; and BID 0.98 (0.86-1.12), 1.7%. However, we observed significant between-study heterogeneity for associations with risk for single-nucleotide polymorphisms (SNP) in CASP10, PGR, and BID. Estimates were imprecise for women of Asian and African descent due to small numbers and lower minor allele frequencies (with the exception of BID SNP). The ORs for each copy of the minor allele were not significantly different by estrogen or progesterone receptor status, nor were any significant interactions found between the polymorphisms and age or family history of breast cancer. In conclusion, our data provide persuasive evidence against an overall association between invasive breast cancer risk and ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 genotypes among women of European descent

Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry

PurposeType 2 diabetes (T2D) has been reported to be associated with an elevated risk of breast cancer. It is unclear, however, whether this association is due to shared genetic factors.MethodsWe constructed a genetic risk score (GRS) using risk variants from 33 known independent T2D susceptibility loci and evaluated its relation to breast cancer risk using the data from two consortia, including 62,328 breast cancer patients and 83,817 controls of European ancestry. Unconditional logistic regression models were used to derive adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) to measure the association of breast cancer risk with T2D GRS or T2D-associated genetic risk variants. Meta-analyses were conducted to obtain summary ORs across all studies.ResultsThe T2D GRS was not found to be associated with breast cancer risk, overall, by menopausal status, or for estrogen receptor positive or negative breast cancer. Three T2D associated risk variants were individually associated with breast cancer risk after adjustment for multiple comparisons using the Bonferroni method (at p &lt; 0.001), rs9939609 (FTO) (OR 0.94, 95 % CI = 0.92-0.95, p = 4.13E-13), rs7903146 (TCF7L2) (OR 1.04, 95 % CI = 1.02-1.06, p = 1.26E-05), and rs8042680 (PRC1) (OR 0.97, 95 % CI = 0.95-0.99, p = 8.05E-04).ConclusionsWe have shown that several genetic risk variants were associated with the risk of both T2D and breast cancer. However, overall genetic susceptibility to T2D may not be related to breast cancer risk