Parámetros forenses de diez microsatélites del cromosoma X en una muestra de la población del Estado Zulia, Venezuela / Forensic parameters of ten X chromosome microsatellites polymorphisms in a sample of the Zulia State population, Venezuela

Justificación:Las repeticiones cortas en tándem (STRs) están distribuidos por toda la extensión del genoma humano, los ubicados en los cromosomas autosómicos y en el cromosoma Y han sido ampliamente utilizados en los laboratorios de genética forense debido a las características y patrones hereditarios que estos poseen. ObjetivoA fin de caracterizar y determinar parámetros de interés forense en secuencias de tipo STR del cromosoma X (DXS8378, DXS9902, DXS7132, DXS9898, DXS6809, DXS6789, DXS7133, GATA172D05, GATA31E08 y DXS7423) en la población del Estado Zulia.Metodología:Se eligieron 108 individuos (130 cromosomas X),cuyos ADN se amplificaron mediante la reacción en cadena de la polimerasa, los fragmentos se separaron por electroforesis capilar y los alelos reportadoscon respecto a la escalera alélica. Resultados: El contenido de información polimórfica demostró ser mayor de 0,5 en todos los microsatélites y el poder de discriminación acumulado fue de 0,99999997 en mujeres y 0,99999816 en hombres.Conclusiones:Los datos demuestran que los microsatélites del cromosoma X analizados son lo suficientemente informativos como para ser utilizados en casos de vínculos biológicos complejos y la identificación humana...(AU)

Displasia ectodérmica hipohidrótica tipo 1 ligada al cromosoma X, síndrome de Christ-Siemens-Touraine: caso clínico y revisión de la literatura / Type 1 hypohidrotic ectodermal dysplasia X-linked, the Christ-Siemens-Touraine syndrome: a clinical case and review of the literature

La displasia ectodérmica hipohidrótica tipo 1 ligada al X (DEH1-X) ­síndrome de Christ-Siemens-Touraine­ es una genodermatosis que forma parte de las displasias ectodérmicas, caracterizadas por alteraciones en el desarrollo de una o más estructuras derivadas de ectodermo. Clínicamente presenta hipotricosis, hipohidrosis e hipodontia de severidad variable. Propósito: Describir las características clínicas de la DEH1-X, su manejo odontológico y diferenciarla de otras entidades patológicas. Caso clínico: Paciente masculino de 18 años de edad, con antecedente familiar de displasia ectodérmica hipohidrótica diagnosticada también en un hermano menor. Acude a consulta por prótesis anterior fracturada y mal ajustada. Se trató mediante frenilectomía anterior y rehabilitación bucal protésica. Discusión: En el diagnóstico y tratamiento de las alteraciones congénitas de desarrollo es de particular importancia la identificación temprana y el trabajo en equipo multidisciplinario. El plan de tratamiento y manejo clínico de tejidos orales blandos y duros debe ser adaptado a las necesidades particulares del padecimiento, lo que permitirá establecer un mejor pronóstico. Conclusiones: La DEH1-X es una alteración congénita del desarrollo que afecta estructuras orales, por lo que debe ser identificada por el estomatólogo para atender correctamente las alteraciones dentales y evitar complicaciones posteriores (AU)

Type 1 hypohidrotic ectodermal dysplasia X-linked (DEH1-X) -Christ-Siemens-Touraine syndrome- is a genodermatosis. Ectodermal dysplasias are characterized by development alterations on one or more ectodermal derived structures. IN DEH1-X, patients present hypotrichosis, hypohidrosis and hypodontia of variable severity. Aims: To describe anatomic and clinical characteristics of the DEH1-X, dental treatment, and to differentiate from other clinical conditions. Case report: Male teenager, 18-year-old, was referred for replacement of anterior dental prosthesis. Family history for hypohidrotic ectodermal dysplasia was positive, younger brother with the same condition. Treatment consisted of anterior labial frenectomy and dental prosthetic rehabilitation with acceptable clinical and esthetic's results. Discussion: When diagnosing and treating patients with developmental genetic conditions is particularly important the early detection and the participation of interdisciplinary team work. The clinical treatment of hard and soft tissues of the oral cavity has to be planned and personalized according to the particular needing of each case, in order to achieve better results and long term prognosis. Conclusions: DEH1-X is a congenital developmental disorder, which affects oral structures, should be identified and treated appropriately by the dentist to prevent further dental complications (AU)

Adrenomieloneuropatía, fenotipo de la adrenoleucodistrofia ligada al cromosoma X. Reporte de un caso / Adrenomyeoloneuropathy, X-linked adrenoleukodystrophy phenotype. A Case Report

Introducción: La adrenomieloneuropatía es una enfermedad peroxisomal, con patrón de herencia ligada al sexo. Es una variedad fenotípica de la adrenoleucodistrofia ligada al cromosoma X, esta última es también causa de insuficiencia adrenal. La adrenomieloneuropatía no pura cursa con insuficiencia adrenal. El diagnóstico de la enfermedad se hace por dosificación de ácidos grasos de cadena muy larga en suero. Para el diagnóstico de los fenotipos se emplean datos clínicos, anamnesis, datos de laboratorio y de imagen. Objetivo:Presentar un caso de adrenoleucodistrofia ligada al cromosoma X, fenotipo adrenomieloneuropatía, evaluado por reibergrama. Presentación del caso: Se presenta un caso de adrenomieloneuropatía e insuficiencia adrenal en un paciente masculino de 4 años de evolución, el cual ha sido hospitalizado en el Hospital Clínico-Quirúrgico Dr. Miguel Enríquez de La Habana, Cuba, en 2016 por un proceso respiratorio. Se diagnostica adrenoleucodistrofia ligada al cromosoma X, para identificar las variantes fenotípicas se tuvieron en cuenta los exámenes de laboratorio, técnicas imagenológicas, método clínico y una adecuada anamnesis. Conclusiones: El reibergrama puede contribuir al diagnóstico diferencial entre los fenotipos de la ADL-X y a la comprensión de la respuesta neuroinmunológica en esta enfermedad tal y como se demuestra en este caso(AU)

Introduction: Adrenomyeoloneuropathy is a peroxisomal disease with a sex-linked pattern of inheritance. It is a phenotypic variety of X-linked adrenoleukodystrophy; this last one is also a cause of adrenal insufficiency. Non-pure adrenomyeoloneuropathy occurs with adrenal insufficiency. The diagnosis of the disease is made by dosing very long chain fatty acids in serum. Clinical data, anamnesis, laboratory exams and imaging data are used for the diagnosis of phenotypes. Objective: To present a case of X-linked adrenoleukodystrophy, adrenomyeoloneuropathy phenotype, evaluated by Reibergram. Case presentation: We present a case of adrenomyeoloneuropathy and adrenal insufficiency in a male patient of 4 years of evolution who was admitted to Dr. Miguel Enríquez Clinical and Surgical Hospital, Havana, Cuba, 2016 because he was suffering from a respiratory process. The diagnosis of X-linked adrenoleukodystrophy was made. Laboratory exams, imaging techniques, the clinical method, and an adequate anamnesis were taken into account to for the identification of phenotypic variants. Conclusions: Reibergram can contribute to the differential diagnosis between ADL-X phenotypes and the understanding of the neuroimmunological response in this disease, as it is demonstrated in this case(AU)

Synaptic configuration of quadrivalents and their association with the XY bivalent in spermatocytes of Robertsonian heterozygotes of Mus domesticus

BACKGROUND: The nuclear architecture of meiotic prophase spermatocytes is based on higher-order patterns of spatial associations among chromosomal domains and consequently is prone to modification by chromosomal rearrangements. We have shown that nuclear architecture is modified in spermatocytes of Robertsonian (Rb) homozygotes of Mus domesticus. In this study we analyse the synaptic configuration of the quadrivalents formed in the meiotic pro- phase of spermatocytes of mice double heterozygotes for the dependent Rb chromosomes: Rbs 11.16 and 16.17. RESULTS: Electron microscope spreads of 60 pachytene spermatocytes from four animals of Mus domesticus 2n = 38 were studied and their respective quadrivalents analysed in detail. Normal synaptonemal complex was found between arms 16 of the Rb metacentric chromosomes, telocentrics 11 and 17 and homologous arms of the Rb metacentric chromosomes. About 43% of the quadrivalents formed a synaptonemal complex between the heterologous short arms of chromosomes 11 and 17. This synaptonemal complex is bound to the nuclear envelope through a fourth synapsed telomere, thus dragging the entire quadrivalent to the nuclear envelope. About 57% of quadrivalents showed unsynapsed single axes in the short arms of the telocentric chromosomes. About 90% of these unsynapsed quadrivalents also showed a telomere-to-telomere association between one of the single axes of the telocentric chromosome 11 or 17 and the X chromosome single axis, which was otherwise normally paired with the Y chromosome. Nucleolar material was associated with two bivalents and with the quadrivalent. CONCLUSIONS: The spermatocytes of heterozygotes for dependent Rb chromosomes formed a quadrivalent where four chromosomes are synapsed together and bound to the nuclear envelope through four telomeres. The nuclear configuration is determined by the fourth shortest telomere, which drags the centromere regions and heterochromatin of all the chromosomes towards the nuclear envelope, favouring the reiterated encounter and eventual rearrangement between the heterologous chromosomes. The unsynapsed regions of quadrivalents are frequently bound to the single axis of the X chromosome, possibly perturbing chromatin condensation and gene expression.

Síndrome oro-facial-digital / Oro-facial-digita syndrome

l síndrome orofaciodigital , es un grupo heterogéneo de trastornos del desarrollo de los cuales se han documentado al menos 13 variantes clínicas(1-3).Se transmite como un rasgo dominante ligado al cromosoma X. Se han reportado pocos casos en varones, ya que en general este trastorno genera letalidad en embriones masculinos en el primer o segundo semestre del embarazo (2).Conforma un cuadro clínicamente bien definido que debería ser reconocido en el recién nacido (4) y se asocia con manifestaciones clínicas a niveloral, facial y digital.El primer caso fue descrito por Mohr en 1941, seguido por un reporte de Papillon-League y Psaume en 1954; posteriormente, estos fueron denominados SOFD tipo 2 y 1, respectivamente (2,4).El SOFD tipo 1 a diferencia de los otros subtipos, es transmitido como un rasgo dominante ligado al cromosoma X. Es el único subtipo, del cual se ha identificado la mutación en el gen CXORF5, localizada en el brazo corto del cromosoma X (Xp22.2). El producto génico del SOFD1 es una proteína del centrosoma localizada en el cuerpo basal del cilio primario. (1-3,6). Se ha reportado una gran variabilidad clínica interfamiliar e intrafamiliar, así como 18 diferentes mutaciones en el SOFD 1 (6). La incidencia estimada es de 1: 50.000 a 250.000 nacidos vivos, afectando todas las razas por igual(2,5,6).Como su nombre lo indica, las principales manifestaciones se encuentran a nivel oral, facial y digital; sin embargo, otros órganos pueden estar afectados, lo que definiría el tipo específico de SOFD. Existen muy pocos casos reportados de los otros tipos, dada la amplia variabilidad en su expresión fenotípica; y también resulta muy dificultoso tipificar a los pacientes debido al solapamiento de las características clínicas (1-4). Entre las malformaciones orales se observan: labio superior muy corto, que suele acompañarse de una hendidura medial (45%) y frenillo grueso. El paladar se afecta con fisura medial amplia (80%) (Figs. 1 y 2); usualmente el paladar blando no existe, y en el óseo se presentan tres mamelones: uno central y dos laterales. El maxilar inferior dispone bandas fibrosas (frenillos) que adhieren los labios a las arcadas dentarias, las cuales están hendidas. Estas bandas se adhieren a la lengua fijándolas (anquiloglosia) y dividiéndola en varios mamelones (30-45%) (Figs. 1 y 2); muchas veces se encuentra tejido hamartomatoso (70%). El maxilar inferior también es hipoplásico y existe mala oclusión dentaria. (Fig. 2) Servin, Roxana y Col. Rev.Fac. Med. UNNE XXXVII: 1, 42-46, 2017Las malformaciones faciales incluyen: hipertelorismo, raíz nasal ancha con punta fina e hipoplasia de los cartílagos de las alas nasales; narinas pequeñas y antevertidas con diferencia de tamaño. También suelen apreciarse un aplanamiento mediofacial. La piel presenta millium en mejillas, frente y pabellón auricular (Figs. 1 y 2). Hay xerodermia y puede haber alopecía en cuero cabelludo. El pelo es seco y quebradizo. (Fig. 1)En miembros, las alteraciones más frecuentes se observan en manos (45%) tales como clinodactilia, braquidactilia y sindactilia. (Figs. 1 y 2)En los pies puede haber polisindactilia (casi siempre unilateral, preaxial). Los demás dedos son cortos e hipoplásicos. Fig. 1.Paciente de 10 meses, con los rasgos característicos. Arriba izq. labio superior fino, fisura palatina, mamelones linguales y milium en mejillas. Arriba der.clino y braquidactilia. Abajo: alopecia, cabello seco y quebradizo. Servin, Roxana y Col. Rev. Fac. Med. UNNE XXXVII: 1, 42-46, 2017A nivel de sistema nervioso central las malformaciones son variables (40%) puede existir porencefalia o hidrocefalia (que comúnmente se acompaña a agenesia total o parcial del cuerpo calloso), y su asociación con un retardo mental (40%). En aparato urinario se observan riñones poliquísticos en un 50% de los casos. El esqueleto también se ve afectado, evidenciándose huesos cortos y gruesos en manos y pies, muchas veces con osteoporosis (2-5,6).Los subtipos de este síndrome presentan características distintivas. La polidactilia se presenta en todos los subtipos, por lo que obviando esta característica, se menciona la Fig. 2.Madre de la paciente. Arriba izq. maloclusión dentaria, mamelones linguales y milium en mejillas. Arriba der. fisura palatina. Abajo: clino, braquidactilia, y en mano derecha sindactilia cutánea (membrana interdigital). Servin, Roxana y Col. Rev. Fac. Med. UNNE XXXVII: 1, 42-46, 2017clínica particular de los otros subtipos. El SOFD 1 es de carácter autosómico dominante ligado al X, predominando el millium y la poliquistosis renal. En el SOFD 2 (o Síndrome de Mohr-Majewski) se puede manifestar punta nasal bífida. La característica delSOFD 3 es el guiño ocular en sube y baja (alternado), los espasmos mioclónicos y el retraso mental. La nariz es bulbosa y las orejas son de implantación baja. En el SOFD 4 hay compromiso tibial, pectus excavatum y baja estatura. El SOFD 5 presenta fisura labial medial aislada. En el SOFD 6 (o Síndrome de Váradi-Papp) se distingue la polidactilia principalmente media y con metacarpos en forma de "Y"; también malformación cerebelar (ausencia de vermis). Se puede observar además displasia y agenesia renal (2).El SOFD 7 (o Síndrome de Whelan) fue reportado una sola vez, como un subtipo que compartía características del tipo 1 y 2. Durante el seguimiento, la paciente desarrolló clínica inherente al SOFD 1, por lo que se concluyó que inicialmente pertenecía al tipo 1, y se removió el SOFD 7 de la clasificación (8). El SOFD 8 es de herencia recesiva ligada al X. Clínicamente presenta, defectos tibiales, radiales y anormalidades epiglóticas. Por último, el SOFD 9 se caracteriza por anormalidades retinianas y fisura labial no medial (2).Es posible para el médico poder sospechar el diagnóstico de SOFD 1 mediante la fetoscopía o ultrasonografía, siendo la detección de polidactilia y defectos faciales, parámetros fundamentales; no obstante el diagnóstico es eminentemente clínico y debe hacerse en el recién nacido. Los diagnósticos diferenciales deben plantearse principalmente con subtipos de SOFD (2,4). Es de importancia la participación de un equipo multidisciplinario integrado por genetistas, pediatras, dermatólogos, cirujanos máxilo-faciales, psicólogos, odontopediatras para brindar asesoramiento y asistencia a estos pacientes. Aunque el pronóstico depende de las manifestaciones clínicas específicas y la gravedad de las mismas, es importante la identificación del tipo que presenta porque nos orientará en los estudios diagnósticos de otras posibles manifestaciones clínicas asociadas a ese tipo en particular (

Chromosomal divergence and evolutionary inferences in Rhodniini based on the chromosomal location of ribosomal genes

In this study, we used fluorescence in situ hybridisation to determine the chromosomal location of 45S rDNA clusters in 10 species of the tribe Rhodniini (Hemiptera: Reduviidae: Triatominae). The results showed striking inter and intraspecific variability, with the location of the rDNA clusters restricted to sex chromosomes with two patterns: either on one (X chromosome) or both sex chromosomes (X and Y chromosomes). This variation occurs within a genus that has an unchanging diploid chromosome number (2n = 22, including 20 autosomes and 2 sex chromosomes) and a similar chromosome size and genomic DNA content, reflecting a genome dynamic not revealed by these chromosome traits. The rDNA variation in closely related species and the intraspecific polymorphism in Rhodnius ecuadoriensis suggested that the chromosomal position of rDNA clusters might be a useful marker to identify recently diverged species or populations. We discuss the ancestral position of ribosomal genes in the tribe Rhodniini and the possible mechanisms involved in the variation of the rDNA clusters, including the loss of rDNA loci on the Y chromosome, transposition and ectopic pairing. The last two processes involve chromosomal exchanges between both sex chromosomes, in contrast to the widely accepted idea that the achiasmatic sex chromosomes of Heteroptera do not interchange sequences.

Rapid detection of chromosome X, Y, 13, 18, and 21 aneuploidies by primed in situ labeling/synthesis technique.

AIMS AND OBJECTIVE: Primed in situ labeling/synthesis (PRINS) technique is an alternative to fluorescent in situ hybridization for chromosome analysis. This study was designed to evaluate the application of PRINS for rapid diagnosis of common chromosomal aneuploidy. MATERIALS AND METHODS: We have carried out PRINS using centromere specific oligonucleotide primers for chromosome X, Y, 13, 18 and 21 on lymphocyte metaphase and interphase cells spread. Specific primer was annealed in situ, followed by elongation of primer by Taq DNA polymerase in presence of labeled nucleotides. Finally, reaction was stopped and visualized directly under fluorescent microscope. RESULTS: Discrete centromere specific signals were observed with each primer. CONCLUSION: PRINS seems to be a rapid and reliable method to detect common chromosome aneuploidy in peripheral blood lymphocyte metaphase and interphase cells.

Isochromosome X mosaicism in a child with Kabuki syndrome phenotype: A rare cytogenetic association.

Isochromosome is a structurally unbalanced chromosome consisting of two short arms or two long arms, which are derived by abnormal centromere division or sister-chromatid exchange. Most autosomal isochromosomes are unusual, while those involving sex chromosomes are common. Kabuki syndrome (KS, OMIM 147920) is a multiple malformation/mental retardation syndrome of unknown etiology. A conventional cytogenetic study on lymphocytes from a 4-year-old girl with physical features suggestive of KS was found to have mosaicism for isochromosome for the long arm of the X. Although most manifestations present in this patient have been described before, this report is a rare association of clinical and cytogenetic findings in this syndrome. A genome-wide analysis and a larger number of patient groups studied could improve our understanding of the genetic basis of KS.

Karyotype and male pre-reductional meiosis of the sharpshooter Tapajosa rubromarginata (Hemiptera: Cicadellidae)

Cicadellidae in one of the best represented families in the Neotropical Region, and the tribe Proconiini comprises most of the xylem-feeding insects, including the majority of the known vectors of xylem-born phytopathogenic organisms. The cytogenetics of the Proconiini remains largely unexplored. We studied males of Tapajosa rubromarginata (Signoret) collected at El Manantial (Tucumán, Argentina) on native spontaneous vegetation where Sorghum halepense predominates. Conventional cytogenetic techniques were used in order to describe the karyotype and male meiosis of this sharpshooter. T. rubromarginata has a male karyological formula of 2n=21 and a sex chromosome system XO:XX (♂:♀). The chromosomes do not have a primary constriction, being holokinetic and the meiosis is pre-reductional, showing similar behavior both for autosomes and sex chromosomes during anaphase I. For this stage, chromosomes are parallel to the acromatic spindle with kinetic activities in the telomeres. They segregate reductionally in the anaphase I, and towards the equator during the second division of the meiosis. This is the first contribution to cytogenetic aspects on proconines sharpshooters, particularly on this economic relevant Auchenorrhyncha species. Rev. Biol. Trop. 59 (1): 309-314. Epub 2011 March 01.

Los Cicadellidae son una de las familias mejor representadas en la región neotropical. La tribu Proconiini incluye a muchos de los insectos que se alimentan de xilema y la mayoría de los vectores de organismos fitopatógenos asociados con dicho tejido de conducción. La citogenética de los Proconiini es prácticamente inexplorada. Por lo tanto, se utilizaron técnicas citogenéticas convencionales para describir el cariotipo y la meiosis en los machos de Tapajosa rubromarginata Signoret. Este cicadélido presenta el complemento cromosómico diploide de 2n=20A+X0 en los machos. Los cromosomas no presentan constricción primaria, son holocinéticos, y la meiosis es pre-reduccional, muestra un comportamiento similar tanto en los cromosomas sexuales como en los autosómicos durante la anafase I. En ese estado, los cromosomas se orientan de manera paralela a las fibras del huso acromático con actividad cinética en los telómeros y segregan de manera reduccional en la fase I y ecuacional en la fase II de la meiosis.

Falência ovariana prematura: aspectos genéticos / Premature ovarian failure: genetic aspects

A falência ovariana prematura exige, para avaliação conveniente dos diversos fenômenos etiológicos envolvidos, adequada análise de seus fatores causais. Entre as possíveis causas genéticas, encontram-se anomalias gênicas ou cromossômicas, seja nos cromossomos X ou nos autossomos. O presente estudo apresenta, de modo sucinto, revisão dos fatores genéticos que são responsáveis por tais fenômenos etiológicos.

Premature ovarian failure demands a proper analysis of countless factors for an accurate assessment of the several etiological phenomena processes involved. Among the possible genetic causes, it has been detected genic of chromossomal anomalies, ocurring either on the sex chromosomes or on the autosomes. This study presents a review of the genetic and chromosomal factors which account for etiological phenomena.

Falência ovariana precoce em portadores da pré-mutação do gene FMR1: revisão da literatura / Premature ovarian failure in FMR1 premutation carriers: a literature review

A mutação do gene FMR1 é um fator genético importante para a determinação multifatorial da idade da menopausa. Portadoras da pré-mutação podem ter a vida reprodutiva encurtada e devem ser alertadas sobre o risco de transmissão da Síndrome do X Frágil para seus descendentes. O objetivo deste trabalho foi mostrar dados atualizados sobre as implicações genotípica e fenotípica da pré-mutação do gene FMR1 na reprodução humana.

The FMR1 mutation is an important genetic factor in the multifactor determination of menopause age. Premutation carriers can have reproductive life shortened and should be alerted about the risk of transmitting the Fragile X Syndrome to their descendents. The purpose of this paper was to show updated data about the genotypic and phenotypic implications of FMR1 premutation on human reproduction.

Expression and identification of folate-sensitive fragile sites in British Suffolk sheep (Ovis aries).

An investigation to understand the dynamics and biological significance of fragile site expression, and identification of 5-fluorodeoxyuridine (FUdR) induced chromosomal gaps/breaks, were carried out in an experimental flock of 45 Suffolk sheep. The statistical comparison revealed, highly significant variation in the frequency of chromosomal fragile site expression between control and FUdR cultures. Mean (+/- S.D.) values for cells with gaps and breaks, or aberrant cell count (AC), and the number of aberrations (NoA) per animal were 2.02 +/- 0.34, 2.42 +/- 0.48, 13.26 +/- 0.85 and 21.87 +/- 1.88 (P lessthan 0.01) in control and FUdR cultures, respectively. The comparison of age revealed nonsignificant variation between control and FUdR cultures. The G-band analysis of fragile site data revealed gaps in 29 autosomal and two X-chromosomal bands in the control cultures, whereas FUdR treated cultures scored 78 unstable bands in autosomes of which 56 were significantly fragile. X-chromosomes expressed breaks and gaps in six G-negative bands and five of them (Xq13, Xq15, Xq17, Xq24 and Xq26) were significantly fragile. The distribution comparison of autosomal fragile sites between sex groups did not reveal any significant variation. Female X-chromosomes were significantly more fragile than the male X-chromosomes. The distribution comparison for age groups (lambs versus adults) revealed significantly higher number of fragile bands in adults. Comparison of published data on reciprocal translocations in sheep with the fragile-site data obtained in this study indicated that the break sites of both phenomena were correlated. Similarities were also found between fragile sites and breakpoints of evolutionary significance in family Bovidae.

Análisis de STRs de cromosoma X: su utilidad en casos de filiación / Analysis of X-Chromosome markers: utility in paternity identification

Analysis of X-chromosome markers is being increasingly used in special paternity cases. Here, we present a complex case composed of mother, child and three sibs of the decaesed alleged father. Exlcusion of the alleged biological relationships between child and the alleged group could be confirmed by typing a set of 10 X-chromosome STRs (short tandem repeat) in addition to the 17 autosomal STRs routinely analyzed, proving that analyses of these X-chromosome STRs is a useful supplementary tool in special situations of disputed paternity.

Drosophila simulans Lethal hybrid rescue mutation (Lhr) rescues inviable hybrids by restoring X chromosomal dosage compensation and causes fluctuating asymmetry of development.

The Drosophila simulans Lhr rescues lethal hybrids from the cross of D. melanogaster and D. simulans. We describe here, the phenotypes of Lhr dependent rescue hybrids and demonstrate the effects of Lhr on functional morphology of the salivary chromosomes in the hybrids. Our results reveal that the phenotypes of the 'Lhr dependent rescued' hybrids were largely dependent on the genetic background and the dominance in species and hybrids, and not on Lhr. Cytological examination reveal that while the salivary chromosome of 'larval lethal' male carrying melanogaster X chromosome was unusually thin and contracted, in 'rescued' hybrid males (C(mel)X(mel)Y(sim); A(mel)A(sim)) the X chromosome showed typical pale staining, enlarged diameter and incorporated higher rate of (3)H-uridine in presence of one dose Lhr in the genome. In hybrid males carrying simulans X chromosome (C(mel)X(sim)Y(mel); A(mel)A(sim)), enlarged width of the polytene X chromosome was noted in most of the nuclei, in Lhr background, and transcribed at higher rate than that of the single X chromosome of male. In hybrid females (both viable, e.g., C(mel)X(mel)X(sim); A(mel)A(sim) and rescued, e.g., C(mel)X(mel)X(mel); A(mel)A(sim)), the functional morphology of the X chromosomes were comparable to that of diploid autosomes in presence of one dose of Lhr. In hybrid metafemales (C(mel)X(mel)X(mel)X(sim); A(mel)A(sim)), two dose of melanogaster X chromosomes and one dose of simulans X chromosome were transcribed almost at 'female' rate in hybrid genetic background in presence of one dose of Lhr. In rescued hybrid males, the melanogaster-derived X chromosome appeared to complete its replication faster than autosomes. These results together have been interpreted to have suggested that Lhr suppresses the lethality of hybrids by regulating functional activities of the X chromosome(s) for dosage compensation.

New evidence for nucleolar dominance in hybrids of Drosophila arizonae and Drosophila mulleri

Drosophila mulleri (MU) and D. arizonae (AR) are cryptic species of the mulleri complex, mulleri subgroup, repleta group. Earlier cytogenetic studies revealed that these species have different regulatory mechanisms of nucleolar organizing activity. In these species, nucleolar organizing regions are found in both the X chromosome and the microchromosome. In the salivary glands of hybrids between MU females and AR males, there is an interspecific dominance of the regulatory system of the D. arizonae nucleolar organizer involving, in males, amplification and activation of the nucleolar organizer from the microchromosome. The authors who reported these findings obtained hybrids only in that cross-direction. More recently, hybrids in the opposite direction, i.e., between MU males and AR females, have been obtained. The purpose of the present study was to evaluate, in these hybrids, the association of the nucleoli with the chromosomes inherited from parental species in order to cytogenetically confirm the dominance patterns previously described. Our results support the proposed dominance of the AR nucleolar organizer activity over that of MU, regardless of cross-direction.

Metilación del ADN: un fenómeno epigenético de importancia médica / DNA methylation: an epigenetic process of medical importance

Methylation of CpG dinucleotides is an epigenetic mechanism involved in the regulation of gene expression in mammals. The patterns of CpG methylation are specie and tissue specific. The biological machinery of this system comprises a variety of regulatory proteins including DNA methyltransferases, putative demethylases, methyl-CpG binding proteins, histones modifying enzymes and chromatin remodeling complexes. DNA methylation maintains gene silencing and participates in normal development, genomic imprinting and X chromosome inactivation. In contrast, alterations in DNA methylation participate in the induction of some human diseases, especially those involving developmental defects and tumorigenesis. This review summarizes the molecular aspects of DNA methylation and its implications in cancer and other human diseases in which this epigenetic mechanism has been involved. Our understanding of the epigenetic changes that occur in human diseases will be very important for future management. Changes in the patterns of methylation can be used as markers in cancer and their potentially reversible state creates a target for therapeutic strategies involving specific gene re-activation or re-silencing.

La metilación del ADN en dinucleótidos CpG es uno de los mecanismos epigenéticos implicados en la regulación de la expresión génica en mamíferos. Los patrones de metilación son específicos para cada especie y tipo de tejido. La maquinaria implicada comprende diferentes proteínas reguladoras incluyendo a las ADN metiltransferasas, desmetilasas putativas, proteínas de unión a CpG metilados, enzimas modificadoras de histonas y complejos remodeladores de la cromatina. La metilación del ADN es de vital importancia para mantener el silenciamiento génico en el desarrollo normal, la impronta genómica y la inactivación del cromosoma X. En contraste, alteraciones en ella están implicadas en algunas enfermedades humanas, especialmente aquéllas relacionadas con defectos en el desarrollo y el proceso neoplásico. Esta revisión resume los aspectos moleculares de la metilación del ADN y su participación en el desarrollo normal, el cáncer y en algunas patologías humanas en las que los mecanismos epigenéticos han sido implicados. El conocimiento de las modificaciones epigenéticas que ocurren en las enfermedades humanas será importante para su manejo futuro. Los cambios en los patrones de metilación podrán ser empleados como marcadores en cáncer y el estado potencialmente reversible de este proceso constituye un blanco ideal para crear estrategias terapéuticas que impliquen la reactivación o el re-silenciamiento de genes específicos.

Molecular detection of XO - Turner syndrome

Turner syndrome is caused by haploinsufficiency of the short arm of X-chromosome, and is usually diagnosed by karyotyping. This procedure is time-consuming, expensive and unfeasible for population screening. We propose molecular detection of 45XO Turner patients based on the ability of HpaII, a methylation sensitive endonuclease, to induce the cleavage of non-methylated DNA in the active X-allele. Genomic DNA was obtained from 22 patients with Turner syndrome confirmed by karyotype (45XO, N = 18; 45XO/46XX, N = 4). After digestion, DNA was amplified with primers directed to exon 1 of the androgen receptor (AR) gene and to the GAPDH control gene. Normal control females or mosaic patients, with a second methylated X-chromosome, escaped from HpaII digestion and produced a band corresponding to AR gene amplification. 45XO patients have just one active non-methylated X-chromosome, completely digested by HpaII, thus preventing the amplification of the AR gene. Three of the 45XO cases gave amplified bands, suggesting low-frequency mosaicisms that are not detected by karyotyping. Compared to classical karyotype studies for the detection of 45XO Turner patients, this new molecular method is simpler, faster and less expensive.

Molecular insights into the causes of male infertility.

Infertility is a reproductive health problem that affects many couples in the human population. About 13-18% of couple suffers from it and approximately one-half of all cases can be traced to either partner. Regardless of whether it is primary or secondary infertility, affected couples suffer from enormous emotional and psychological trauma and it can constitute a major life crisis in the social context. Many cases of idiopathic infertility have a genetic or molecular basis. The knowledge of the molecular genetics of male infertility is developing rapidly, new "spermatogenic genes" are being discovered and molecular diagnostic approaches (DNA chips) established. This will immensely help diagnostic and therapeutic approaches to alleviate human infertility. The present review provides an overview of the causes of human infertility, particularly the molecular basis of male infertility and its implications for clinical practice.