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1.
Cytogenet Genome Res ; 158(3): 160-169, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31394537

RESUMO

The discovery of sex chromosome systems in non-model organisms has elicited growing recognition that sex chromosomes evolved via diverse paths that are not fully elucidated. Lineages with labile sex determination, such as turtles, hold critical cues, yet data are skewed toward hide-neck turtles (suborder Cryptodira) and scant for side-neck turtles (suborder Pleurodira). Here, we used classic and molecular cytogenetics to investigate Emydura subglobosa (ESU), an unstudied side-neck turtle with genotypic sex determination from the family Chelidae, where extensive morphological divergence exists among XX/XY systems. Our data represent the first cytogenetic description for ESU. Similarities were found between ESU and E. macquarii (EMA), such as identical chromosome number (2n = 50), a single and dimorphic nucleolus organizer region (NOR) localized in a microchromosome pair (ESU14) of both sexes (detected via FISH of 18S rDNA). Only the larger NOR is active (detected by silver staining). As in EMA, comparative genome hybridization revealed putative macro XX/XY chromosomes in ESU (the 4th largest pair). Our comparative analyses and revaluation of previous data strongly support the hypothesis that Emydura's XX/XY system evolved via fusion of an ancestral micro-Y (retained by Chelodina longicollis) onto a macro-autosome. This evolutionary trajectory differs from the purported independent evolution of XX/XY from separate ancestral autosomes in Chelodina and Emydura that was previously reported. Our data permit dating this Y-autosome fusion to at least the split of Emydura around 45 Mya and add critical information about the evolution of the remarkable diversity of sex-determining mechanisms in turtles, reptiles, and vertebrates.


Assuntos
Evolução Molecular , Cromossomos Sexuais/genética , Tartarugas/genética , Animais , Hibridização Genômica Comparativa , Hibridização in Situ Fluorescente , Cariótipo , Masculino , Repetições de Microssatélites/genética , RNA Ribossômico 18S/genética , Coloração pela Prata , Tartarugas/classificação
2.
Presse Med ; 48(7-8 Pt 1): 816-824, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31439443

RESUMO

Diagnosis of mature B cell malignancies is highly multidisciplinary. Biological tools provide diagnostic, prognostic and theranostic information. Biological hematology allows considering mature B cell diseases from two perspectives : cellular and molecular approaches. Cytomorphology and flow cytometry are tools from cell hematology. Conventional cytogenetics, FISH and molecular biology are tools from molecular hematology. NGS is a new technique that could dramatically change diagnostic and therapeutic management of B cell malignancies in the near future. Integration of clinical, pathological and biological data allows for personalized management of these diseases.


Assuntos
Técnicas de Laboratório Clínico/métodos , Leucemia de Células B/diagnóstico , Linfoma de Células B/diagnóstico , Integração de Sistemas , Hibridização Genômica Comparativa/métodos , Citodiagnóstico/métodos , Análise Citogenética/métodos , Análise Mutacional de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Imunofenotipagem/métodos , Hibridização in Situ Fluorescente/métodos , Leucemia de Células B/genética , Leucemia de Células B/patologia , Linfoma de Células B/genética , Linfoma de Células B/patologia , Técnicas de Diagnóstico Molecular/métodos , Imagem Multimodal/métodos , Imagem Multimodal/tendências
3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(8): 813-816, 2019 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-31400135

RESUMO

OBJECTIVE: To carry out prenatal diagnosis for a fetus with ultrasonographic abnormality. METHODS: Chromosomal karyotyping and array comparative genomic hybridization (array-CGH) analysis were applied for the diagnosis. Peripheral blood samples were also taken from the parents for chromosome karyotyping analysis. RESULTS: The fetal karyotype showed additional material of unknown-origin attached to Yq. Array CGH analysis confirmed that the material was derived from 3q22.1q29. The father was found to carry a balanced translocation 46, X, t(Y;3)(q12;q23) (which was diagnosed as 46,XY,Y≥18 elsewhere), whilst the mother was found to be normal. CONCLUSION: 3q partial trisomy may present as malformation of multiple systems. Combination of chromosome karyotyping and array-CGH can provide reliable diagnosis for fetuses with abnormalities by ultrasonography.


Assuntos
Cromossomos Humanos Par 3/genética , Diagnóstico Pré-Natal , Trissomia , Hibridização Genômica Comparativa , Feminino , Feto , Humanos , Cariotipagem , Masculino , Gravidez
4.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(7): 724-726, 2019 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-31302921

RESUMO

OBJECTIVE: To explore the molecular mechanism of a girl with developmental delay and intellectual disability. METHODS: Chromosomal karotypes of the child and her parents were analyzed with routine G-banding method. Their genomic DNA was also analyzed with array comparative genomic hybridization (aCGH) for chromosomal duplications/deletions. RESULTS: No karyotypic abnormality was detected in the child and her parents, while aCGH has identified a de novo 3.37 Mb deletion at 17p11.2 in the child. CONCLUSION: The child was diagnosed with Smith-Magenis syndrome, for which RAI1 may be the causative gene.


Assuntos
Síndrome de Smith-Magenis/genética , Criança , Deleção Cromossômica , Duplicação Cromossômica , Cromossomos Humanos Par 17/genética , Hibridização Genômica Comparativa , Feminino , Humanos , Cariotipagem
5.
Cytogenet Genome Res ; 158(3): 121-125, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31315107

RESUMO

VACTERL association is defined by the occurrence of congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula with esophageal atresia, radial and renal dysplasia, and limb defects. No genetic alterations have been discovered except for some sporadic chromosomal rearrangements and gene mutations. We report a boy with VACTERL association and shawl scrotum with bifid scrotum who presented with a de novo Yq11.223q11.23 microdeletion identified by array CGH. The deletion spans 3.1 Mb and encompasses several genes in the AZFc region, frequently deleted in infertile men with severe oligozoospermia or azoospermia. Herein, we discuss the possible explanation for this unusual genotype-phenotype correlation. We suggest that the deletion of the BPY2 (previously VCY2) gene, located in the AZFc region and involved in spermatogenesis, contributed to the genesis of the phenotype. In fact, BPY2 interacts with a ubiquitin-protein ligase, involved in the SHH pathway which is known to be implicated in the genesis of VACTERL association.


Assuntos
Canal Anal/anormalidades , Deleção Cromossômica , Cromossomos Humanos Y/genética , Esôfago/anormalidades , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/patologia , Rim/anormalidades , Deformidades Congênitas dos Membros/genética , Deformidades Congênitas dos Membros/patologia , Proteínas/genética , Escroto/patologia , Coluna Vertebral/anormalidades , Traqueia/anormalidades , Canal Anal/patologia , Hibridização Genômica Comparativa , Esôfago/patologia , Estudos de Associação Genética , Humanos , Lactente , Rim/patologia , Masculino , Coluna Vertebral/patologia , Traqueia/patologia , Ubiquitina-Proteína Ligases/metabolismo , Incerteza
6.
Cytogenet Genome Res ; 158(2): 63-73, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31261151

RESUMO

Terminal deletion of chromosome 4 (4q deletion syndrome) is a rare genetic condition that is characterized by a broad clinical spectrum and phenotypic variability. Diagnosis of the distinct condition can be identified by conventional chromosome analysis and small deletions by novel molecular cytogenetic methods such as microarray comparative genome hybridization (aCGH). Prenatal diagnosis is challenging; to date 10 cases have been described. We report a prenatally diagnosed case of de novo 4q deletion syndrome confirmed by conventional karyotyping and FISH due to an elevated combined risk for Down syndrome and prenatal ultrasound findings. aCGH validated the diagnosis and offered exact characterization of the disorder. Cytogenetic and microarray results described a 4q32.1qter terminal deletion of the fetus. Prenatal ultrasound detected multiple nonstructural findings (micrognathia, choroid plexus cysts, echogenic fetal bowel, short femur, and cardiac axis deviation). Pregnancy was terminated at 20 weeks. In addition to the index patient, we reviewed the 10 prenatally published cases of 4q deletion syndrome in the literature and compared these with our results. We summarize the patients' characteristics and prenatal clinical findings. Alterations of maternal serum biochemical factors, an elevated combined risk for trisomies, and distinct ultrasonographic findings can often be observed in cases of prenatal 4q deletion syndrome and may facilitate the otherwise difficult prenatal diagnosis.


Assuntos
Transtornos Cromossômicos/diagnóstico , Hibridização in Situ Fluorescente/métodos , Cariotipagem/métodos , Diagnóstico Pré-Natal/métodos , Aborto Induzido , Adulto , Deleção Cromossômica , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 4/genética , Hibridização Genômica Comparativa , Feminino , Humanos , Idade Materna , Fenótipo , Gravidez , Fatores de Risco
7.
Virchows Arch ; 475(3): 383-389, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31250201

RESUMO

Gastric hyperplastic polyps are common and generally regarded as benign lesions, whereas gastric adenocarcinomas infrequently occur from gastric hyperplastic polyps. Although gastric hyperplastic polyps have received a lot of attention because of their association with malignant transformation, it remains unclear whether gastric hyperplastic polyps are neoplastic lesions that have sporadic genetic changes similar to colorectal hyperplastic polyps. We performed genome-wide analyses of two gastric adenocarcinomas with hyperplastic polyp components. The interface between "adenocarcinoma" and "hyperplastic polyp" components was fairly sharp, and the adenocarcinoma components had copy number alterations and TP53 mutations, whereas the hyperplastic polyp components had only single nucleotide polymorphisms, which were also found in adenocarcinoma components. We did not detect any somatic changes in the hyperplastic polyp components, even in genome-wide analyses, which was in contrast to the adenocarcinoma components. However, due to the small number of cases examined herein, further genetic analyses of more cases are needed.


Assuntos
Pólipos Adenomatosos/patologia , Pólipos Intestinais/patologia , Neoplasias Gástricas/genética , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Transformação Celular Neoplásica/patologia , Hibridização Genômica Comparativa/métodos , Variações do Número de Cópias de DNA/genética , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Hiperplasia , Polimorfismo de Nucleotídeo Único/genética , Pólipos/patologia , Neoplasias Gástricas/patologia , Proteína Supressora de Tumor p53/genética
8.
Cytogenet Genome Res ; 158(1): 25-31, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31055587

RESUMO

Diagnosing a complex genetic syndrome and correctly assigning the concomitant phenotypic traits to a well-defined clinical form is often a medical challenge. In this work, we report the analysis of a family with complex phenotypes, including microcephaly, intellectual disability, dysmorphic features, and polydactyly in the proband, with the aim of adding new aspects for obtaining a clear diagnosis. We performed array-comparative genomic hybridization and quantitative reverse transcriptase PCR (qRT-PCR) analyses. We identified a deletion of chromosome 20p12.1 involving the macrodomain containing 2/mono-ADP ribosylhydrolase 2 gene (MACROD2) in several members of the family. This gene is actually not associated with a specific syndrome but with congenital anomalies of multiple organs. qRT-PCR showed higher levels of a MACROD2 mRNA isoform in the individuals carrying the deletion. Our results, together with other data reported in the literature, support the hypothesis that the deletion in MACROD2 can affect correct embryonic development and that the presence of another associated event, such as epigenetic modifications at the MACROD2 locus, can influence the level of severity of the pathology.


Assuntos
Anormalidades Múltiplas/genética , Enzimas Reparadoras do DNA/genética , Hidrolases/genética , Deficiência Intelectual/genética , Rim/anormalidades , Microcefalia/genética , Pâncreas/anormalidades , Polidactilia/genética , Deleção de Sequência , Adulto , Cromossomos Humanos Par 20/genética , Cromossomos Humanos Par 20/ultraestrutura , Hibridização Genômica Comparativa , Enzimas Reparadoras do DNA/deficiência , Enzimas Reparadoras do DNA/fisiologia , Desenvolvimento Embrionário/genética , Feminino , Humanos , Hidrolases/deficiência , Hidrolases/fisiologia , Masculino , Linhagem , Fenótipo , Transtornos Psicomotores/genética
9.
BMC Cancer ; 19(1): 412, 2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31046733

RESUMO

BACKGROUND: The SK-PN-DW cell line was established in 1979 and is commercially available. Despite the use of this cell line as an in vitro model for functional and therapeutic studies of malignant primitive neuroectodermal tumor (PNET), there is a lack of complete information about the genetic alterations that are present at the cytogenetic level. Thus, the current study aimed to characterize the cytogenetic profile of this cell line. METHODS: Routine G-banded chromosome analysis, fluorescence in situ hybridization, and oligonucleotide array comparative genomic hybridization assays were performed to characterize the chromosomal changes in this cell line. RESULTS: The G-banded karyotype analysis showed that the number of chromosomes in this cell line ranged between 36 and 41. Importantly, all cells displayed a loss of chromosomes Y, 11, 13, and 18. However, some cells showed an additional loss of chromosome 10. Additionally, the observed structural changes indicated: a) unbalanced translocation between chromosomes 1 and 7; b) translocation between chromosomes 11 and 22 at breakpoints 11q24 and 22q12, which is a classical translocation that is associated with Ewing sarcoma; c) a derivative chromosome due to a whole arm translocation between chromosomes 16 and 17 at likely breakpoints 16p10 and 17q10; and d) possible rearrangement in the short arm of chromosome 18. Moreover, a variable number of double minutes were also observed in each metaphase cell. Furthermore, the microarray assay results not only demonstrated genomic-wide chromosomal imbalance in this cell line and precisely placed chromosomal breakpoints on unbalanced, rearranged chromosomes, but also revealed information about subtle chromosomal changes and the chromosomal origin of double minutes. Finally, the fluorescence in situ hybridization assay confirmed the findings of the routine cytogenetic analysis and microarrays. CONCLUSION: The accurate determination of the cytogenetic profile of the SK-PN-DW cell line is helpful in enabling the research community to utilize this cell line for future identity and comparability studies, in addition to demonstrating the utility of the complete cytogenetic profile, as a public resource.


Assuntos
Neoplasias Encefálicas/genética , Análise Citogenética/métodos , Tumores Neuroectodérmicos Primitivos/genética , Linhagem Celular Tumoral , Bandeamento Cromossômico , Deleção Cromossômica , Hibridização Genômica Comparativa , Humanos , Hibridização in Situ Fluorescente , Cariótipo , Translocação Genética
10.
Cytogenet Genome Res ; 157(3): 135-140, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30933954

RESUMO

We report a patient with developmental delay, brachydactyly type E, short stature, and tetralogy of Fallot. Brachydactyly-mental retardation syndrome (BDMR) was suspected based on the phenotype; however, array CGH excluded a 2q37 deletion, but identified a deletion encompassing the SHOX gene. BDMR is characterized by cognitive impairment, skeletal abnormalities involving hands and feet, short stature, and overweight. Most affected individuals carry relatively large 2q37 deletions encompassing HDAC4. This gene encodes a histone deacetylase involved in epigenetic regulation of cell growth and differentiation, specifically during endochondral bone formation in chondrocyte hypertrophy. Since SHOX haploinsufficiency can cause skeletal defects and short stature but would not fully explain the clinical picture of this patient, exome sequencing was performed, and a heterozygous HDAC8 frameshift mutation was identified. HDAC8 is a distinct histone deacetylase involved in cohesin recycling and is responsible for an X-linked dominant Cornelia de Lange-like phenotype. A new blended clinical phenotype may be explained by the result of a dual molecular diagnosis, which represents a combination of 2 independent genetic defects, with relevant implications for genetic counseling, clinical management, and prognosis.


Assuntos
Síndrome de Lange/diagnóstico , Mutação da Fase de Leitura , Deleção de Genes , Transtornos do Crescimento/diagnóstico , Histona Desacetilases/genética , Osteocondrodisplasias/diagnóstico , Proteínas Repressoras/genética , Proteína de Homoeobox de Baixa Estatura/genética , Criança , Hibridização Genômica Comparativa , Síndrome de Lange/genética , Feminino , Transtornos do Crescimento/genética , Haploinsuficiência , Humanos , Osteocondrodisplasias/genética , Linhagem , Fenótipo , Sequenciamento Completo do Exoma
11.
Mol Genet Genomics ; 294(4): 1007-1022, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30968246

RESUMO

Acute hepatopancreatic necrosis disease (AHPND) is a recently discovered shrimp disease that has become a severe threat to global shrimp-farming industry. The causing agents of AHPND were identified as Vibrio parahaemolyticus and other vibrios harboring a plasmid encoding binary toxins PirAvp/PirBvp. However, the epidemiological involvement of environmental vibrios in AHPND is poorly understood. In this study, with an aim to reveal the possible transmission route of AHPND-causing V. parahaemolyticus, we sequenced and analyzed the genomes of four pairs of V. parahaemolyticus strains from four representative regions of shrimp farming in China, each including one strain isolated from diseased shrimp during an AHPND outbreak and one strain isolated from sediment before AHPND outbreaks. Our results showed that all the four shrimp-isolated and three of the sediment-isolated strains encode and secret PirAvp/PirBvp toxins and, therefore, are AHPND-causing strains. In silico multilocus sequence typing and high-resolution phylogenomic analysis based on single-nucleotide polymorphisms, as well as comparison of genomic loci in association with prophages and capsular polysaccharides (CPSs) consistently pointed to a close genetic relationship between the shrimp- and sediment-isolated strains obtained from the same region. In addition, our analyses revealed that the sequences associated with prophages, CPSs, and type VI secretion system-1 are highly divergent among strains from different regions, implying that these genes may play vital roles in environmental adaptation for AHPND-causing V. parahaemolyticus and thereby be potential targets for AHPND control. Summing up, this study provides the first direct evidence regarding the transmission route of AHPND-causing V. parahaemolyticus and underscores that V. parahaemolyticus in shrimp are most likely originated from local environment. The importance of environmental disinfection measures in shrimp farming was highlighted.


Assuntos
Toxinas Bacterianas/genética , Penaeidae/microbiologia , Vibrioses/veterinária , Vibrio parahaemolyticus/classificação , Animais , China , Hibridização Genômica Comparativa , Evolução Molecular , Genômica , Tipagem de Sequências Multilocus , Filogenia , Polimorfismo de Nucleotídeo Único , Vibrio parahaemolyticus/genética , Vibrio parahaemolyticus/isolamento & purificação , Sequenciamento Completo do Genoma
12.
Cytogenet Genome Res ; 157(4): 231-238, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30933949

RESUMO

Constitutional complex chromosomal rearrangements (CCRs) are rare events that typically involve 2 or more chromosomes with at least 3 breakpoints and can result in normal or abnormal phenotypes depending on whether they disturb the euchromatic neighborhood. Here, we report an unusual balanced CCR involving chromosomes 1, 9, and 10 that causes an unbalanced karyotype in a severely affected toddler. The CCR was initially reported as a maternal 2-way translocation but was reclassified as a 3-way translocation after a microarray analysis of the propositus revealed the involvement of another chromosome not identified by G-banding in his phenotypically normal mother. FISH assays on maternal metaphase cells confirmed that the 1qter region of der(1) was translocated to der(10), whereas the 10qter segment was translocated to der(9), which in turn donated a segment to der(1). Subsequently, this CCR was also identified in her phenotypically normal father (the patient's grandfather). Thus, the patient inherited the previously unreported pathogenic combination of der(1) with a loss of 1q43→qter (including AKT3, ZBTB18, HNRNPU, and SMYD3) and der(9) with a gain of 10q25.2→qter (including FGFR2), leading to a compound phenotype with key features of the 1q43→qter deletion and distal 10q trisomy syndromes. Our observations suggest that the loss of SMYD3 accounts for cardiac defects in a subset of patients. Moreover, due to recurrent miscarriages in this family, our findings allowed improved genetic counseling.


Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 10/genética , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 9/genética , Anormalidades Múltiplas/diagnóstico por imagem , Pré-Escolar , Hibridização Genômica Comparativa , Aconselhamento Genético , Histona-Lisina N-Metiltransferase/genética , Humanos , Hibridização in Situ Fluorescente/métodos , Masculino , Tomografia Computadorizada por Raios X , Translocação Genética
13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(5): 491-494, 2019 May 10.
Artigo em Chinês | MEDLINE | ID: mdl-31030441

RESUMO

OBJECTIVE: To provide genetic testing for two brothers with mental retardation and epilepsy. METHODS: Array comparative genomic hybridization (aCGH) was used to detect copy number variations in the two patients, their parents and maternal grandparents. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was utilized to delineate the deleted region in the pedigree. RESULTS: A 138 kb deletion in 15q11.2 region was detected by aCGH in both patients, which encompassed part of the UBE3A gene. MS-MLPA has narrowed down the region to exons 8 to 14 of the UBE3A gene. The same deletion was also found in their mother and grandfather. CONCLUSION: The pathogenesis of this rare form of recurrent Angelman syndrome may be attributed to the partial deletion of maternal UBE3A gene.


Assuntos
Síndrome de Angelman , Hibridização Genômica Comparativa , Variações do Número de Cópias de DNA , Feminino , Deleção de Genes , Humanos , Masculino , Deleção de Sequência , Ubiquitina-Proteína Ligases
14.
Anticancer Res ; 39(4): 1869-1874, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30952727

RESUMO

BACKGROUND/AIM: Chronic inflammation in end-stage kidney is associated with the development of pre-neoplastic lesions and renal cell tumors. The aim of this study was to clarify the role of the inflammatory microenvironment in this process. MATERIALS AND METHODS: We used representative microscopic slides from 11 end stage-kidneys containing pre-neoplastic lesions and tumors and applied immunohistochemistry to detect IL-6, SAA1 and LBP expression. We also applied array-based comparative genomic hybridization (CGH) analysis to detect genomic changes in tumor cells. RESULTS: We identified strong expression of IL6, LBP and SAA1 in activated stromal fibroblasts, in proliferating epithelial and tumor cells. Array CGH detected unusual genomic changes in tumor cells. CONCLUSION: Our data indicate that expression of IL6, acute phase protein SAA1 and LBP maintain a long-lasting inflammatory microenvironment that leads to remodeling of end-stage kidneys and the development of unique types of renal cell tumors.


Assuntos
Mediadores da Inflamação/análise , Interleucina-6/análise , Falência Renal Crônica/metabolismo , Neoplasias Renais/química , Rim/química , Lesões Pré-Cancerosas/metabolismo , Microambiente Tumoral , Proteínas da Fase Aguda/análise , Adulto , Idoso , Proteínas de Transporte/análise , Proliferação de Células , Hibridização Genômica Comparativa , Células Epiteliais/química , Células Epiteliais/patologia , Feminino , Fibroblastos/química , Fibroblastos/patologia , Humanos , Imuno-Histoquímica , Rim/patologia , Falência Renal Crônica/genética , Falência Renal Crônica/patologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Glicoproteínas de Membrana/análise , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Proteína Amiloide A Sérica/análise , Células Estromais/química , Células Estromais/patologia
15.
BMC Genomics ; 20(1): 181, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30845913

RESUMO

BACKGROUND: Copy number variations (CNVs) are structural variants consisting of large-scale insertions and deletions of genomic fragments. Exploring CNVs and estimating their effects on phenotypes are useful for genome selection but remain challenging in the livestock. RESULTS: We identified 1043 CNV regions (CNVRs) from array comparative genomic hybridization (CGH) data of 47 Holstein bulls. Using a probe-based CNV association approach, we detected 87 CNVRs significantly (Bonferroni-corrected P value < 0.05) associated with at least one out of 41 complex traits. Within them, 39 CNVRs were simultaneously associated with at least 2 complex traits. Notably, 24 CNVRs were markedly related to daughter pregnancy rate (DPR). For example, CNVR661 containing CYP4A11 and CNVR213 containing CTR9, respectively, were associated with DPR and other traits related to reproduction, production, and body conformation. CNVR758 was also significantly related to DPR, with a nearby gene CAPZA3, encoding one of F-actin-capping proteins which play a role in determining sperm architecture and male fertility. We corroborated these CNVRs by examining their overlapped quantitative trait loci and comparing with previously published CNV results. CONCLUSION: To our knowledge, this is one of the first genome-wide association studies based on CNVs called by array CGH in Holstein cattle. Our results contribute substantial information about the potential CNV impacts on reproduction, health, production, and body conformation traits, which lay the foundation for incorporating CNV into the future dairy cattle breeding program.


Assuntos
Bovinos/genética , Bovinos/fisiologia , Hibridização Genômica Comparativa , Variações do Número de Cópias de DNA , Reprodução/genética , Animais , Masculino
16.
Int J Mol Sci ; 20(7)2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30925701

RESUMO

Canine carcinomas have been considered natural models for human diseases; however, the genomic profile of canine prostate cancers (PCs) has not been explored. In this study, 14 PC androgen-receptor-negative cases, 4 proliferative inflammatory atrophies (PIA), and 5 normal prostate tissues were investigated by array-based comparative genomic hybridization (aCGH). Copy number alterations (CNAs) were assessed using the Canine Genome CGH Microarray 4 × 44K (Agilent Technologies). Genes covered by recurrent CNAs were submitted to enrichment and cross-validation analysis. In addition, the expression levels of TP53, MDM2 and ZBTB4 were evaluated in an independent set of cases by qPCR. PC cases presented genomic complexity, while PIA samples had a small number of CNAs. Recurrent losses covering well-known tumor suppressor genes, such as ATM, BRCA1, CDH1, MEN1 and TP53, were found in PC. The in silico functional analysis showed several cancer-related genes associated with canonical pathways and interaction networks previously described in human PC. The MDM2, TP53, and ZBTB4 copy number alterations were translated into altered expression levels. A cross-validation analysis using The Cancer Genome Atlas (TCGA) database for human PC uncovered similarities between canine and human PCs. Androgen-receptor-negative canine PC is a complex disease characterized by high genomic instability, showing a set of genes with similar alterations to human cancer.


Assuntos
Doenças do Cão/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata/veterinária , Receptores Androgênicos/genética , Transcriptoma , Animais , Hibridização Genômica Comparativa , Variações do Número de Cópias de DNA , Cães , Instabilidade Genômica , Genômica , Masculino , Neoplasias da Próstata/genética , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteína Supressora de Tumor p53/genética
17.
Int J Mol Sci ; 20(5)2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30871102

RESUMO

A collection of intracranial astrocytomas of different malignancy grades was analyzed for copy number aberrations (CNA) in order to identify regions that are driving cancer pathogenesis. Astrocytomas were analyzed by Array Comparative Genomic Hybridization (aCGH) and bioinformatics utilizing a Bioconductor package, Genomic Identification of Significant Targets in Cancer (GISTIC) 2.0.23 and DAVID software. Altogether, 1438 CNA were found of which losses prevailed. On our total sample, significant deletions affected 14 chromosomal regions, out of which deletions at 17p13.2, 9p21.3, 13q12.11, 22q12.3 remained significant even at 0.05 q-value. When divided into malignancy groups, the regions identified as significantly deleted in high grades were: 9p21.3; 17p13.2; 10q24.2; 14q21.3; 1p36.11 and 13q12.11, while amplified were: 3q28; 12q13.3 and 21q22.3. Low grades comprised significant deletions at 3p14.3; 11p15.4; 15q15.1; 16q22.1; 20q11.22 and 22q12.3 indicating their involvement in early stages of tumorigenesis. Significantly enriched pathways were: PI3K-Akt, Cytokine-cytokine receptor, the nucleotide-binding oligomerization domain (NOD)⁻like receptor, Jak-STAT, retinoic acid-inducible gene (RIG)-I-like receptor and Toll-like receptor pathways. HPV and herpex simplex infection and inflammation pathways were also represented. The present study brings new data to astrocytoma research amplifying the wide spectrum of changes that could help us identify the regions critical for tumorigenesis.


Assuntos
Astrocitoma/genética , Astrocitoma/patologia , Variações do Número de Cópias de DNA/genética , Adulto , Idoso , Carcinogênese/genética , Carcinogênese/patologia , Aberrações Cromossômicas , Hibridização Genômica Comparativa/métodos , Feminino , Genômica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/genética , Adulto Jovem
18.
Int J Mol Sci ; 20(5)2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30836598

RESUMO

Chromosome 16 is one of the most gene-rich chromosomes of our genome, and 10% of its sequence consists of segmental duplications, which give instability and predisposition to rearrangement by the recurrent mechanism of non-allelic homologous recombination. Microarray technologies have allowed for the analysis of copy number variations (CNVs) that can contribute to the risk of developing complex diseases. By array comparative genomic hybridization (CGH) screening of 1476 patients, we detected 27 cases with CNVs on chromosome 16. We identified four smallest regions of overlapping (SROs): one at 16p13.11 was found in seven patients; one at 16p12.2 was found in four patients; two close SROs at 16p11.2 were found in twelve patients; finally, six patients were found with atypical rearrangements. Although phenotypic variability was observed, we identified a male bias for Childhood Apraxia of Speech associated to 16p11.2 microdeletions. We also reported an elevated frequency of second-site genomic alterations, supporting the model of the second hit to explain the clinical variability associated with CNV syndromes. Our goal was to contribute to the building of a chromosome 16 disease-map based on disease susceptibility regions. The role of the CNVs of chromosome 16 was increasingly made clear in the determination of developmental delay. We also found that in some cases a second-site CNV could explain the phenotypic heterogeneity by a simple additive effect or a pejorative synergistic effect.


Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 16/genética , Hibridização Genômica Comparativa , Deficiências do Desenvolvimento/genética , Anormalidades Múltiplas/classificação , Anormalidades Múltiplas/fisiopatologia , Adolescente , Adulto , Criança , Pré-Escolar , Aberrações Cromossômicas , Deleção Cromossômica , Variações do Número de Cópias de DNA/genética , Deficiências do Desenvolvimento/classificação , Deficiências do Desenvolvimento/fisiopatologia , Feminino , Recombinação Homóloga/genética , Humanos , Lactente , Recém-Nascido , Cariótipo , Masculino , Fenótipo , Duplicações Segmentares Genômicas/genética , Adulto Jovem
19.
Orv Hetil ; 160(13): 484-493, 2019 Mar.
Artigo em Húngaro | MEDLINE | ID: mdl-30907100

RESUMO

Invasive prenatal testing and conventional G-banding chromosome analysis have been considered to be the gold standard of fetal cytogenetic diagnosis. Standard karyotyping is, however, constrained by the limits of the resolution of using a microscope. The advantage of molecular karyotyping, array based methods is the evaluation of sub-microscopic copy number changes across the whole genome in a single analysis. The application of array comparative genome hybridization has greatly increased the detection of pathogenic chromosomal abnormalities in prenatal settings. Based on available data in the international literature of the last decade, the clinical utility of arrayCGH is the recognition of some 1-2% and 5-7% additional genetical information compared to metaphase karyotype alone in fetuses without ultrasound anomaly and in fetuses with ultrasonographically detected malformations, respectively. Thus arrayCGH improves the prenatal diagnosis of genetic abnormalities mainly in fetuses with structural sonographic findings. In the present paper we review the literature of chromosomal microarray and make a proposal for the application of the method in Hungarian prenatal genetical practice. Orv Hetil. 2019; 160(13): 484-493.


Assuntos
Transtornos Cromossômicos/diagnóstico , Hibridização Genômica Comparativa/métodos , Análise em Microsséries/métodos , Diagnóstico Pré-Natal/métodos , Feminino , Humanos , Hungria , Cariotipagem , Gravidez
20.
Taiwan J Obstet Gynecol ; 58(2): 239-243, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30910146

RESUMO

OBJECTIVE: The primary objective of this study was to investigate whether preimplantation genetic testing for aneuploidy (PGT-A) of blastocysts through array comparative genomic hybridization (aCGH) improves live birth rates (LBR) in IVF cycles for patients with high prevalence of aneuploidy. MATERIALS AND METHODS: This study included 1389 blastocysts with aCGH results derived from 296 PGT-A cycles in IVF patients with advanced maternal age (AMA) (n = 87, group A), those with repeated implantation failure (RIF) (n = 82, group B), those with recurrent miscarriage (RM) (n = 82, group C), and oocyte donors (OD) (n = 45, young age, as a control group). Another 61 AMA patients without PGT-A procedures were used as a control group for group A. Vitrification was performed after blastocyst biopsy, and thawed euploid embryos were transferred in a nonstimulated cycle. RESULTS: For the AMA group, a significant increase in LBRs was found in the PGT-A group compared with the non-PGT-A group (54.1% vs. 32.8%, p = 0.018). Consistent LBRs (54.1%, 51.6%, 55.9%, and 57.1%, respectively, in group A, B, C, and young age group) were obtained for all the indications. CONCLUSIONS: LBRs can be improved using PGT-A of blastocysts with aCGH in IVF cycles for patients with a high rate of aneuploidy, especially for patients with AMA.


Assuntos
Aneuploidia , Coeficiente de Natalidade , Fertilização In Vitro/métodos , Testes Genéticos/métodos , Diagnóstico Pré-Implantação/métodos , Aborto Habitual/genética , Adulto , Estudos de Casos e Controles , Hibridização Genômica Comparativa , Transferência Embrionária/efeitos adversos , Transferência Embrionária/métodos , Transferência Embrionária/estatística & dados numéricos , Feminino , Fertilização In Vitro/estatística & dados numéricos , Humanos , Idade Materna , Gravidez , Estudos Retrospectivos , Falha de Tratamento
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