RESUMEN
DNA-hypomethylating agents (HMAs) induce notable remission rates in AML/MDS patients with TP53 mutations; however, secondary resistance often develops rapidly. In the DECIDER trial (NCT00867672), elderly AML patients (also those with adverse genetics) randomized to all-trans retinoic acid (ATRA) added to decitabine (DEC) attained significantly delayed time-to-resistance. An 82-year-old patient with a non-disruptive, in-frame TP53 mutation (p.Cys238_Asn239delinsTyr, VAF 90%) and complex-monosomal karyotype attained a complete hematologic and cytogenetic remission with DEC + ATRA, with 3.7 years survival after 30 treatment cycles that were well-tolerated. Further HMA + ATRA studies appear warranted in AML/MDS patients of different genetic risk groups ineligible for more intensive treatment.Trial registration: This trial was registered at ClinicalTrials.gov identifier: NCT00867672.
Asunto(s)
Decitabina , Leucemia Mieloide Aguda , Inducción de Remisión , Tretinoina , Proteína p53 Supresora de Tumor , Humanos , Decitabina/uso terapéutico , Decitabina/administración & dosificación , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Anciano de 80 o más Años , Tretinoina/uso terapéutico , Inducción de Remisión/métodos , Proteína p53 Supresora de Tumor/genética , Mutación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Masculino , Cariotipo , FemeninoRESUMEN
Brontispa longissima is a highly destructive pest that affects coconut and ornamental palm plants. It is widely distributed across Southeast and East Asia and the Pacific region, causing production losses of up to 50-70%. While control methods and ecological phenomena have been the primary focus of research, there is a significant lack of studies on the molecular mechanisms underlying these ecological phenomena. The absence of a reference genome has also hindered the development of new molecular-targeted control technologies. In this study, we conducted a karyotype analysis of B. longissima and assembled the first high-quality chromosome-level genome. The assembled genome is 582.24 Mb in size, with a scaffold N50 size of 63.81 Mb, consisting of 10 chromosomes and a GC content of 33.71%. The BUSCO assessment indicated a completeness estimate of 98.1%. A total of 23,051 protein-coding genes were predicted. Our study provides a valuable genomic resource for understanding the mechanisms of adaptive evolution and facilitates the development of new molecular-targeted control methods for B. longissima.
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Composición de Base , Animales , CariotipoRESUMEN
Multiple sex chromosomes usually arise from chromosomal rearrangements which involve ancestral sex chromosomes. There is a fundamental condition to be met for their long-term fixation: the meiosis must function, leading to the stability of the emerged system, mainly concerning the segregation of the sex multivalent. Here, we sought to analyze the degree of differentiation and meiotic pairing properties in the selected fish multiple sex chromosome system present in the wolf-fish Hoplias malabaricus (HMA). This species complex encompasses seven known karyotype forms (karyomorphs) where the karyomorph C (HMA-C) exhibits a nascent XY sex chromosomes from which the multiple X1X2Y system evolved in karyomorph HMA-D via a Y-autosome fusion. We combined genomic and cytogenetic approaches to analyze the satellite DNA (satDNA) content in the genome of HMA-D karyomorph and to investigate its potential contribution to X1X2Y sex chromosome differentiation. We revealed 56 satDNA monomers of which the majority was AT-rich and with repeat units longer than 100 bp. Seven out of 18 satDNA families chosen for chromosomal mapping by fluorescence in situ hybridization (FISH) formed detectable accumulation in at least one of the three sex chromosomes (X1, X2 and neo-Y). Nine satDNA monomers showed only two hybridization signals limited to HMA-D autosomes, and the two remaining ones provided no visible FISH signals. Out of seven satDNAs located on the HMA-D sex chromosomes, five mapped also to XY chromosomes of HMA-C. We showed that after the autosome-Y fusion event, the neo-Y chromosome has not substantially accumulated or eliminated satDNA sequences except for minor changes in the centromere-proximal region. Finally, based on the obtained FISHpatterns, we speculate on the possible contribution of satDNA to sex trivalent pairing and segregation.
Asunto(s)
Characiformes , ADN Satélite , Hibridación Fluorescente in Situ , Cromosomas Sexuales , Animales , ADN Satélite/genética , Cromosomas Sexuales/genética , Masculino , Characiformes/genética , Femenino , Evolución Molecular , Meiosis/genética , Cariotipo , Cromosoma Y/genéticaRESUMEN
Morabine grasshoppers in the Vandiemenella viatica species group, which show karyotype diversity, have been studied for their ecological distribution and speciation in relation to their genetic and chromosomal diversity. They are good models for studying sex chromosome evolution as "old" and newly emerged sex chromosomes co-exist within the group. Here we present a reference genome for the viatica19 chromosomal race, that possesses the ancestral karyotype within the group. Using PacBio HiFi and Hi-C sequencing, we generated a chromosome-level assembly of 4.09 Gb in span, scaffold N50 of 429 Mb, and complete BUSCO score of 98.1%, containing 10 pseudo-chromosomes. We provide Illumina datasets of males and females, used to identify the X chromosome. The assembly contains 19,034 predicted protein-coding genes, and a total of 75.21% of repetitive DNA sequences. By leveraging HiFi reads, we mapped the genome-wide distribution of methylated bases (5mC and 6 mA). This comprehensive assembly offers a robust reference for morabine grasshoppers and supports further research into speciation and sex chromosome diversification within the group and its related species.
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Genoma de los Insectos , Saltamontes , Saltamontes/genética , Animales , Masculino , Femenino , Cromosomas de Insectos/genética , CariotipoRESUMEN
BACKGROUND: The genus Pulmonaria (Boraginaceae) represents a taxonomically complex group of species in which morphological similarity contrasts with striking karyological variation. The presence of different numbers of chromosomes in the diploid state suggests multiple hybridization/polyploidization events followed by chromosome rearrangements (dysploidy). Unfortunately, the phylogenetic relationships and evolution of the genome, have not yet been elucidated. Our study focused on the P. officinalis group, the most widespread species complex, which includes two morphologically similar species that differ in chromosome number, i.e. P. obscura (2n = 14) and P. officinalis (2n = 16). Ornamental cultivars, morphologically similar to P. officinalis (garden escapes), whose origin is unclear, were also studied. Here, we present a pilot study on genome size and repeatome dynamics of these closely related species in order to gain new information on their genome and chromosome structure. RESULTS: Flow cytometry confirmed a significant difference in genome size between P. obscura and P. officinalis, corresponding to the number of chromosomes. Genome-wide repeatome analysis performed on genome skimming data showed that retrotransposons were the most abundant repeat type, with a higher proportion of Ty3/Gypsy elements, mainly represented by the Tekay lineage. Comparative analysis revealed no species-specific retrotransposons or striking differences in their copy number between the species. A new set of chromosome-specific cytogenetic markers, represented by satellite DNAs, showed that the chromosome structure in P. officinalis was more variable compared to that of P. obscura. Comparative karyotyping supported the hybrid origin of putative hybrids with 2n = 15 collected from a mixed population of both species and outlined the origin of ornamental garden escapes, presumably derived from the P. officinalis complex. CONCLUSIONS: Large-scale genome size analysis and repeatome characterization of the two morphologically similar species of the P. officinalis group improved our knowledge of the genome dynamics and differences in the karyotype structure. A new set of chromosome-specific cytogenetic landmarks was identified and used to reveal the origin of putative hybrids and ornamental cultivars morphologically similar to P. officinalis.
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Cromosomas de las Plantas , Genoma de Planta , Cariotipificación , Cromosomas de las Plantas/genética , Pulmonaria/genética , Tamaño del Genoma , Filogenia , CariotipoRESUMEN
The genus Stylosanthes has economic importance in semi-arid regions and requires studies that reveal complex relationships between species involving different ploidies. The aim of this study was to cytogenetically investigate accessions of Stylosanthes identified as S. scabra, in order to properly identify the number, morphology, and pattern of distribution of heterochromatin, analyzing the karyological variability of these species. Accessions with 2n=40 and 2n=20 were identified, exhibiting semi-reticulate interphase nuclei, symmetric karyotype, varied morphology, with differences in average chromosomal size, and genome length. The analysis with the fluorochromes chromomycin (CMA) and 4',6-diamidino-2-phenylindole (DAPI) allowed the visualization of two CMA+ blocks in the subterminal region of the short arm in all accessions, and DAPI+/CMA- bands in S. scabra accessions. This suggests that not only chromosomal rearrangements, but also changes in the composition of heterochromatin, may have occurred during the speciation of this genus, and that S. scabra may be undergoing chromosomal evolution based on the observed karyological differences. In addition to the ploidy level, the distribution pattern of CMA+ heterochromatin reinforces the separation between S. scabra and S. seabrana. Thus, this genus represents an interesting group of plants for further studies on the content and quantity of repetitive and non-repetitive DNA sequences.
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Cromosomas de las Plantas , Heterocromatina , Heterocromatina/genética , Cromosomas de las Plantas/genética , Cariotipo , Cariotipificación , IndolesRESUMEN
OBJECTIVE: We present mosaic distal 13q duplication due to mosaic unbalanced translocation 46,XY,der(14)t(13;14)(q32.2;p13)/46,XY at amniocentesis in a pregnancy associated with a favorable fetal outcome. CASE REPORT: A 37-year-old, gravida 2, para 0, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY, add(14) (p13)[17]/46,XY[13] (56.6% mosaicism). Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed arr 13q32.2q34 × 2â¼3, consistent with 45% mosaicism for distal 13q duplication. Repeat amniocentesis at 24 weeks of gestation revealed a karyotype of 46,XY,der(14)t(13;14)(q32.2;p13)[14]/46,XY[16] (46.6% mosaicism). The parental karyotypes were normal. aCGH analysis on the DNA extracted from uncultured amniocytes revealed arr 13q32.2q34 × 2.38, consistent with 30-40% mosaicism for distal 13q duplication. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes detected 22.8% (23/101 cells) mosaicism for distal 13q duplication. Prenatal ultrasound findings were unremarkable. At 39 weeks of gestation, a 3616-g phenotypically normal baby was delivered. The karyotypes of cord blood, umbilical cord and placenta were 46,XY,der(14)t(13;14)(q32.2;p13)[20]/46,XY[20] (50% mosaicism), 46,XY,der(14)t(13;14)(q32.2;p13)[14]/46,XY[26] (35% mosaicism) and 46,XY (40/40 cells) (0% mosaicism), respectively. When follow-ups at the age of 4½ months and the age of one year, the peripheral blood had the karyotype of 46,XY,der(14)t(13;14)(q32.2;p13)[18]/46,XY[22] (45% mosaicism). Interphase FISH analysis on buccal mucosal cells at the age of 4½ months revealed 2.7% (3/110 cells) mosaicism for distal 13q duplication, compared with 1% (1/100 cells) in the normal control. The neonate was normal in phenotype and development. CONCLUSIONS: Mosaic unbalanced translocation at amniocentesis can be associated with a favorable fetal outcome, perinatal progressive decrease of the aneuploid cell line and cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes.
Asunto(s)
Amniocentesis , Cromosomas Humanos Par 13 , Mosaicismo , Translocación Genética , Humanos , Femenino , Embarazo , Mosaicismo/embriología , Adulto , Translocación Genética/genética , Cromosomas Humanos Par 13/genética , Hibridación Genómica Comparativa , Cromosomas Humanos Par 14/genética , Cariotipificación , Aneuploidia , Trisomía/genética , Cariotipo , Resultado del Embarazo/genética , Duplicación Cromosómica/genética , Hibridación Fluorescente in SituRESUMEN
BACKGROUND: Approximately one person in 1000 is a Robertsonian translocation carrier. Errors in the formation of eggs (or more rarely of sperms) may be the cause of Robertsonian translocation. Most Robertsonian translocation carriers are healthy and have a normal lifespan, but do have an increased risk of offsprings with trisomies and pregnancy loss. The fitness of Robertsonian translocation carriers is reduced, but can provide material for evolution. MATERIALS AND METHODS: We have done prenatal diagnosis and molecular cytogenetic analyses on this homozygous Robertson translocation family. We report a homozygous Robertson translocation family with previously undescribed mosaic Robertsonian fission karyotype. RESULTS: We identified six Robertsonian translocation carriers in this family. Four were heterozygous translocation carriers of 45,XX or XY,der(14;15)(q10;q10), one was a homozygous translocation carrier of a 44,XY,der(14;15)(q10;q10),der(14;15)(q10;q10), and one was a previously undescribed Robertsonian fission carrier of 45,XN,der(14;15)(q10;q10)[42]/46,XN[58] with normal phenotype. CONCLUSION: We reported a previously undescribed mosaic Robertsonian fission karyotype. The homozygosity of Robertsonian translocation for speciation may be a potential mechanism of speciation in humans. In theory, the carriers of homologous Robertsonian translocation cannot produce normal gametes, but Robertson fission made it possible for them to produce normal gametes.
Asunto(s)
Homocigoto , Mosaicismo , Diagnóstico Prenatal , Translocación Genética , Humanos , Femenino , Masculino , Diagnóstico Prenatal/métodos , Embarazo , Cariotipo , Análisis Citogenético/métodos , Adulto , Linaje , Cariotipificación , Cromosomas Humanos Par 14/genéticaRESUMEN
OBJECTIVES: Lymphedema (LD) in Turner syndrome (TS) is a commonly reported comorbidity, though its associations with karyotype and other comorbidities are poorly understood. Characteristics of patients with TS and LD, including correlation with phenotype and karyotype, are described. METHODS: Medical records of patients with TS seen in two pediatric institutions from 2002 to 2020 were retrospectively reviewed. Demographic data (age, presentation onset, clinical features, genetics, LD presence, investigations, treatments) were collected. RESULTS: 393 girls with TS with mean age of 12.5 years (SD: 5.7) were identified. LD was noted in 37â¯% of patients (n=146). Among the 112 patients with TS and documentation of onset of LD, LD was noted within the first year of life in 78.6â¯% (n=88). 67.6â¯% (n=96) of total patients with TS and LD had non-mosaic 45, X karyotype. Frequency of webbed neck was significantly greater in girls with TS and LD compared with girls without LD (58 vs. 7â¯%, p<0.001). Congenital heart anomalies, hypertension, and renal anomalies were also more common in girls with LD. Nail abnormalities with presence of hypoplastic or dysplastic nails were significantly associated with LD (OR: 6.784, 95â¯% CI 4.235-11.046). The number of girls reporting presence of LD decreased with age. CONCLUSIONS: LD in TS often occurs within the first year of life, is less prevalent in older children and adolescents, and is significantly associated with 45, X karyotype, presence of webbed neck, nail changes, congenital heart anomalies, and renal anomalies.
Asunto(s)
Cariotipo , Linfedema , Fenotipo , Síndrome de Turner , Humanos , Síndrome de Turner/complicaciones , Síndrome de Turner/genética , Femenino , Linfedema/etiología , Linfedema/genética , Linfedema/epidemiología , Linfedema/patología , Niño , Estudios Retrospectivos , Adolescente , Pronóstico , Preescolar , Estudios de Seguimiento , Lactante , ComorbilidadRESUMEN
The eukaryotic cell division machinery must rapidly and reproducibly duplicate and partition the cell's chromosomes in a carefully coordinated process. However, chromosome numbers vary dramatically between genomes, even on short evolutionary timescales. We sought to understand how the mitotic machinery senses and responds to karyotypic changes by using a series of budding yeast strains in which the native chromosomes have been successively fused. Using a combination of cell biological profiling, genetic engineering and experimental evolution, we show that chromosome fusions are well tolerated up until a critical point. Cells with fewer than five centromeres lack the necessary number of kinetochore-microtubule attachments needed to counter outward forces in the metaphase spindle, triggering the spindle assembly checkpoint and prolonging metaphase. Our findings demonstrate that spindle architecture is a constraining factor for karyotype evolution.
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Cinetocoros , Saccharomyces cerevisiae , Huso Acromático , Huso Acromático/metabolismo , Huso Acromático/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Cinetocoros/metabolismo , Cariotipo , Cromosomas Fúngicos/genética , Mitosis/genética , Evolución Molecular , Microtúbulos/metabolismo , Centrómero/genética , Centrómero/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMEN
MAIN CONCLUSION: Allotetraploid wheat reflects evolutionary divergence and domestication convergence in the karyotypic and phenotypic evolution, accompanied with the transformation from r- strategy to K- strategy in reproductive fitness. Allotetraploid wheat, the progenitor of hexaploidy bread wheat, has undergone 300,000 years of natural evolution and 10,000 years of domestication. The variations in karyotype and phenotype as well as fertility fitness have not been systematically linked. Here, by combining fluorescent in situ hybridization with the quantification of phenotypic and reproductive traits, we compared the karyotype, vegetative growth phenotype and reproductive fitness among synthesized, wild and domesticated accessions of allotetraploid wheat. We detected that the wild accessions showed dramatically high frequencies of homologous recombination and copy number variations of simple sequence repeats (SSR) comparing with synthetic and domesticated accessions. The phenotypic traits reflected significant differences among the populations shaped by distinct evolutionary processes. The diversity observed in wild accessions was significantly greater than that in domesticated ones, particularly in traits associated with vegetative growth and spike morphology. We found that the active pollen of domesticated accessions exhibited greater potential of germination, despite a lower rate of active pollen compared with the wild accessions, indicating a transformation in reproductive fitness strategy for pollen development in domesticated accessions compared to the wild accessions, from r-strategy to K-strategy. Our results demonstrate the condensation of karyotype and phenotype from natural wild accessions to domesticated accessions in allotetraploid wheats. Ecological strategy transformation should be seriously considered from evolution to domestication in polyploid plants, especially crops, which may provide a perspective on the adaptive evolution of polyploid plants.
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Domesticación , Fenotipo , Tetraploidía , Triticum , Triticum/genética , Triticum/crecimiento & desarrollo , Triticum/fisiología , Evolución Biológica , Cariotipo , Reproducción/genética , Polen/genética , Polen/crecimiento & desarrollo , Repeticiones de Microsatélite/genética , Hibridación Fluorescente in Situ , Variaciones en el Número de Copia de ADN/genéticaRESUMEN
OBJECTIVE: To investigate the clinical and genetic characteristics of a male carrier of exceptional complex chromosome rearrangement (CCR) and the outcome of preimplantation genetic testing for chromosomal structural rearrangement (PGT-SR). METHODS: Using the modified high resolution G banding technique and whole-genome low-coverage sequencing (WGLCS), we analyzed the cellular karyotype and molecular karyotype of a male carrier of CCR, performed an analysis of the single-sperm chromosome copy number and conducted PGT-SR for the patient by next-generation sequencing (NGS). In addition, we reviewed the literature on reported male carriers of CCRs and summarized their normal/balanced sperm ratios and PGT-SR outcomes. RESULTS: The karyotype of the patient was 46,XY,der(5)inv(5)(q14.3q23.2)t(5;14;11) (q23.2;q31.1;q21),der(11)t(5;14;11);der(14)t(5;14;11), with the translocation breakpoints located in the intergenic region. Single-sperm sequencing revealed 20.0%ï¼7/35ï¼of normal haploids in the male's spermatozoaï¼ and the results PGT-SR showed a proportion of 25.0%ï¼4/16ï¼of normal/balanced embryos. After thawing and transferring of 2 euploid blastocysts, a healthy male infant was successfully delivered. CONCLUSION: The proportion of normal haploids in the spermatozoa of male CCR carriers may be higher than theoretically predicted, and PGT-SR can effectively improve the pregnancy outcome in male CCR carriers and provide valuable data for genetic counseling.
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Diagnóstico Preimplantación , Translocación Genética , Humanos , Masculino , Diagnóstico Preimplantación/métodos , Femenino , Cariotipificación , Embarazo , Espermatozoides , Adulto , Pruebas Genéticas , Heterocigoto , Aberraciones Cromosómicas , Cariotipo , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
Goats are considered the leading farm animal that has a substantial role in the agricultural sector in the Kurdistan Region of Iraq. No cytological examination has been carried out on them. This experiment aims to identify the Karyotype of the local breeds of domestic goats. This experiment was conducted on the Karyotype and prepared the ideogram of Meriz goats. The determination of the relative length and centromeric index arm ratio of the chromosomes in the breed was achieved by the production of karyotypes. A total of (30)Meriz goats, consisting of (10) males and (20) females, were selected to collect blood samples for a short-term lymphocyte culture. The diploid chromosome count was observed to be (60), consisting of (29) pairs of acrocentric autosomes and one pair of allosomes, specifically the X and Y chromosomes. The acrocentric nature of the X-chromosome and the sub-metacentric nature of the Y-chromosome were identified through scientific investigation. The study observed a variation in the relative length of autosomal chromosomes in Meriz goats, with females ranging from 4.49% to 1.89% and males ranging from (4.53%) to (1.75%). The X-chromosome had a relative length of 3.96 in females, while the Y-chromosome displayed a relative length of (5.05). The findings of this karyological investigation suggest that the chromosomal composition seen in the Meriz goats under examination was within the expected range of normalcy. It is recommended that more cytogenetic analyses be conducted at the population level in order to identify individuals within the Meriz breed population who possesses numerical and/or structural chromosome abnormalities. This research is crucial for enhancing the efficiency of production and reproduction in this breed.
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Cruzamiento , Cabras , Cariotipificación , Animales , Cabras/genética , Femenino , Irak , Masculino , Cariotipo , Análisis Citogenético , Cromosoma Y/genética , Cromosoma X/genéticaRESUMEN
The genus Rhinella corresponds to a group of anurans characterized by numerous taxonomic and systemic challenges, leading to their organization into species complexes. Cytogenetic data for this genus thus far are limited to the diploid number and chromosome morphology, which remain highly conserved among the species. In this study, we analyse the karyotypes of three species of the genus Rhinella (Rhinella granulosa, Rhinella margaritifera, and Rhinella marina) using both classical (conventional staining and C-banding) and molecular (FISH-fluorescence in situ hybridization with 18S rDNA, telomeric sequences, and microsatellite probes) cytogenetic approaches. The aim of this study is to provide data that can reveal variations in the distribution of repetitive sequences that can contribute to understanding karyotypic diversification in these species. The results revealed a conserved karyotype across the species, with 2n = 22 and FN = 44, with metacentric and submetacentric chromosomes. C-banding revealed heterochromatic blocks in the pericentromeric region for all species, with a proximal block on the long arms of pairs 3 and 6 in R. marina and on the short arms of pairs 4 and 6 in R. margaritifera. Additionally, 18S rDNA probes hybridized to pair 5 in R. granulosa, to pair 7 in R. marina, and to pair 10 in R. margaritifera. Telomeric sequence probes displayed signals exclusively in the distal region of the chromosomes, while microsatellite DNA probes showed species-specific patterns. These findings indicate that despite a conserved karyotypical macrostructure, chromosomal differences exist among the species due to the accumulation of repetitive sequences. This variation may be attributed to chromosome rearrangements or differential accumulation of these sequences, highlighting the dynamic role of repetitive sequences in the chromosomal evolution of Rhinella species. Ultimately, this study emphasizes the importance of the role of repetitive DNAs in chromosomal rearrangements to elucidate the evolutionary mechanisms leading to independent diversification in the distinct phylogenetic groups of Rhinella.
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Análisis Citogenético , Hibridación Fluorescente in Situ , Cariotipo , Repeticiones de Microsatélite , Animales , Repeticiones de Microsatélite/genética , Bufonidae/genética , Bufonidae/clasificación , Femenino , ARN Ribosómico 18S/genética , Telómero/genética , Especificidad de la Especie , Bandeo Cromosómico , Cariotipificación , Masculino , ADN Ribosómico/genéticaRESUMEN
Pure erythroid leukemia (PEL) is an extremely rare subtype of acute myeloid leukemia (AML). Although not specific, PEL is almost uniformly associated with complex karyotype and TP53 mutations. Given the rarity of the disease, our understanding of its cytogenetic and molecular features deems incomplete. We aim to complement existing literature by presenting an unusual case of PEL. The case is comprehensively worked up with multiple modalities. We present for the first time a case of PEL with unusual cytogenetic and molecular features: normal karyotype with absence of TP53 mutations and presence of NPM1 and NRAS mutations. This is a valuable addition to literature, expanding our understanding of molecular and cytogenetic spectra of PEL.
Asunto(s)
Leucemia Eritroblástica Aguda , Mutación , Proteínas Nucleares , Nucleofosmina , Humanos , Proteínas Nucleares/genética , Leucemia Eritroblástica Aguda/genética , Leucemia Eritroblástica Aguda/diagnóstico , Leucemia Eritroblástica Aguda/patología , Cariotipo , Masculino , Proteína p53 Supresora de Tumor/genética , Femenino , Persona de Mediana EdadRESUMEN
OBJECTIVES: 45,X/46,XY mosaicism is a rare condition with clinical and genetic heterogeneity and have a greatly increased risk of developing germ cell tumors. We describe a rare 45,X/46,XY Chinese girl with malignant tumors, especially focusing on the molecular genetics of gonadal tumor. CASE PRESENTATION: We report a phenotypically Turner-like Chinese adolescent girl who presented primary amenorrhea and a pelvic mass as the chief complaint, which finally demonstrated dysgerminoma replacing the left gonad and gonadoblastoma arising from right gonad respectively. Her chromosome karyotype was 45,X(4)/46,XY(46); Y-chromosome microdeletions in AZFb regions were found on gonadal DNA rather than peripheral blood lymphocyte (PBL) DNA, while no variants were found in the promoter and coding region of SRY gene in both PBL and gonadal tissues. She underwent bilateral gonadectomy; no recurrence or serious complications were identified after 3 years of follow-up. CONCLUSIONS: This case emphasizes the probable correlation between Y chromosome microdeletions in gonadal tissue and the severity of the phenotype in patients with 45,X/46,XY mosaicism and highlights the importance of clinical genetic testing at the chromosomal and molecular level.
Asunto(s)
Disgerminoma , Gonadoblastoma , Neoplasias Ováricas , Fenotipo , Síndrome de Turner , Humanos , Femenino , Gonadoblastoma/genética , Gonadoblastoma/patología , Gonadoblastoma/cirugía , Disgerminoma/genética , Disgerminoma/patología , Disgerminoma/cirugía , Adolescente , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Síndrome de Turner/genética , Síndrome de Turner/patología , Síndrome de Turner/complicaciones , Mosaicismo , Pronóstico , Cariotipo , Proteína de la Región Y Determinante del Sexo/genética , Pueblos del Este de AsiaRESUMEN
Karyotypes, composed of chromosomes, must be accurately partitioned by the mitotic spindle for optimal cell health. However, it is unknown how underlying characteristics of karyotypes, such as chromosome number and size, govern the scaling of the mitotic spindle to ensure accurate chromosome segregation and cell proliferation. We utilize budding yeast strains engineered with fewer chromosomes, including just two "mega chromosomes," to study how spindle size and function are responsive to, and scaled by, karyotype. We determined that deletion and overexpression of spindle-related genes are detrimental to the growth of strains with two chromosomes, suggesting that mega chromosomes exert altered demands on the spindle. Using confocal microscopy, we demonstrate that cells with fewer but longer chromosomes have smaller spindle pole bodies, fewer microtubules, and longer spindles. Moreover, using electron tomography and confocal imaging, we observe elongated, bent anaphase spindles with fewer core microtubules in strains with mega chromosomes. Cells harboring mega chromosomes grow more slowly, are delayed in mitosis, and a subset struggle to complete chromosome segregation. We propose that the karyotype of the cell dictates the microtubule number, type, spindle pole body size, and spindle length, subsequently influencing the dynamics of mitosis, such as the rate of spindle elongation and the velocity of pole separation. Taken together, our results suggest that mitotic spindles are highly plastic ultrastructures that can accommodate and adjust to a variety of karyotypes, even within a species.
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Saccharomyces cerevisiae , Huso Acromático , Huso Acromático/metabolismo , Saccharomyces cerevisiae/genética , Microtúbulos/metabolismo , Segregación Cromosómica , Mitosis , Cromosomas Fúngicos/genética , CariotipoRESUMEN
Disease-related cells differentiated from patient-derived iPSCs are useful for elucidating the pathophysiological mechanisms underlying these diseases. In this study, four iPSC lines were established from independent patients with sensorineural hearing loss and a mutation in EYA4. These iPSCs showed pluripotency, the capacity to differentiate into three germ layers, and normal karyotypes, suggesting that these lines are useful for the pathological study of sensorineural hearing loss and drug screening for ear disorders.
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Pérdida Auditiva Sensorineural , Células Madre Pluripotentes Inducidas , Mutación , Humanos , Pérdida Auditiva Sensorineural/genética , Pérdida Auditiva Sensorineural/patología , Células Madre Pluripotentes Inducidas/metabolismo , Masculino , Línea Celular , Femenino , Transactivadores/genética , Diferenciación Celular , Niño , CariotipoRESUMEN
Apolipoprotein E (APOE)is the gene with greatest genetic risk for Alzheimer's disease (AD). We successfully established a human induced pluripotent stem cell(iPSC) line from a woman mutated by APOE gene. The cell line was isolated from this woman's peripheral blood mononuclear cells using a non-integrated Sendai virus, which retained the original genotype, showed a normal karyotype, highly expressed pluripotent markers and could differentiate into three germ layers.
Asunto(s)
Apolipoproteínas E , Células Madre Pluripotentes Inducidas , Mutación , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/citología , Femenino , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Línea Celular , Diferenciación Celular , Cariotipo , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/citologíaRESUMEN
Chondrichthyes is an important lineage to reconstruct the evolutionary history of vertebrates. Here, we analyzed genome synteny for six chondrichthyan chromosome-level genomes. Our comparative analysis reveals a slow evolutionary rate of chromosomal changes, with infrequent but independent fusions observed in sharks, skates, and chimaeras. The chondrichthyan common ancestor had a proto-vertebrate-like karyotype, including the presence of 18 microchromosome pairs. The X chromosome is a conversed microchromosome shared by all sharks, suggesting a likely common origin of the sex chromosome at least 181 million years ago. We characterized the Y chromosomes of two sharks that are highly differentiated from the X except for a small young evolutionary stratum and a small pseudoautosomal region. We found that shark sex chromosomes lack global dosage compensation but that dosage-sensitive genes are locally compensated. Our study on shark chromosome evolution enhances our understanding of shark sex chromosomes and vertebrate chromosome evolution.