Showing papers on "Karyotype published in 2009"
TL;DR: Apart from certain minor but well defined chromosome regions with especially strong fluorescence, which are subject to certain individual variations, the fluorescence patterns were shown to be quite stable and reproducible.
Abstract: Certain fluorescent DNA-binding compounds, among them quinacrine mustard and quinacrine, give characteristic banding patterns in human metaphase chromosomes; these patterns can be used to identify all the 24 chromosome types as well as chromosome aberrations. The patterns given by quinacrine mustard are especially clear and stable and are suitable for chromosome identification either visually—preferably after contrast enhancement by photography—or by photometric methods. The typical fluorescence pattern of each chromosome type is described.
The reproducibility and variability of the patterns have been analysed by photometric measurements of the patterns in a material of about 5000 chromosomes from 14 healthy subjects. Apart from certain minor but well defined chromosome regions with especially strong fluorescence, which are subject to certain individual variations, the fluorescence patterns were shown to be quite stable and reproducible.
623 citations
TL;DR: A longitudinal study of the prevalence and dynamics of gross chromosomal rearrangements, including aneuploidy, in the presence and absence of fluconazole during a well-controlled in vitro evolution experiment using Candida albicans.
Abstract: The evolution of drug resistance is an important process that affects clinical outcomes. Resistance to fluconazole, the most widely used antifungal, is often associated with acquired aneuploidy. Here we provide a longitudinal study of the prevalence and dynamics of gross chromosomal rearrangements, including aneuploidy, in the presence and absence of fluconazole during a well-controlled in vitro evolution experiment using Candida albicans, the most prevalent human fungal pathogen. While no aneuploidy was detected in any of the no-drug control populations, in all fluconazole-treated populations analyzed an isochromosome 5L [i(5L)] appeared soon after drug exposure. This isochromosome was associated with increased fitness in the presence of drug and, over time, became fixed in independent populations. In two separate cases, larger supernumerary chromosomes composed of i(5L) attached to an intact chromosome or chromosome fragment formed during exposure to the drug. Other aneuploidies, particularly trisomies of the smaller chromosomes (Chr3–7), appeared throughout the evolution experiment, and the accumulation of multiple aneuploid chromosomes per cell coincided with the highest resistance to fluconazole. Unlike the case in many other organisms, some isolates carrying i(5L) exhibited improved fitness in the presence, as well as in the absence, of fluconazole. The early appearance of aneuploidy is consistent with a model in which C. albicans becomes more permissive of chromosome rearrangements and segregation defects in the presence of fluconazole.
293 citations
TL;DR: In this article, the authors reported the molecular genetic analysis of a PE-2 derived diploid (JAY270) and the complete genome sequence of a haploid derivative (Jay291), which is highly heterozygous (approximately 2 SNPs/kb) and has several structural polymorphisms between homologous chromosomes.
Abstract: Bioethanol is a biofuel produced mainly from the fermentation of carbohydrates derived from agricultural feedstocks by the yeast Saccharomyces cerevisiae. One of the most widely adopted strains is PE-2, a heterothallic diploid naturally adapted to the sugar cane fermentation process used in Brazil. Here we report the molecular genetic analysis of a PE-2 derived diploid (JAY270), and the complete genome sequence of a haploid derivative (JAY291). The JAY270 genome is highly heterozygous (approximately 2 SNPs/kb) and has several structural polymorphisms between homologous chromosomes. These chromosomal rearrangements are confined to the peripheral regions of the chromosomes, with breakpoints within repetitive DNA sequences. Despite its complex karyotype, this diploid, when sporulated, had a high frequency of viable spores. Hybrid diploids formed by outcrossing with the laboratory strain S288c also displayed good spore viability. Thus, the rearrangements that exist near the ends of chromosomes do not impair meiosis, as they do not span regions that contain essential genes. This observation is consistent with a model in which the peripheral regions of chromosomes represent plastic domains of the genome that are free to recombine ectopically and experiment with alternative structures. We also explored features of the JAY270 and JAY291 genomes that help explain their high adaptation to industrial environments, exhibiting desirable phenotypes such as high ethanol and cell mass production and high temperature and oxidative stress tolerance. The genomic manipulation of such strains could enable the creation of a new generation of industrial organisms, ideally suited for use as delivery vehicles for future bioenergy technologies.
251 citations
TL;DR: Overall, the large-scale analyses of karyotype features within a well-supported phylogenetic framework enabled the most likely patterns of chromosome evolution in Liliaceae to be reconstructed, highlighting diverse modes of kARYotype evolution, even within this comparatively small monocot family.
172 citations
TL;DR: The Giemsa bands of the rat karyotype are described and numbered and examples are given of the application of the system to marker chromosomes from induced rat sarcomas.
Abstract: In many types of chromosomal work the need for chromosome banding nomenclature is obvious. A well-developed nomenclature system already exists for human chromosomes and in the present communication an attempt is made to adapt this system to the chromosomes of the laboratory rat. The Giemsa bands of the rat karyotype are described and numbered and examples are given of the application of the system to marker chromosomes from induced rat sarcomas. The use of chromosome banding, especially in relation to cancer chromosomes, is discussed.
156 citations
TL;DR: It is suggested that lizard sex determination may be much more the result of an interplay between sex chromosomes and temperature than previously thought, such that the sex determination mode is influenced by the nature of heterogamety as well as temperature sensitivity and the stage of sex chromosome degeneration.
Abstract: Reptiles epitomize the variability of reproductive and sex determining modes and mechanisms among amniotes. These modes include gonochorism (separate sexes) and parthenogenesis, oviparity, viviparity, and ovoviviparity, genotypic sex determination (GSD) with male (XX/XY) and female (ZZ/ZW) heterogamety and temperature-dependent sex determination (TSD). Lizards (order Squamata, suborder Sauria) are particularly fascinating because the distribution of sex-determining mechanisms shows no clear phylogenetic segregation. This implies that there have been multiple transitions between TSD and GSD, and between XY and ZW sex chromosome systems. Approximately 1,000 species of lizards have been karyotyped and among those, fewer than 200 species have sex chromosomes, yet they display remarkable diversity in morphology and degree of degeneration. The high diversity of sex chromosomes as well as the presence of species with TSD, imply multiple and independent origins of sex chromosomes, and suggest that the mechanisms of sex determination are extremely labile in lizards. In this paper, we review the current state of knowledge of sex chromosomes in lizards and the distribution of sex determining mechanisms and sex chromosome forms within and among families. We establish for the first time an association between the occurrence of female heterogamety and TSD within lizard families, and propose mechanisms by which female heterogamety and TSD may have co-evolved. We suggest that lizard sex determination may be much more the result of an interplay between sex chromosomes and temperature than previously thought, such that the sex determination mode is influenced by the nature of heterogamety as well as temperature sensitivity and the stage of sex chromosome degeneration.
155 citations
TL;DR: The identified genetic aberrations were not confined to MIFS; an identical t(1;10) was also found in a case of HFT and the amplicon in 3p was seen in an IMFH and the consequences of these alterations for gene expression were assessed.
Abstract: Myxoinflammatory fibroblastic sarcoma (MIFS) is a low-grade malignant neoplasm for which limited genetic information, including a t(1;10)(p22;q24) and amplification of chromosome 3 material, is available. To further characterize these aberrations, we have investigated eight soft tissue sarcomas diagnosed as MIFS, haemosiderotic fibrolipomatous tumour (HFT), myxoid spindle cell/pleomorphic sarcoma with MIFS features, and inflammatory malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma with prominent inflammation (IMFH) harbouring a t(1;10) or variants thereof and/or ring chromosomes with possible involvement of chromosome 3. Using chromosome banding, fluorescence in situ hybridization, array-based comparative genomic hybridization, global gene expression, and real-time quantitative PCR analyses, we identified the breakpoint regions on chromosomes 1 and 10, demonstrated and delineated the commonly amplified region on chromosome 3, and assessed the consequences of these alterations for gene expression. The breakpoints in the t(1;10) mapped to TGFBR3 in 1p22 and in or near MGEA5 in 10q24, resulting in transcriptional up-regulation of NPM3 and particularly FGF8, two consecutive genes located close to MGEA5. The ring chromosomes contained a commonly amplified 1.44 Mb region in 3p11-12, which was associated with increased expression of VGLL3 and CHMP2B. The identified genetic aberrations were not confined to MIFS; an identical t(1;10) was also found in a case of HFT and the amplicon in 3p was seen in an IMFH. Copyright (c) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. (Less)
128 citations
TL;DR: Comparison of the Atlantic salmon chromosome map with that of rainbow trout provides strong evidence for conservation of large syntenic blocks in these species, corresponding to entire chromosome arms in the rainbow trout.
Abstract: Most teleost species, especially freshwater groups such as the Esocidae which are the closest relatives of salmonids, have a karyotype comprising 25 pairs of acrocentric chromosomes and 48–52 chromosome arms. After the common ancestor of salmonids underwent a whole genome duplication, its karyotype would have 100 chromosome arms, and this is reflected in the modal range of 96–104 seen in extant salmonids (e.g., rainbow trout). The Atlantic salmon is an exception among the salmonids as it has 72–74 chromosome arms and its karyotype includes 12 pairs of large acrocentric chromosomes, which appear to be the result of tandem fusions. The purpose of this study was to integrate the Atlantic salmon's linkage map and karyotype and to compare the chromosome map with that of rainbow trout. The Atlantic salmon genetic linkage groups were assigned to specific chromosomes in the European subspecies using fluorescence in situ hybridization with BAC probes containing genetic markers mapped to each linkage group. The genetic linkage groups were larger for metacentric chromosomes compared to acrocentric chromosomes of similar size. Comparison of the Atlantic salmon chromosome map with that of rainbow trout provides strong evidence for conservation of large syntenic blocks in these species, corresponding to entire chromosome arms in the rainbow trout. It had been suggested that some of the large acrocentric chromosomes in Atlantic salmon are the result of tandem fusions, and that the small blocks of repetitive DNA in the middle of the arms represent the sites of chromosome fusions. The finding that the chromosomal regions on either side of the blocks of repetitive DNA within the larger acrocentric chromosomes correspond to different rainbow trout chromosome arms provides support for this hypothesis.
127 citations
TL;DR: An improved resolution of the G-band pattern has been achieved in prosome analysis of the (8;14) translocation of Burkitt’s lymphoma and the concept of local prosomisation was introduced and discussed.
Abstract: By means of the ”prosome” analysis technique. by which chromosomes are studied at early metaphase and even at prophase. an improved resolution of the G-band pattern has been achieved. The 2 chromosome regions of especial significance in the (8;14) translocation of Burkitt’s lymphoma, 8q24 and 14q32, which in the Pans karyotype were represented as uniformly negative, in prosome analysis resolved into 5 and 6 subbands respectively. The (8;14) translocation was shown to be reciprocal and the breaking points could be established in both chromosomes with more precision than earlier. It was noticed that the segment of No. 8. translocated onto No. 14, exhibited somewhat different morphologic features in translocated than in normal position. The concept of local prosomisation was introduced and discussed. Yanka Manolova, Oncological Research Institute, Sofia 1156, Bulgaria
117 citations
TL;DR: Results show that PrBn changes the rate of recombination between nonhomologous chromosomes during meiosis of B. napus haploids and also affects homologous recombination with an effect that depends on plant karyotype.
Abstract: Although the genetic regulation of recombination in allopolyploid species plays a pivotal role in evolution and plant breeding, it has received little recent attention, except in wheat (Triticum aestivum). PrBn is the main locus that determines the number of nonhomologous associations during meiosis of microspore cultured Brassica napus haploids (AC; 19 chromosomes). In this study, we examined the role played by PrBn in recombination. We generated two haploid × euploid populations using two B. napus haploids with differing PrBn (and interacting genes) activity. We analyzed molecular marker transmission in these two populations to compare genetic changes, which have arisen during meiosis. We found that cross-over number in these two genotypes was significantly different but that cross-overs between nonhomologous chromosomes showed roughly the same distribution pattern. We then examined genetic recombination along a pair of A chromosomes during meiosis of B. rapa × B. napus AAC and AACC hybrids that were produced with the same two B. napus genotypes. We observed significant genotypic variation in cross-over rates between the two AAC hybrids but no difference between the two AACC hybrids. Overall, our results show that PrBn changes the rate of recombination between nonhomologous chromosomes during meiosis of B. napus haploids and also affects homologous recombination with an effect that depends on plant karyotype.
111 citations
TL;DR: The results suggest that in reptiles the origin of sex chromosomes varies even within such a small clade as the order Squamata, employing a variety of genetic sex determination.
Abstract: Populations of the gecko lizard Gekko hokouensis (Gekkonidae, Squamata) on Okinawajima Island and a few other islands of the Ryukyu Archipelago, Japan, have the morphologically differentiated sex chromosomes, the acrocentric Z chromosome and the subtelocentric W chromosome, although the continental representative of this species reportedly shows no sex chromosome heteromorphism. To investigate the origin of sex chromosomes and the process of sex chromosomal differentiation in this species, we molecularly cloned the homologues of six chicken Z-linked genes and mapped them to the metaphase chromosomes of the Okinawajima sample. They were all localized to the Z and W chromosomes in the order ACO1/IREBP–RPS6–DMRT1–CHD1–GHR–ATP5A1, indicating that the origin of ZW chromosomes in G. hokouensis is the same as that in the class Aves, but is different from that in the suborder Ophidia. These results suggest that in reptiles the origin of sex chromosomes varies even within such a small clade as the order Squamata, employing a variety of genetic sex determination. ACO1/IREBP, RPS6, and DMRT1 were located on the Z long arm and the W short arm in the same order, suggesting that multiple rearrangements have occurred in this region of the W chromosome, where genetic differentiation between the Z and W chromosomes has been probably caused by the cessation of meiotic recombination.
TL;DR: Despite their inclusion in the same major karyotypic group, the distinct populations of Hoplias malabaricus cannot be considered an absolute evolutionary unit, as evidenced by their inner chromosomal differentiations.
Abstract: Karyotype and chromosomal characteristics from 3 allopatric populations of Hoplias malabaricus, cytogenetically the most studied Erythrinidae taxon, were investigated using different staining techniques (C-, Ag-, and CMA(3) banding) as well as fluorescent in situ hybridization (FISH) to detect 18S rDNA, 5S rDNA, and 5SHindIII satellite DNA sites. The isolation, cloning and characterization of an 18S rDNA probe from H. malabaricus genome were also performed for the first time in order to develop a more specific probe. The 3 populations, named PR, CR, and DR, showed identical karyotypes, with 2n = 42 chromosomes composed of 11 m pairs and 10 sm pairs, without heteromorphic sex chromosomes, which characterize the populations as belonging to karyomorph A. In all populations C-positive heterochromatin was situated in the centromeric/pericentromeric regions of the chromosomes, as well as in the telomeric region of several pairs. A conspicuous proximal heterochromatic block on the long arm of pair No. 16 was the only GC-rich segment in the karyotypes. 5SHindIII satellite DNA was always mapped in the centromeric region of several chromosomes. The 18S rDNA sites were situated on the telomeric or centromeric regions, whereas the 5S rDNA showed an interstitial or proximal location in some pairs. Several chromosomes bearing these repetitive DNA sequences were shared by the 3 populations, alongside with some exclusive chromosomal markers. In this sense, population CR was the most differentiated one, including a syntenic condition for the 18S and 5S rDNA probes, as confirmed by double FISH. Thus, despite their inclusion in the same major karyotypic group, the distinct populations cannot be considered an absolute evolutionary unit, as evidenced by their inner chromosomal differentiations.
TL;DR: Findings indicate that the C-bands are aggregated in the cell and/or that such an aggregation is induced by mitomycin C.
Abstract: Mitomycin C induced chromosome aberrations were analysed in cultured human lymphocytes by the quinacrine mustard chromosome banding technique. There was an overrepresentation of interchange aberrations involving the C-bands of homologous chromosomes, and especially the secondary constrictions of chromosomes 1, 9 and 16. Interchanges involving other bands rarely occurred between homologous chromosomes. These findings indicate that the C-bands are aggregated in the cell and/or that such an aggregation is induced by mitomycin C. The chromatid and chromosome breaks appeared to be located preferentially in the R-bands.
TL;DR: In the eight statistically significant CNVs found, the first study of CNV analysis in a large cohort of Caucasian POF patients is reported, it found five genes involved in reproduction, thus representing potential candidate genes in POF.
Abstract: Introduction: Premature ovarian failure (POF) is defined by amenorrhea of at least 4- to 6-month duration, occurring before 40 yr of age, with two FSH levels in the postmenopausal range. Its etiology remains unknown in more than 80% of cases. Standard karyotypes, having a resolution of 5–10 Mb, have identified critical chromosomal regions, mainly located on the long arm of the X chromosome. Array comparative genomic hybridization (a-CGH) analysis is able to detect submicroscopic chromosomal rearrangements with a higher genomic resolution. We searched for copy number variations (CNVs), using a-CGH analysis with a resolution of approximately 0.7 Mb, in a cohort of patients with POF. Patients and Methods: We prospectively included 99 women. Our study included a conventional karyotype and DNA microarrays comprising 4500 bacterial artificial chromosome clones spread on the entire genome. Results: Thirty-one CNVs have been observed, three on the X chromosome and 28 on autosomal chromosomes. Data have been compa...
TL;DR: Both centromere activation and inactivation in cucurbit species were associated with a gain/loss of a large amount of pericentromeric heterochromatin.
Abstract: The centromere of an eukaryotic chromosome can move to a new position during evolution, which may result in a major alteration of the chromosome morphology and karyotype. This centromere repositioning phenomenon has been extensively documented in mammalian species and was implicated to play an important role in mammalian genome evolution. Here we report a centromere repositioning event in plant species. Comparative fluorescence in situ hybridization mapping using common sets of fosmid clones between two pairs of cucumber (Cucumis sativus L.) and melon (Cucumis melo L.) chromosomes revealed changes in centromere positions during evolution. Pachytene chromosome analysis revealed that the current centromeres of all four cucumber and melon chromosomes are associated with distinct pericentromeric heterochromatin. Interestingly, inactivation of a centromere in the original centromeric region was associated with a loss or erosion of its affixed pericentromeric heterochromatin. Thus, both centromere activation and inactivation in cucurbit species were associated with a gain/loss of a large amount of pericentromeric heterochromatin.
TL;DR: Candida albicans strains are particularly prone to undergo changes in chromosome number during the stresses of DNA transformation protocols, and the hypothesis that stresses conferred by heat and/or LiOAc exposure promote chromosome number changes during DNA transformation procedures is tested.
Abstract: Candida albicans strains tolerate aneuploidy, historically detected as karyotype alterations by pulsed-field gel electrophoresis and more recently revealed by array comparative genome hybridization, which provides a comprehensive and detailed description of gene copy number. Here, we first retrospectively analyzed 411 expression array experiments to predict the frequency of aneuploidy in different strains. As expected, significant levels of aneuploidy were seen in strains exposed to stress conditions, including UV light and/or sorbose treatment, as well as in strains that are resistant to antifungal drugs. More surprisingly, strains that underwent transformation with DNA displayed the highest frequency of chromosome copy number changes, with strains that were initially aneuploid exhibiting 3-fold more copy number changes than strains that were initially diploid. We then prospectively analyzed the effect of lithium acetate (LiOAc) transformation protocols on the stability of trisomic chromosomes. Consistent with the retrospective analysis, the proportion of karyotype changes was highly elevated in strains carrying aneuploid chromosomes. We then tested the hypothesis that stresses conferred by heat and/or LiOAc exposure promote chromosome number changes during DNA transformation procedures. Indeed, a short pulse of very high temperature caused frequent gains and losses of multiple chromosomes or chromosome segments. Furthermore, milder heat exposure over longer periods caused increased levels of loss of heterozygosity. Nonetheless, aneuploid chromosomes were also unstable when strains were transformed by electroporation, which does not include a heat shock step. Thus, aneuploid strains are particularly prone to undergo changes in chromosome number during the stresses of DNA transformation protocols.
TL;DR: Identification of the individual chromosomes in the rye variety “Stalrag” and in two inbred lines of rye was carried out by means of the Giemsa C-banding technique and related to earlier investigations.
Abstract: Identification of the individual chromosomes in the rye variety “Stalrag” and in two inbred lines of rye was carried out by means of the Giemsa C-banding technique and related to earlier investigations. Heterochromatin polymorphism occurs between plants and between homologues. Possible explanations of the variability of the banding pattern are discussed. Grouping of heterochromatic regions at interphase and fused telomeres at prophase were observed and discussed.
TL;DR: In this paper, a 3-kb genomic sequence was used to mark the Z and W microchromosomes of the Australian central bearded dragon (Pogona vitticeps) to chromosomes of 12 species of Australian agamids from eight genera using fluorescence in-situ hybridization.
Abstract: Distribution of sex-determining mechanisms across Australian agamids shows no clear phylogenetic segregation, suggesting multiple transitions between temperature-dependent (TSD) and genotypic sex determination (GSD). These taxa thus present an excellent opportunity for studying the evolution of sex chromosomes, and evolutionary transitions between TSD and GSD. Here we report the hybridization of a 3 kb genomic sequence (PvZW3) that marks the Z and W microchromosomes of the Australian central bearded dragon (Pogona vitticeps) to chromosomes of 12 species of Australian agamids from eight genera using fluorescence in-situ hybridization (FISH). The probe hybridized to a single microchromosome pair in 11 of these species, but to the tip of the long arm of chromosome pair 2 in the twelfth (Physignathus lesueurii), indicating a micro-macro chromosome rearrangement. Three TSD species shared the marked microchromosome, implying that it is a conserved autosome in related species that determine sex by temperature. C-banding identified the marked microchromosome as the heterochromatic W chromosome in two of the three GSD species. However, in Ctenophorus fordi, the probe hybridized to a different microchromosome from that shown by C-banding to be the heterochromatic W, suggesting an independent origin for the ZW chromosome pair in that species. Given the haphazard distribution of GSD and TSD in this group and the existence of at least two sets of sex microchromosomes in GSD species, we conclude that sex-determining mechanisms in this family have evolved independently, multiple times in a short evolutionary period.
TL;DR: The risk of developing any kind of gonadal lesion, whether tumoral or not, justifies investigation of Y-chromosome sequences by means of the polymerase chain reaction (PCR), a highly sensitive, low-cost and easy-to-perform technique.
Abstract: Turner syndrome (TS) is one of the most common types of aneuploidy among humans, and is present in 1:2000 newborns with female phenotype. Cytogenetically, the syndrome is characterized by sex chromosome monosomy (45,X), which is present in 50-60% of the cases. The other cases present mosaicism, with a 45,X cell line accompanied by one or more other cell lines with a complete or structurally abnormal X or Y chromosome. The presence of Y-chromosome material in patients with dysgenetic gonads increases the risk of gonadal tumors, especially gonadoblastoma. The greatest concern is the high risk of developing gonadoblastoma or other tumors and virilization during puberty if chromosome Y-specific sequences are present. The role of the Y chromosome in human oncogenesis is still controversial. Even though gonadoblastoma is a benign tumor, it can undergo transformation into invasive dysgerminoma in 60% of the cases, and also into other, malignant forms of germ cell tumors. Although some authors have questioned the high incidence of gonadoblastoma (around 30%), the risk of developing any kind of gonadal lesion, whether tumoral or not, justifies investigation of Y-chromosome sequences by means of the polymerase chain reaction (PCR), a highly sensitive, low-cost and easy-to-perform technique. In conclusion, mosaicism of both the X and the Y chromosome is a common finding in TS, and detection of Y-chromosome-specific sequences in patients, regardless of their karyotype, is necessary in order to prevent the development of gonadal lesions.
TL;DR: The chromosome pattern was studied by conventional and Giemsa banding techniques in 5 polyps from one patient with polyposis coli and in sporadic adenomas from 4 patients, suggesting a similar chromosomal evolution in colonicAdenomas regardless of whether they have a hereditary basis or not.
Abstract: The chromosome pattern was studied by conventional and Giemsa banding techniques in 5 polyps from one patient with polyposis coli and in sporadic adenomas from 4 patients In both the familial and the non-familial types chromosomal changes preceded histologic signs of invasiveness In both types preferential engagement of chromosomes Nos 8 and 14 was found, suggesting a similar chromosomal evolution in colonic adenomas regardless of whether they have a hereditary basis or not The rate of progression, however, was faster in the familia type of colonic polyps, which may reflect the more malignant potential of these tumors
TL;DR: At least one half of cases of normal karyotype acute myeloid leukemia/myelodysplastic syndrome have readily identifiable genomic abnormalities, as found by the analysis; the high frequency of copy-number neutral loss of heterozygosity is especially notable.
Abstract: Background Acute myeloid leukemia is a clonal hematopoietic malignant disease; about 45–50% of cases do not have detectable chromosomal abnormalities. Here, we identified hidden genomic alterations and novel disease-related regions in normal karyotype acute myeloid leukemia/myelodysplastic syndrome samples.Design and Methods Thirty-eight normal karyotype acute myeloid leukemia/myelodysplastic syndrome samples were analyzed with high-density single-nucleotide polymorphism microarray using a new algorithm: allele-specific copy-number analysis using anonymous references (AsCNAR). Expression of mRNA in these samples was determined by mRNA microarray analysis.Results Eighteen samples (49%) showed either one or more genomic abnormalities including duplication, deletion and copy-number neutral loss of heterozygosity. Importantly, 12 patients (32%) had copy-number neutral loss of heterozygosity, causing duplication of either mutant FLT3 (2 cases), JAK2 (1 case) or AML1/RUNX1 (1 case); and each had loss of the normal allele. Nine patients (24%) had small copy-number changes (< 10 Mb) including deletions of NF1, ETV6/TEL, CDKN2A and CDKN2B. Interestingly, mRNA microarray analysis showed a relationship between chromosomal changes and mRNA expression levels: loss or gain of chromosomes led, respectively, to either a decrease or increase of mRNA expression of genes in the region.Conclusions This study suggests that at least one half of cases of normal karyotype acute myeloid leukemia/myelodysplastic syndrome have readily identifiable genomic abnormalities, as found by our analysis; the high frequency of copy-number neutral loss of heterozygosity is especially notable.
TL;DR: The correlations between size, taxonomic diversity and rates of karyotype evolution are discussed in the light of results from theoretical models describing the spread of chromosome mutations in populations and particular attention is given to the role reproductive biology may play in influencing the rate of kARYotype evolution.
Abstract: The genera of eutherian mammals have been divided into two groups depending on whether the animals in the genera have high or low rates of karyotype evolution. The rate of karyotype evolution in a genus is estimated by the standard deviation of the chromosome numbers within the genus. The estimates have been found to correlate with the size of the animals and the taxonomic diversity of the genera: small animals have a higher rate of karyotype evolution than large animals, and animals belonging to genera with many taxa have a higher rate of karyotype evolution than animals belonging to genera with few taxa. No correlation has been found between the chromosome number and the rate of karyotype evolution. The analyses are made by comparing genera which belong to the same taxonomic family. Our results are consistent with the results obtained by A. C. Wilson, G. Bush and their co-workers using different methods of estimation and comparison.
The correlations between size, taxonomic diversity and rates of karyotype evolution are discussed in the light of results from theoretical models describing the spread of chromosome mutations in populations. Particular attention is given to the role reproductive biology may play in influencing the rate of karyotype evolution.
TL;DR: An overview of the biology of mammalian sex development as a scientific background for better understanding the body of knowledge of the clinical cytogenetics of disorders of sex development in domestic animals is presented.
Abstract: The association of abnormal chromosome constitutions and disorders of sex development in domestic animals has been recorded since the beginnings of conventional cytogenetic analysis. Deviated karyotypes consisting of abnormal sex chromosome sets (e.g. aneuploidy) and/or the coexistence of cells with different sex chromosome constitutions (e.g. mosaicism or chimerism) in an individual seem to be the main causes of anomalies of sex determination and sex differentiation. Molecular cytogenetics and genetics have increased our understanding of these pathologies, where human and mouse models have provided a substantial amount of knowledge, leading to the discovery of a number of genes implicated in mammalian sex determination and differentiation. Additionally, other genes, which appeared to be involved in ovary differentiation, have been found by investigations in domestic species such as the goat. In this paper, we present an overview of the biology of mammalian sex development as a scientific background for better understanding the body of knowledge of the clinical cytogenetics of disorders of sex development in domestic animals. An attempt to summarize of what has been described in that particular subject of veterinary medicine for each of the main mammalian domestic species is presented here.
TL;DR: The association of isochromosome number 17 with blast crisis was confirmed and new data were obtained concerning the significance of duplicated or dicentric Ph1 chromosomes and their relationship with the 9q+ anomaly.
Abstract: A cytogenetic study of Ph1 positive myeloid leukaemia in both chronic and acute phases had been made by a chromosome banding technique. The translocation (t(9;22)(q34;q11), designated t(Ph1) was present in the myeloid cells of 43 of 44 patients; the exceptional case had normal number 9 chromosomes and a different translocation (t(19;22)(q13;q11)). A translocation additional to that involving the Ph1 was found as a stable abnormality present in all myeloid cells in 4 patients, chromosome 17 being involved in 2. The association of isochromosome number 17 with blast crisis was confirmed. New data were obtained concerning the significance of duplicated or dicentric Ph1 chromosomes and their relationship with the 9q+ anomaly. Monoclonal origin of Ph1 was confirmed in cases with polymorphic number 22 or 9 chromosomes.
TL;DR: Quantitative PCR confirmed that GDX XX mice have higher Pdyn expression in striatum than XY mice, regardless of their gonadal sex, indicating that the sex chromosome effect is the result of XX vs. XY differences in the number of X chromosomes.
Abstract: Previous research suggests that sex differences in the nigrostriatal system are created by direct effects of the sex chromosomes (XX vs. XY), independent of the action of gonadal hormones. Here we tested for sex chromosome effects on expression of three mRNAs in the striatum and nucleus accumbens of adult mice of the four core genotypes model (XX and XY gonadal males, XX and XY gonadal females). Mice were gonadectomized (GDX) at 47-51 days old to eliminate group differences in the levels of gonadal steroids. Three weeks later, mice were killed and brains collected for in situ hybridization of the striatum, or the striatum was dissected out for quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Expression in XX and XY mice was measured by in situ hybridization using riboprobes encoding the dynorphin precursor Pdyn (prodynorphin), the substance P precursor Tac1 (preprotachykinin) or dopamine D2 receptor. XX mice had higher expression, relative to XY mice of the same gonadal sex, of Pdyn and Tac1 mRNA in specific striatal regions. Quantitative PCR confirmed that GDX XX mice have higher Pdyn expression in striatum than XY mice, regardless of their gonadal sex. XX had higher Pdyn expression than XY or XO mice, indicating that the sex chromosome effect is the result of XX vs. XY differences in the number of X chromosomes, probably because of sex differences in the expression of X gene(s) that escape inactivation. We detected no sex chromosome effect on D2 receptor mRNA.
TL;DR: It is concluded that MYC dysregulation by complex mechanisms is one of the major molecular events in the oncogenesis of PCL.
Abstract: Plasma cell leukemia (PCL) is a rare form of monoclonal gammopathy, which can originate de novo or evolve from multiple myeloma (MM) as a terminal leukemic phase. Previous cytogenetic studies of PCL have reported the presence of complex karyotypes with involvement of multiple unidentified chromosomal regions. We report here the analysis of 12 PCL (10 primary and two secondary) by metaphase and FISH analysis combined with oligonucleotide array data (244 k, Agilent). Interphase-FISH results were compared with those from a series of 861 newly diagnosed patients with MM. Cytogenetic analysis was successful on 11 patients, all of whom showed clonal chromosomal abnormalities. Compared with MM, t(11;14)(q13;q32) (42% versus 15%; P = 0.027) and t(14;16)(q32;q23) (25% versus 4%; P = 0.010) were more frequent in PCL, although neither the specific partner chromosome involved in the IgH translocation nor the ploidy status predicted for survival. Chromosomes 1, 8, 13, and 16 showed the highest number of copy number alterations with 8q24 being the chromosomal region most frequently involved. In eight of 12 patients we found abnormalities (translocations, one amplification, small deletions, and duplications) that directly targeted or were very close to MYC. Only four of these changes were detected by routine FISH analysis using commercial probes with the others exclusively detected by arrays. Quantitative reverse transcription polymerase chain reaction demonstrated that these different abnormalities were associated with increased levels of MYC mRNA. We conclude that MYC dysregulation by complex mechanisms is one of the major molecular events in the oncogenesis of PCL
TL;DR: Chromosome location of H3-H4 histone gene clusters seem to be highly conservative in Acrididae grasshoppers, which is most parsimoniously explained by common ancestry.
Abstract: We analyse chromosome location of H3 and H4 histone gene clusters by fluorescence in-situ hybridization (FISH) in 35 species of Acrididae grasshoppers belonging to seven subfamilies. As in other organisms, H3 and H4 co-localized in the same chromosome region in the 11 species where double FISH was performed with the H3 and H4 DNA probes. Chromosome location of H3-H4 histone gene clusters showed high regularity in the species analysed, with all of them carrying a single H3-H4 cluster in an autosome which, in most cases, was located interstitially in the proximal chromosome third. In 17 out of the 21 species with 2n♂ = 23 acrocentric chromosomes, the H3-H4-carrying autosome was about eighth in order of decreasing size. Two of the four exceptions changed H3-H4 localization to proximal (Pezotettix giornae) or distal (Tropidopola graeca) in the eighth-sized autosome, but the remainder (the two Eyprepocnemis species) showed the H3-H4 cluster distally located in the second-sized autosome. All 14 species with 2n♂ = 17 chromosomes (including three long metacentric autosome pairs, five acrocentric autosome pairs and an acrocentric X chromosome) carried an interstitial H3-H4 cluster in the short arm of the smallest of the three long metacentric pairs. These results suggest that chromosome location of H3-H4 histone gene clusters seem to be highly conservative in Acrididae grasshoppers. The change in H3-H4 location from the acrocentric medium-sized autosome in the 2n♂ = 23 karyotype to the long metacentric autosome in the 2n♂ = 17 karyotype is most parsimoniously explained by common ancestry, i.e. by the involvement of the H3-H4-carrying acrocentric in the centric fusion that gave rise to the smallest of the three long metacentric autosomes of 2n♂ = 17 species.
TL;DR: A comprehensive approach using cytogenetic karyotyping, polymerase chain reaction (PCR)‐based genotypes, and microarray‐based comparative genomic hybridization (arrayCGH) in combination to analyze chromosomal profiles of 115 first‐trimester miscarriages of Chinese women is employed.
Abstract: Miscarriage is the spontaneous loss of an embryo or fetus before the 20th week of pregnancy. Most miscarriages occur before the end of the first trimester (<13 weeks). Although many risk factors relate to this occurrence, genetic factors play the most important role. Chromosomal abnormalities, including both numerical and structural anomalies, underlie the majority of miscarriages. In this study, we employed a comprehensive approach using cytogenetic karyotyping, polymerase chain reaction (PCR)-based genotyping, and microarray-based comparative genomic hybridization (arrayCGH) in combination to analyze chromosomal profiles of 115 first-trimester miscarriages of Chinese women. Seventy cases (61%) were found to have chromosomal anomalies, of which 90% were numerical and 10% were structural. Cytogenetic karyotyping identified 78.6% (55/70), PCR assays 2.9% (2 triploids), and arrayCGH 18.6% (13/70) of the anomalies. In this study, a microdeletion of 108 kb and four microduplications sizing from 300 to 1460 kb were observed. An advantage of using this combination approach is that microsatellite genotyping and arrayCGH can be accomplished in spite of culture failure and maternal cell contamination. In addition, arrayCGH can detect submicroscopic chromosomal anomalies and gene dosage alterations.
TL;DR: The morphological and banding homologies between the otariid and 34 chromosome phocid karyotypes confirm the theory of monophyletic origin of the Pinnipedia.
Abstract: Cells in short-term culture from 12 species of pinnipeds were submitted to chromosome analysis, including, in 11 of them, chromosome measurements and establishment of idiograms. Analysis of variance was carried out on the measurements of 9 phocids. Comparisons between the different karyotypes were made on the basis of conventional chromosome methods as well as autoradiography, G- and C-band techniques. The Pinnipedia are characterized by a pronounced karyotype uniformity. Within the Otarioidea, all otariids so far studied have 2n = 36 and closely agreeing karyotypes, the walrus has 2n = 32. In the Phocidae 2 chromosome numbers occur, 2n = 34 and 2n = 32. The 2n = 32 karyotype has evolved from the primordial 2n = 34 karyotype through fusion of two pairs. Within each of these two groups all karyotypes are virtually identical. The morphological and banding homologies between the otariid and 34 chromosome phocid karyotypes confirm the theory of monophyletic origin of the Pinnipedia.
TL;DR: The fact that chromosome abnormalities predominantly result in copy number changes rather than specific chromosome or gene fusions suggests that this may be the major mechanism leading to carcinogenesis in colorectal cancer.
Abstract: In defining the genetic profiles in cancer, cytogenetically aberrant cell lines derived from primary tumors are important tools for the study of carcinogenesis. Here, we present the results of a comprehensive investigation of 15 established colorectal cancer cell lines using spectral karyotyping (SKY), fluorescence in situ hybridization, and comparative genomic hybridization (CGH). Detailed karyotypic analysis by SKY on five of the lines (P53HCT116, T84, NCI-H508, NCI-H716, and SK-CO-1) is described here for the first time. The five lines with karyotypes in the diploid range and that are characterized by defects in DNA mismatch repair had a mean of 4.8 chromosomal abnormalities per line, whereas the 10 aneuploid lines exhibited complex karyotypes and a mean of 30 chromosomal abnormalities. Of the 150 clonal translocations, only eight were balanced and none were recurrent among the lines. We also reviewed the karyotypes of 345 cases of adenocarcinoma of the large intestine listed in the Mitelman Database of Chromosome Aberrations in Cancer. The types of abnormalities observed in the cell lines reflected those seen in primary tumors: there were no recurrent translocations in either tumors or cell lines; isochromosomes were the most common recurrent abnormalities; and breakpoints occurred most frequently at the centromeric/pericentromeric and telomere regions. Of the genomic imbalances detected by array CGH, 87% correlated with chromosome aberrations observed in the SKY studies. The fact that chromosome abnormalities predominantly result in copy number changes rather than specific chromosome or gene fusions suggests that this may be the major mechanism leading to carcinogenesis in colorectal cancer.