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Showing papers on "Karyotype published in 2008"


Journal ArticleDOI
TL;DR: Data from a chromosome examination of 14,069 consecutive newborn infants is presented, finding 294 babies with a major chromosome abnormality or distinctive marker chromosomes.
Abstract: Data from a chromosome examination of 14,069 consecutive newborn infants is presented. Successful karyotypes were obtained on 13,939 babies using short-term blood cultures and conventional staining methods. Of those, 13,645 babies had normal chromosomes; 64 (0.46%) had a major chromosome abnormality; and 230 (1.65%) had a marker chromosome; giving a total of 294 (2.11%) babies with a major chromosome abnormality or distinctive marker chromosomes. Six male babies with sex chromosome abnormalities had a 47,XXY and four a 47,XYY karyotype, and three were mixoploids. Five female babies had a 47,XXX karytotype and two were mixoploids. There were three babies with ambiguous external genitalia, all with normal karyotypes. Fourteen babies had 21-trisomy; there were three 18-trisomics and one 13-trisomic. The mother of one 18-trisomy baby had a balanced (18;21) translocation. Twenty-four infants had a balanced chromosome rearrangement. Eleven of these were reciprocal and thirteen were Robertsonian translocations. One baby had an unbalanced derivative chromosome resulting from an 18;11 insertion. Two infants with additional unidentified fragments were detected. Two hundred and thirty babies (1:60) carying distinctive chromosome variants were detected. The commonest variant was the Yq+ among males (0.89%). Other common variants involved the short arms of the D and G groups (0.32% and 0.57%, respectively) 16q+ (0.09%), and 1q+ (0.04%). The results of the present study when combined with five other comparable studies, thus comprising a total of 46,150 newborn infants, indicates that the frequency of major chromosome abnormalities is between 1:150 and 1:200 live-born babies. This represents a small proportion of all conceptuses with chromosome abnormalities, which has been estimated as being approximately 1:20. It is thus clear that chromosome abnormalities form a major part of the genetic load carried by the human population. The development of chromosome banding techniques already has increased, and with further increase, the complexities of human cytogenetics and may reveal many additional rearrangements undetectable by conventional methods.

508 citations


Journal ArticleDOI
TL;DR: In other amniotes (reptiles and birds), sex is determined by a variety of different mechanisms that belong in two broad classes: genetic or environmental, although recent data show that some species combine both (Quinn et al. 2007) as mentioned in this paper.
Abstract: In mammals, with a few notable exceptions, sex is determined by an XX female:XY male sex chromosome system in which the Y chromosome bears the male-dominant testis-determining gene SRY. The X chromosome of most placental mammals has a virtually identical gene content, whereas the degenerate Y chromosome contains overlapping subsets of only a few active genes (for review, see Graves 2006). Marsupial mammals have a smaller X and Y that represent an ancestral therian mammal sex pair and define the ancient region of the human sex chromosomes. The mammal X and Y evolved from a pair of autosomes after the proto-Y acquired a male-determining gene, X–Y recombination between male-advantage genes was suppressed, and the Y degenerated (Charlesworth et al. 2005; Fraser and Heitman 2005; Graves 2006). Mapping orthologs of mammal X-borne genes in other vertebrates will help our understanding of how the mammal XY and the sex-determining (SRY) gene evolved, and also how they function. In other amniotes (reptiles and birds), sex is determined by a variety of different mechanisms that belong in two broad classes: genetic or environmental, although recent data show that some species combine both (Quinn et al. 2007). Genetic sex determination is the most widespread within lineages and commonly involves a pair of differentiated sex chromosomes (for review, see Ezaz et al. 2006). Sex chromosomes are named XY when the heterogametic sex is the male (female XX and male XY as in mammals) and ZW when heterogametic sex is the female (female ZW and male ZZ as in birds or snakes). Amniote XY and ZW sex chromosome pairs are superficially similar. The paired chromosome (X or Z) in the homogametic sex is generally well conserved, large, and gene-rich, whereas the sex-specific Y or W is usually small, heterochromatic, and almost devoid of active genes. However, comparative gene mapping shows that the sex chromosomes of mammals (XY), birds (ZW), and snakes (ZW) are entirely nonhomologous, implying that they evolved from different pairs of autosomes (Fridolfsson et al. 1998; Nanda et al. 2000; Graves and Shetty 2001; Kohn et al. 2004; Matsubara et al. 2006). The sex-determining gene that initiates testis development is also different; for instance, there is no SRY in non-mammal vertebrates, and sex determination in birds seems to be largely controlled by dosage of a Z-borne gene (possibly DMRT1) (Raymond et al. 1999) rather than a male-dominant gene. The similarities shared by sex chromosomes are thus the results of convergent evolutionary forces in different vertebrate lineages. The acquisition of a sex-determining gene on one member of an autosome pair and the accumulation of sex-specific alleles nearby were followed by suppression of recombination between the new proto-sex chromosomes, which resulted in vulnerability to mutation and deletions of the sex-specific chromosome (Y or W) and, therefore, its degradation (Charlesworth and Charlesworth 2000; Charlesworth et al. 2005; Fraser and Heitman 2005; Steinemann and Steinemann 2005; Graves 2006). The original autosome from which the mammal X and Y diverged can be deduced from the relationship of the X pair to other vertebrate sex chromosome systems. The short arm of chromosome 4 in the chicken (Gallus gallus [GGA]) and several autosomal regions in fish share genes with the mammal X, and thus represent this ancestral autosome. How this genomic region took over a sex-determining function from an ancestral temperature-determining system, or from nonhomologous ancestral sex chromosomes, demands exploration of the sex-determining system of the most basal mammal group, the monotremes. Monotremes diverged ∼165 million years ago (Mya) from therian mammals (placentals and marsupials) and therefore fall in the phylogenetic tree between birds/reptiles and therians (Van Rheede et al. 2006; Bininda-Emonds et al. 2007). Monotremes, represented only by the duck-billed platypus Ornithorhynchus anatinus and the echidnas (four species), display a fascinating mixture of mammalian and avian/reptilian morphological, physiological, and karyological features and have a unique reproductive system that combines egg-laying with lactation (for review, see Grutzner and Graves 2004). Monotremes have long been known to possess a complex male heterogametic system in which multiple X and Y chromosomes form a chain at male meiosis (Bick and Sharman 1975; Murtagh 1977; Wrigley and Graves 1988). Recently, individual X and Y chromosomes were identified by chromosome painting (Rens et al. 2004). The male was discovered to have 10 unpaired chromosomes that included five male-specific Y chromosomes and five X chromosomes; the female possesses two copies of the five Xs. In male meiosis, the 10 sex chromosomes form an alternating XY chain, X1Y1X2Y2X3Y3X4Y4X5Y5 (Grutzner et al. 2004), unique in vertebrates (for review, see Grutzner et al. 2006). These 10 chromosomes pair and recombine in pseudoautosomal regions at the termini of adjacent X and Y chromosomes. Little is known about the gene content of the 10 platypus sex chromosomes, but the few available data are extremely striking. Early comparative mapping using radioactive in situ hybridization with heterologous probes suggested that X1, located at one end of the chain, shared homology with the ancient part of the mammalian X (Watson et al. 1990; Wilcox et al. 1996; Mitchell et al. 1998; but see also Waters et al. 2005). At the other end of the chain, fluorescent in situ hybridization (FISH) of a large insert BAC-clone showed that X5 contained the Z-borne putative bird sex-determination gene DMRT1 (Grutzner et al. 2004; El-Mogharbel et al. 2007). This suggested that the monotreme meiotic chain has homology with the therian XY system at one end and to the bird ZW system at the other, and represents an evolutionary link between two systems that were previously thought to have evolved independently (Grutzner et al. 2004; Ezaz et al. 2006). The identity of the platypus sex-determining gene remains mysterious. Many efforts to identify a platypus homolog of the therian testis-determining gene SRY proved fruitless (Grutzner et al. 2004). Progress in platypus genome sequencing and the availability of BAC clones whose gene content can be identified from the database now allow us to partially characterize the gene content of X specific regions and identify genes on the pairing regions between adjacent X and Y chromosomes. We have also tested the hypotheses that platypus sex chromosomes share homology with both the mammal XY and the bird ZW systems. In complete contradiction to early data, we find that the 10 sex chromosomes of platypus share no homology with the ancestral therian X chromosome, which is homologous to platypus chromosome 6. Instead, we find that regions homologous to the chicken Z are scattered throughout the chain, principally on X5 and X3. These results have major implications for our understanding of mammalian sex chromosome evolution.

305 citations


Journal ArticleDOI
TL;DR: It is found that the cells accumulate other recurrent chromosomal abnormalities, including amplification at 20q11.21 and a derivative chromosome 18, which have a variable impact at the transcriptional level.
Abstract: Cultured human embryonic stem (hES) cells have a known predisposition to aneuploidy of chromosomes 12, 17 and X. We studied 17 hES cell lines by array-based comparative genomic hybridization (aCGH) and found that the cells accumulate other recurrent chromosomal abnormalities, including amplification at 20q11.21 and a derivative chromosome 18. These genomic changes have a variable impact at the transcriptional level.

246 citations


Journal ArticleDOI
TL;DR: Comparative chromosome painting is applied to reconstruct karyotype evolution in eight species with x=7 (2n=14, 28) chromosomes from six Brassicaceae tribes to propose that both karyotypes descended from a common ancestor.
Abstract: Karyotype evolution in species with identical chromosome number but belonging to distinct phylogenetic clades is a long-standing question of plant biology, intractable by conventional cytogenetic techniques. Here, we apply comparative chromosome painting (CCP) to reconstruct karyotype evolution in eight species with x=7 (2n=14, 28) chromosomes from six Brassicaceae tribes. CCP data allowed us to reconstruct an ancestral Proto-Calepineae Karyotype (PCK; n=7) shared by all x=7 species analyzed. The PCK has been preserved in the tribes Calepineae, Conringieae, and Noccaeeae, whereas karyotypes of Eutremeae, Isatideae, and Sisymbrieae are characterized by an additional translocation. The inferred chromosomal phylogeny provided compelling evidence for a monophyletic origin of the x=7 tribes. Moreover, chromosomal data along with previously published gene phylogenies strongly suggest the PCK to represent an ancestral karyotype of the tribe Brassiceae prior to its tribe-specific whole-genome triplication. As the PCK shares five chromosomes and conserved associations of genomic blocks with the putative Ancestral Crucifer Karyotype (n=8) of crucifer Lineage I, we propose that both karyotypes descended from a common ancestor. A tentative origin of the PCK via chromosome number reduction from n=8 to n=7 is outlined. Comparative chromosome maps of two important model species, Noccaea caerulescens and Thellungiella halophila, and complete karyotypes of two purported autotetraploid Calepineae species (2n=4x=28) were reconstructed by CCP.

215 citations


Journal ArticleDOI
22 Aug 2008-Science
TL;DR: It is shown that in the fission yeast Schizosaccharomyces pombe, the conditional deletion of the centromere produces survivors that carry either a neocentromere-acquired chromosome at the subtelomeric region or an acentric chromosome rescued by intertelomere fusion with either of the remaining chromosomes.
Abstract: The centromere is essential for the inheritance of genetic information on eukaryotic chromosomes. Epigenetic regulation of centromere identity has been implicated in genome stability, karyotype evolution, and speciation. However, little is known regarding the manner in which centromere dysfunction affects the chromosomal architectures. Here we show that in the fission yeast Schizosaccharomyces pombe, the conditional deletion of the centromere produces survivors that carry either a neocentromere-acquired chromosome at the subtelomeric region or an acentric chromosome rescued by intertelomere fusion with either of the remaining chromosomes. The ratio of neocentromere formation to telomere fusion is considerably decreased by the inactivation of genes involved in RNA interference-dependent heterochromatin formation. By affecting the modes of chromosomal reorganization, the genomic distribution of heterochromatin may influence the fate of karyotype evolution.

189 citations


Journal ArticleDOI
TL;DR: It is hoped that better understanding of genomic alterations will result in identification of novel therapeutic targets and improved prognosis in patients with complex karyotypes.

160 citations


Journal ArticleDOI
TL;DR: The results indicate that clonal chromosomal aberrations may arise transiently in early passage adipose stem cells (ASC) cultures, Nonetheless, incidence of these aberration seems to be negligible in the majority of long‐term ASC cultures, at least under the culture conditions used here.
Abstract: The potential use of human mesenchymal stem cells for therapeutic applications implies large scale in vitro culture, increasing the probability of genetic instability and transformation. We examine here the incidence of unbalanced and balanced chromosome rearrangements in polyclonal and single cell-derived cultures of human adipose stem cells to senescence. G-banding karyotyping of the polyclonal cultures shows a normal karyotype. In addition, high-resolution microarray-based comparative genomic hybridization analyses relative to uncultured adipose stem cells from the same donors reveal overall genomic stability in long-term (∼6 months) polyclonal and clonal culture. One adipose stem cell clone displayed minor deletions in gene-rich telomeric and sub-telomeric regions on three chromosomes in early passage. This however, was detected only in a sub-population of cells that was subsequently spontaneously eliminated from the culture. Apparent pericentromeric instabilities are also occasionally detected in specific chromosomes. Our results indicate that clonal chromosomal aberrations may arise transiently in early passage adipose stem cells (ASC) cultures. Nonetheless, incidence of these aberrations seems to be negligible in the majority of long-term ASC cultures, at least under the culture conditions used here.

144 citations


Journal ArticleDOI
TL;DR: New techniques of human karyotyping have allowed us to define accurately the banding pattern of six new cases with partial duplication or deficiency of chromosome 13, correlating observed malformations and phenotypic features with specific chromosome regions.
Abstract: New techniques of human karyotyping have allowed us to define accurately the banding pattern of six new cases with partial duplication or deficiency of chromosome 13. It now seems possible to draw a rough map of chromosome 13, correlating observed malformations and phenotypic features with specific chromosome regions. Partial monosomy shows clinical features which are the antithesis of the corresponding trisomic phenotype: (Lejeune 1966).

99 citations


Journal ArticleDOI
01 Jun 2008-Methods
TL;DR: The following discussion describes the cytogenetic methods used in the laboratory to study cultured hESCs, along with recommendations for integrating these methods into a plan for routine cell line quality control.

96 citations


Journal ArticleDOI
01 Aug 2008-Genetics
TL;DR: It is reported that the threespine stickleback Y chromosome is heteromorphic and has suffered both inversions and deletion, suggesting that the process of sex chromosome evolution can occur rapidly following acquisition of a sex-determining region.
Abstract: To identify the processes shaping vertebrate sex chromosomes during the early stages of their evolution, it is necessary to study systems in which genetic sex determination was recently acquired. Previous cytogenetic studies suggested that threespine stickleback fish (Gasterosteus aculeatus) do not have a heteromorphic sex chromosome pair, although recent genetic studies found evidence of an XY genetic sex-determination system. Using fluorescence in situ hybridization (FISH), we report that the threespine stickleback Y chromosome is heteromorphic and has suffered both inversions and deletion. Using the FISH data, we reconstruct the rearrangements that have led to the current physical state of the threespine stickleback Y chromosome. These data demonstrate that the threespine Y is more degenerate than previously thought, suggesting that the process of sex chromosome evolution can occur rapidly following acquisition of a sex-determining region.

95 citations


Journal ArticleDOI
TL;DR: Findings confirm and extend previous observations and provide strong evidence for Xp212 as the site of the Duchenne and Becker loci and explain the altered banding pattern in these two cases.
Abstract: Lymphoblastoid cell lines have been established from nine female patients with Duchenne muscular dystrophy who had previously been reported to have chromosome translocations with breakpoints in the Xp21 region. A detailed cytogenetic comparison of prometaphase chromosomes in these cell lines revealed that six of the translocations had X chromosome breakpoints in the sub-band Xp212 and that one further breakpoint could be assigned to either Xp212 or Xp213. These findings confirm and extend previous observations and provide strong evidence for Xp212 as the site of the Duchenne and Becker loci. For the remaining two translocations the simplest explanation for the observed banding pattern is that the X chromosome breakpoint lies a few thousand kilobases away, in the sub-band Xp211. Other explanations which assume breaks in Xp212 combined with complex local chromosome rearrangements are also presented. It is also possible that the altered banding pattern in these two cases is due to the influence of local sequences on the staining or uncoiling properties of the chromatin.

Journal ArticleDOI
TL;DR: The interpretation of the extra chromosome as composed of two short arms of chromosome 12 is confirmed, using molecular methods, and restriction fragment length polymorphisms indicate that the two arms are identical, which is compatible with the hypothesis of an isochromosome 12p.
Abstract: Pallister-Killian syndrome is a dysmorphic syndrome characterized by a tissue-limited mosaicism: a majority of fibroblasts have 47 chromosomes with an extra small metacentric chromosome, whereas the karyotype of lymphocytes is normal. In this study, the interpretation of the extra chromosome as composed of two short arms of chromosome 12 is confirmed, using molecular methods. Furthermore, restriction fragment length polymorphisms indicate that the two arms are identical, which is compatible with the hypothesis of an isochromosome 12p. A new feature which may be important in understanding the mechanism of origin of the abnormality is described: the proportion of abnormal mitoses falls dramatically during long-term culture of fibroblasts.

Journal ArticleDOI
TL;DR: A study of the relationship between the degree of chromosome contraction and the frequency of band occurrence revealed that for all chromosome types the average band frequency increased with increasing chromosome elongation.
Abstract: The frequency and staining intensity of the dark bands were measured in 6985 trypsin G-banded human chromosomes, described by so-called band transition sequences which represent the chromosome banding patterns in a condensed quantitative way. In the haploid chromosome complement a maximum of 351 bands were registered: 181 white and 170 dark bands. The frequency with which bands occurred and the staining intensity of the bands differed considerably between the chromosome types. Among the dark bands the darker stained bands occurred more frequently than the lighter stained bands. A study of the relationship between the degree of chromosome contraction and the frequency of band occurrence revealed that for all chromosome types the average band frequency increased with increasing chromosome elongation. Twenty of the 23 dark bands chosen as landmarks by the Paris Conference (1971) occurred with high frequency and staining intensity. The remaining three landmarks occurred less frequently, due to fusion of dark and white bands, respectively. A study of global features showed, as expected, good agreement between chromosome length, area and density. There was good agreement between the centromeric indices determined by length and area, respectively, and no difference was found between contracted and elongated chromosomes, with the exception of the acrocentrics where elongated chromosomes showed higher centromeric indices than contracted chromosomes. Most often, the centromeric index by density differed considerably from the centromeric indices by length and area, respectively. The data presented here may be used in clinical cytogenetics as a supplement to the ISCN idiograms (ISCN 1978), as the band frequencies and staining intensities may help in identifying and characterizing specific bands.

Journal ArticleDOI
TL;DR: In this article, a phylogenetic framework was established from neighbour-net analysis of amplified fragment length polymorphism (AFLP) fingerprint data to assess directions and mechanisms of karyotype evolution in South American species by interpreting both newly obtained and previous data concerning rDNA localization in phylogenetic context.

Journal ArticleDOI
TL;DR: The findings indicate that sex chromosomes did not evolve at the family level in Caricaceae, and reinforce the theory that sex chromosome evolved at the species level in some lineages.
Abstract: *Summary Sex chromosomes in flowering plants, in contrast to those in animals, evolved relatively recently and only a few are heteromorphic. The homomorphic sex chromosomes of papaya show features of incipient sex chromosome evolution. We investigated the features of paired X- and Y-specific bacterial artificial chromosomes (BACs), and estimated the time of divergence in four pairs of sex-linked genes. We report the results of a comparative analysis of long contiguous genomic DNA sequences between the X and hermaphrodite Y (Y h ) chromosomes. Numerous chromosomal rearrangements were detected in the malespecific region of the Y chromosome (MSY), including inversions, deletions, insertions, duplications and translocations, showing the dynamic evolutionary process on the MSY after recombination ceased. DNA sequence expansion was documented in the two regions of the MSY, demonstrating that the cytologically homomorphic sex chromosomes are heteromorphic at the molecular level. Analysis of sequence divergence between four X and Yh gene pairs resulted in a estimated age of divergence of between 0.5 and 2.2 million years, supporting a recent origin of the papaya sex chromosomes. Our findings indicate that sex chromosomes did not evolve at the family level in Caricaceae, and reinforce the theory that sex chromosomes evolve at the species level in some lineages.

Journal ArticleDOI
TL;DR: An abnormal large chromosome was described by Gouw et al. (1964) in the karyotype (46 X‐X?) of a patient presenting a Turner‐like syndrome and appears to be the result of a fusion of two X chromosomes, short arms to short arms.
Abstract: An abnormal large chromosome was described by Gouw et al. (1964) in the karyotype (46 X-X?) of a patient presenting a Turner-like syndrome. The structure of this abnormal chromosome, re-studied with the new banding techniques (Quinacrine mustard fluorescence completed with micro-densitometric recordings, modified Giemsa and centromeric stainings) appears to be the result of a fusion of two X chromosomes, short arms to short arms. This chromosome is not dicentric but C-heterochromatin has been demonstrated on its long arms, at the probable centromeric region of the second X involved in the fusion. These findings, their relation to the clinical features and their possible mechanisms of formation, are discussed.

Journal ArticleDOI
23 Jan 2008-Genome
TL;DR: Results support the hypothesis that A. brevirostrum is a hexaploid species, probably of hybrid origin, and a model explaining speciation events occurring in sturgeons by hybridization, genome duplication, and diploidization is proposed.
Abstract: A karyotype analysis by several staining techniques was carried out on triplicate samples of the shortnose sturgeon, Acipenser brevirostrum. The chromosome number was found to be 2n = 372 +/- 6. A representative karyotype of 374 chromosomes was composed of 178 metacentrics/submetacentrics and 196 telocentrics/acrocentrics and microchromosomes. The signals of fluorescent in situ hybridization (FISH) with a HindIII satellite DNA probe were visible on 14 chromosomes. The signals obtained with a PstI satellite DNA probe appeared on 12 chromosomes. The FISH with a 5S rDNA probe revealed fluorescent signals on 6 chromosomes. These last results, compared with 2 signals in species with about 120 chromosomes and 4 in species with 240, support the hypothesis that A. brevirostrum is a hexaploid species, probably of hybrid origin. Based on these results, we propose a model explaining speciation events occurring in sturgeons by hybridization, genome duplication, and diploidization.

Journal ArticleDOI
TL;DR: Although the segregation behaviour of most chromosomes studied appeared to be mendelian, the segregation of chromosome No. 13 showed a lack of homozygotes without polymorphism, and possible mechanisms accounting for this effect are discussed.
Abstract: A study of the frequencies and segregation behaviour of fluorescent chromosome polymorphisms within a Dutch population is presented. The polymorphism patterns for chromosomes 1, 3, 4, 9, 13, 14, 15, 16, 21 and 22 were scored from 221 (108 female and 113 male) individuals with normal karyotype. Males and females were both found to carry an average of 4 polymorphic chromosomes per person, and approximately half of these were present in chromosomes No. 3 and 13. There was no significant difference between the frequencies per chromosome for the two sexes, and the data for chromosomes 3, 4, 14, 21 and 22 fitted a Hardy-Weinberg distribution. However, for chromosomes 13 and 15 an excess of heterozygotes and a lack of homozygotes was observed. Although the segregation behaviour of most chromosomes studied appeared to be mendelian, the segregation of chromosome No. 13 showed a lack of homozygotes without polymorphism. Possible mechanisms accounting for this effect are discussed.

Journal ArticleDOI
01 Feb 2008-Genetics
TL;DR: A high-precision cytological recombination map for the Eurasian common shrew is generated, the third such map produced in mammals, following those for humans and house mice, and suggests generality among mammals.
Abstract: The Eurasian common shrew (Sorex araneus L.) is characterized by spectacular chromosomal variation, both autosomal variation of the Robertsonian type and an XX/XY1Y2 system of sex determination. It is an important mammalian model of chromosomal and genome evolution as it is one of the few species with a complete genome sequence. Here we generate a high-precision cytological recombination map for the species, the third such map produced in mammals, following those for humans and house mice. We prepared synaptonemal complex (SC) spreads of meiotic chromosomes from 638 spermatocytes of 22 males of nine different Robertsonian karyotypes, identifying each autosome arm by differential DAPI staining. Altogether we mapped 13,983 recombination sites along 7095 individual autosomes, using immunolocalization of MLH1, a mismatch repair protein marking recombination sites. We estimated the total recombination length of the shrew genome as 1145 cM. The majority of bivalents showed a high recombination frequency near the telomeres and a low frequency near the centromeres. The distances between MLH1 foci were consistent with crossover interference both within chromosome arms and across the centromere in metacentric bivalents. The pattern of recombination along a chromosome arm was a function of its length, interference, and centromere and telomere effects. The specific DNA sequence must also be important because chromosome arms of the same length differed substantially in their recombination pattern. These features of recombination show great similarity with humans and mice and suggest generality among mammals. However, contrary to a widespread perception, the metacentric bivalent tu usually lacked an MLH1 focus on one of its chromosome arms, arguing against a minimum requirement of one chiasma per chromosome arm for correct segregation. With regard to autosomal chromosomal variation, the chromosomes showing Robertsonian polymorphism display MLH1 foci that become increasingly distal when comparing acrocentric homozygotes, heterozygotes, and metacentric homozygotes. Within the sex trivalent XY1Y2, the autosomal part of the complex behaves similarly to other autosomes.

Journal ArticleDOI
TL;DR: The purpose of this review is to present a summary of what is currently known about overall patterns of variation in karyology and genome size in salamanders within an evolutionary context.
Abstract: Salamanders (Amphibia: Caudata/Urodela) have been the subject of numerous cytogenetic studies, and data on karyotypes and genome sizes are available for most groups. Salamanders show a more-or-less distinct dichotomy between families with large chromosome numbers and interspecific variation in chromosome number, relative size, and shape (i.e. position of the centromere), and those that exhibit very little variation in these karyological features. This dichotomy is the basis of a major model of karyotype evolution in salamanders involving a kind of 'karyotypic orthoselection'. Salamanders are also characterized by extremely large genomes (in terms of absolute mass of nuclear DNA) and extensive variation in genome size (and overall size of the chromosomes), which transcends variation in chromosome number and shape. The biological significance and evolution of chromosome number and shape within the karyotype is not yet understood, but genome size variation has been found to have strong phenotypic, biogeographic, and phylogenetic correlates that reveal information about the biological significance of this cytogenetic variable. Urodeles also present the advantage of only 10 families and less than 600 species, which facilitates the analysis of patterns within the entire order. The purpose of this review is to present a summary of what is currently known about overall patterns of variation in karyology and genome size in salamanders. These patterns are discussed within an evolutionary context.

Journal ArticleDOI
TL;DR: In this paper, the authors performed chromosome mapping of sexual differentiation genes for Rana rugosa by FISH and found that three genes, AR, SF-1/Ad4BP and Sox3, were localized to both the ZW and XY chromosomes, and their locations were all different between the Z and W and between the X and Y.
Abstract: There are regional variations of sex chromosome morphologies in the Japanese wrinkled frog, Rana rugosa (2n = 26): heterogametic ZZ/ZW-type and XX/XY-type sex chromosomes, and two different types of homomorphic sex chromosomes. To search for homology between the ZW and XY sex chromosomes and the chromosome rearrangements that have occurred during sex chromosomal differentiation in R. rugosa, we performed chromosome mapping of sexual differentiation genes for R. rugosa by FISH. Three genes, AR, SF-1/Ad4BP and Sox3, were localized to both the ZW and XY chromosomes, and their locations were all different between the Z and W and between the X and Y. AR and SF-1/Ad4BP were located on the short arms of the W and X and the long arms of Z and Y, and Sox3 was mapped to the different locations on the long arms between the Z and W and between the X and Y, probably as a result of multiple rearrangements that occurred during the process of sex chromosome differentiation. However, the chromosomal locations of three genes were almost consistent between the Z and Y and between the W and X, indicating that the Z and Y chromosomes and the W and X chromosomes were respectively derived from the same origins. Dmrt1, which is located on avian sex chromosomes, was localized to autosomes in R. rugosa with both the ZW and XY sex chromosomes, suggesting that Dmrt1 might not be related to sex determination in this species.

Journal ArticleDOI
TL;DR: The difference between the two karyotypes on the diploid number and chromosome morphology can be explained by rearrangements of the fusion-fission type and also by pericentric inversions.
Abstract: In this study we examined the karyotypes of morphologically indistinguishable populations of the electric knifefish Gymnotus carapo sensu stricto from the Eastern Amazon of Brazil. These were identified unambiguously on the basis of external morphology, meristics, and pigmentation. Specimens from one of five localities exhibited a karyotype previously not documented for Gymnotus species in the Amazon basin: 2n = 40 (34M/SM+6ST/A). Samples from the other four localities exhibited a different karyotype: 2n = 42 (30M/SM+12ST/A), which we had previously described. Specimens from all five localities presented constitutive heterochromatin in the centromeric region of almost all chromosomes, including in the distal and interstitial regions. Staining with 4'6-Diamidino-2-phenylindole revealed C-positive banding. In both karyotypes the Nucleolar Organizer Region (NOR) was located on the short arm of pair 20, and Chromomycin A3 stained the NORs. Fluorescent in situ hybridization with telomeric probes showed an Interstitial Telomeric Sequence (ITS) in the proximal short arm of a metacentric pair in the 2n = 40 karyotype. The difference between the two karyotypes on the diploid number and chromosome morphology can be explained by rearrangements of the fusion-fission type and also by pericentric inversions. The presence of ITS in a metacentric pair of the 2n = 40 karyotype suggests that the difference in the diploid number of the karyotypes results from a fusion. The consistent 2n = 42 karyotype at four localities suggests an interbreeding population. However, because fusion-fission and pericentric inversions of this nature typically result in reproductive isolation, we speculate that the form with the 2n = 40 karyotype is a different species to that of the 2n = 42 form. Nonetheless, we did not observe evident differences in external morphology, meristics and pigmentation between the two forms, which suggest that they represent cryptic sympatric species in the G. carapo species complex. We speculate that the chromosomal speciation occurred recently, allowing insufficient time for the fixation of other differences following post-zygotic isolation.

Journal ArticleDOI
08 May 2008-Oncogene
TL;DR: Molecular analyses revealed that ring formation consistently generated novel FGFR1–PLAG1 gene fusions in which the 5′-part ofFGFR1 is linked to the coding sequence of PLAG1, and a novel mechanism by which FGFR 1 contributes to oncogenesis is revealed.
Abstract: We have previously identified a subgroup of pleomorphic salivary gland adenomas with ring chromosomes of uncertain derivation. Here, we have used spectral karyotyping (SKY), fluorescence in situ hybridization (FISH) and high-resolution oligonucleotide array-CGH to determine the origin and content of these rings and to identify genes disrupted as a result of ring formation. Of 16 tumors with rings, 11 were derived from chromosome 8, 3 from chromosome 5 and 1 each from chromosomes 1, 6 and 9. Array-CGH revealed that 10/11 r(8) consisted of amplification of a 19 Mb pericentromeric segment with recurrent breakpoints in FGFR1 in 8p12 and in PLAG1 in 8q12.1. Molecular analyses revealed that ring formation consistently generated novel FGFR1-PLAG1 gene fusions in which the 5'-part of FGFR1 is linked to the coding sequence of PLAG1. An alternative mechanism of PLAG1 activation was found in tumors with copy number gain of an intact PLAG1 gene. Rings derived from chromosomes 1, 5, 6 or 9 did not result in gene fusions, but rather resulted in losses indicative of the involvement of putative tumor suppressor genes on 8p, 5p, 5q and/or 6q. Our findings also reveal a novel mechanism by which FGFR1 contributes to oncogenesis and further illustrate the versatility of the FGFR1 and PLAG1 genes in tumorigenesis.

Journal ArticleDOI
TL;DR: In individuals in which all cells on cytogenetic analysis showed loss of the Y chromosome, there was a statistically significant increase in AML/MDS, suggesting that the absence of any normal-dividing cells in a bone marrow analysis may be indicative of AML-MDS.
Abstract: Context.—The clinical association between loss of the Y chromosome and acute myelogenous leukemia and myelodysplastic syndrome (AML/MDS) has been debated because both phenomena are related to aging. A prior publication suggests that loss of the Y chromosome in more than 75% of cells may indicate a clonal phenomenon that could be a marker for hematologic disease. Objective.—To evaluate the relationship between loss of the Y chromosome and AML/MDS. Design.—A retrospective review of cytogenetic reports of 2896 male patients ascertained from 1996 to 2007 was performed. Results were stratified based on the percentage of cells missing the Y chromosome and were correlated with patients' ages and bone marrow biopsy reports through logistic regression analysis with adjustment for age. Results.—Loss of the Y chromosome was found in 142 patients. Of these, 16 patients demonstrated myeloid disease, with 2 cases of AML and 14 cases of MDS. An increased incidence (P < .05) of AML/MDS was seen only in the group...

Journal ArticleDOI
TL;DR: The C-banded karyotypes of a number of species are sufficiently distinct to be of use for identification and the study of relationships, in combination with chromosome number, and number and morphology of marker chromosomes.
Abstract: Giemsa C-banded karyotypes of the 32 Hordeum L. species incl. all subspecies and cytotypes divide them into four groups by chromosome banding patterns. Most taxa have a rather similar pattern with a number of more or less randomly disposed C-bands at centromeric, intercalary, and distal positions. This agrees with their grouping with a common genome, H. H. brevisubulatum s.l. is normally grouped with genome H, but the banding patterns of the five subspecies deviate by having a low number of centromeric and intercalary bands only (patterns vary from having no to very conspicuous C-bands at the telomeres). H. bulbosum has most C-bands at the centromeres, and H. vulgare, most C-bands at centromeric and juxtacentromeric positions. The overall resemblance of the C-banding patterns of H. bulbosum and H. vulgare supports that both carry the same genome, I. H. marinum and H. murinum each have a deviating karyotype. The corresponding genomes are preliminarily referred to as ‘X’ and ‘V’. In combination with chromosome number, and number and morphology of marker chromosomes, the C-banded karyotypes of a number of species are sufficiently distinct to be of use for identification and the study of relationships. Most Hordeum species of the Americas have similar C-banded karyotypes at the respective ploidy level, questioning the biological relevance of referring them to different sections.

Journal ArticleDOI
TL;DR: Clinical features suggestive of Down's syndrome were also seen in a mildly retarded girl with a mosaic chromosome constitution (one cell line had an isochromosome for the long arm of chromosomes 21 and the other had a deletion of the short arm of chromosome 21).
Abstract: Five patients showing several stigmata of Down's syndrome and a partial trisomy of chromosome 21 are reported Three patients with only a moderate degree of mental retardation had an additional deleted chromosome 21; the characteristic dark G-band region of the long arm of 21 was missing In another patient with a typical Down's syndrome the G-band region and the distal portion of the long arm of 21 were present in excess and were translocated onto the short arm of 15 Clinical features suggestive of Down's syndrome were also seen in a mildly retarded girl with a mosaic chromosome constitution (one cell line had an isochromosome for the long arm of chromosome 21 and the other had a deletion of the short arm of chromosome 21) By correlating clinical and cytogenetic data on these patients, an attempt was made to analyse the phenotypic effects caused by the presence of excess amounts of different segments of chromosome 21

Journal ArticleDOI
TL;DR: Karyotype complexity appears to be a powerful predictor of prognosis, and the presence of trisomy 20 may be a marker of a more aggressive subset of this group of ESFT patients.
Abstract: Ewing's sarcoma family tumors (ESFT) are characterized by the presence of EWSR1-ETS fusion genes. Secondary chromosome changes are frequently described, although their clinical significance is not clear. In this study, we have collected and reviewed abnormal karyotypes from 88 patients with primary ESFT and a rearrangement of 22q12. Secondary changes were identified in 80% (70/88) of tumors at diagnosis. Multivariate analysis showed a worse overall and relapse free survival (RFS) for those with a complex karyotype (overall survival, P = 0.005; RFS, P = 0.04), independent of metastatic disease. Univariate survival analysis showed that a chromosome number above 50 or a complex karyotype was associated with a worse overall survival (>50 chromosomes, P = 0.05; complex karyotype, P = 0.04). There was no association between type of cytogenetic abnormality and the presence of metastatic disease at diagnosis. Univariate and multivariate survival analysis of a small subgroup with trisomy 20 indicated that trisomy 20 was associated with a worse overall and RFS. There was no difference in outcome associated with other recurrent trisomies (2, 5, 7, 8, or 12) or the common recurrent secondary structural rearrangements (deletions of 1p36, 9p12, 17p13, and 16q, and gain of 1q), although numbers were small. These data demonstrate the continued value of cytogenetics as a genome-wide screen in ESFT and illustrates the potential importance of secondary chromosome changes for stratification of patients for risk. Specifically, karyotype complexity appears to be a powerful predictor of prognosis, and the presence of trisomy 20 may be a marker of a more aggressive subset of this group. © 2007 Wiley-Liss, Inc.

Journal ArticleDOI
TL;DR: The results allow the formulation of a likely Canidae ancestral karyotype (CAK, 2n = 82), and reveal that at least 6–24 chromosomal fission/fusion events are needed to convert the CAK karyotypes of the modern canids.
Abstract: Canid species (dogs and foxes) have highly rearranged karyotypes and thus represent a challenge for conventional comparative cytogenetic studies. Among them, the domestic dog is one of the best-mapped species in mammals, constituting an ideal reference genome for comparative genomic study. Here we report the results of genome-wide comparative mapping of dog chromosome-specific probes onto chromosomes of the dhole, fennec fox, and gray fox, as well as the mapping of red fox chromosome-specific probes onto chromosomes of the corsac fox. We also present an integrated comparative chromosome map between the species studied here and all canids studied previously. The integrated map demonstrates an extensive conservation of whole chromosome arms across different canid species. In addition, we have generated a comprehensive genome phylogeny for the Canidae on the basis of the chromosome rearrangements revealed by comparative painting. This genome phylogeny has provided new insights into the karyotypic relationships among the canids. Our results, together with published data, allow the formulation of a likely Canidae ancestral karyotype (CAK, 2n = 82), and reveal that at least 6-24 chromosomal fission/fusion events are needed to convert the CAK karyotype to that of the modern canids.

Journal ArticleDOI
01 Jan 2008-Genetics
TL;DR: The results indicate that mt DNA insertions represent a major source of nuclear chromosomal variation in maize, and either that mtDNA is being incorporated or lost from the maize nuclear genome continuously.
Abstract: Mitochondrial DNA (mtDNA) insertions into nuclear chromosomes have been documented in a number of eukaryotes. We used fluorescence in situ hybridization (FISH) to examine the variation of mtDNA insertions in maize. Twenty overlapping cosmids, representing the 570-kb maize mitochondrial genome, were individually labeled and hybridized to root tip metaphase chromosomes from the B73 inbred line. A minimum of 15 mtDNA insertion sites on nine chromosomes were detectable using this method. One site near the centromere on chromosome arm 9L was identified by a majority of the cosmids. To examine variation in nuclear mitochondrial DNA sequences (NUMTs), a mixture of labeled cosmids was applied to chromosome spreads of ten diverse inbred lines: A188, A632, B37, B73, BMS, KYS, Mo17, Oh43, W22, and W23. The number of detectable NUMTs varied dramatically among the lines. None of the tested inbred lines other than B73 showed the strong hybridization signal on 9L, suggesting that there is a recent mtDNA insertion at this site in B73. Different sources of B73 and W23 were examined for NUMT variation within inbred lines. Differences were detectable, suggesting either that mtDNA is being incorporated or lost from the maize nuclear genome continuously. The results indicate that mtDNA insertions represent a major source of nuclear chromosomal variation.

Journal ArticleDOI
TL;DR: An adult female with severe mental retardation and dysmorphic features is described, and a de novo chromosomal aberration involving 8p was found, generating a duplication‐deficiency chromosome.
Abstract: An adult female with sever mental retardation and dysmorphic features is described. A de novo chromosomal aberration involving 8p was found. The karyotype was 46, XX, inv dup (8) (p12----p23.1). Dosage studies with the DNA probe D8S7, which is located at 8p23----8pter, showed that the patient was monosomic for this marker. Thus the de novo rearrangement generated a duplication-deficiency chromosome. The possible mechanisms of formation of this abnormal chromosome are discussed.