Molecular distinction between true centric fission and pericentric duplication-fission

Centromere (centric) fission, also known as transverse or lateral centric misdivision, has been defined as the splitting of one functional centromere of a metacentric or submetacentric chromosome to produce two derivative centric chromosomes. It has been observed in a range of organisms and has been ascribed an important role in karyotype evolution; however, the underlying mechanisms remain unknown. We have investigated four cases of apparent centric fission in humans. Two cases show a missing chromosome 22 or 18 that is replaced by two centric ring products, a third case shows two chromosome-10-derived telocentric chromosomes, whereas a fourth case involves the formation of two chromosome-18-derived isochromosomes. In all four cases, results of gross cytogenetic and fluorescence in situ hybridisation analyses were consistent with a simple centric fission event. However, detailed molecular analyses provided evidence in support of centromere duplication as a predisposing mechanism for the observed chromosomal breakage in two of the cases. Results for the third case are consistent with direct centric fission not involving centromere pre-duplication as the likely mechanism. Insufficient material has precluded the further study of the fourth case. The data provide the first molecular evidence for centromere pre-duplication as a possible mechanism to explain the classically assumed simple centric fission events in clinical cytogenetics, karyotype evolution and speciation.     

Post-zygotic breakage of a dicentric chromosome results in mosaicism for a telocentric 9p marker chromosome in a boy with developmental delay

Chromosomal rearrangements resulting in an inverted duplication and a terminal deletion (inv dup del) can occur due to three known mechanisms, two of them resulting in a normal copy region between the duplicated regions. These mechanisms involve the formation of a dicentric chromosome, which undergo breakage during cell division resulting in cells with either an inverted duplication and deletion or a terminal deletion. We describe a mosaic 3 year old patient with two cell lines carrying a chromosome 9p deletion where one of the cell lines contains an additional telocentric marker chromosome. Our patient is mosaic for the product of a double breakage of a dicentric chromosome including a centric fission. Mosaicism involving different rearrangements of the same chromosome is rare and suggests an early mitotic breakage event.     

基于比较核型分析方法追溯百合族 (百合科) 二型性核型的起源

百合族具有非常一致的二型性核型,由4条长染色体以及20条短染色体组成。目前有两个假说解释其二型性核型的来源,着丝粒横裂和多倍化。但是,具体是哪一种机制起主要作用仍然不清楚。根据文献以及自己的实验结果,我们整理并重新分析了百合亚科和美德兰亚科所有属的核型资料。比较核型分析结果表明,来自单条染色体的特征、染色体臂数、核型不对称性以及染色体的相对长度诸方面的证据都支持着丝粒横列是百合族核型进化的主要机制,但不能排除其它的机制也在起着作用,如臂间倒位和易位。臂间倒位和易位可能在郁金香族的核型进化中起着主要的作用。另外,本研究还报道了三个种的核型,粗茎贝母 (Fritillaria crassicaulis)、准格尔郁金香 (Tulipa suaveolens) 和尖果洼瓣花 (Gagea oxycarpa)。     

Maize centromere mapping: a comparison of physical and genetic strategies

Centromere positions on 7 maize chromosomes were compared on the basis of data from 4 to 6 mapping techniques per chromosome. Centromere positions were first located relative to molecular markers by means of radiation hybrid lines and centric fission lines recovered from oat-maize chromosome addition lines. These centromere positions were then compared with new data from centric fission lines recovered from maize plants, half-tetrad mapping, and fluorescence in situ hybridizations and to data from earlier studies. Surprisingly, the choice of mapping technique was not the critical determining factor. Instead, on 4 chromosomes, results from all techniques were consistent with a single centromere position. On chromosomes 1, 3, and 6, centromere positions were not consistent even in studies using the same technique. The conflicting centromere map positions on chromosomes 1, 3, and 6 could be explained by pericentric inversions or alternative centromere positions on these chromosomes.     

Chromosome-type aberrations induced in chromosome 9 after treatment of human peripheral blood lymphocytes with mitomycin C at the G(0) phase.

To determine the fate of chromosome aberrations induced primarily by clastogenic chemicals, aberrations of chromosome 9 in cultured human peripheral blood lymphocytes were analyzed after exposure to mitomycin C (MMC) at G(0) phase. Chromosome 9 painting by fluorescence in situ hybridization revealed that the translocation of 9p or 9q to another chromosome and the centric fragment representing the entire length of 9p were characteristically generated from chromatid-type aberrations involving the centromeric region of chromosome 9. These changes were not observed at 48 h after culture initiation, but persistently appeared at later stages (72-120 h postinitiation). Induction of centric fragments of 9p and micronuclei without the alpha satellite DNA of chromosome 9 suggested that most of the breaks were induced near the alpha satellite DNA locus on 9q. Modified patterns of chromosome 9 aberrations were also observed, being related to the copy number of the short or long arm of the chromosome. Such unbalanced karyotypes could remain in the lymphocyte genome over further cell divisions for at least 120 h after culture initiation, indicating that these aberrant cells can survive and that they could pose a health risk.     

Chromosome mosaicism in a zebra (Equus burchelli) abortus provides evidence for a different in-vivo/in-vitro survival of balanced and unbalanced karyotypes

A fibroblast culture from the skin of a zebra abortus recovered from a pedigree known, in part, to be segregating for a chromosome centric fission was karyotypically mosaic. Some cells were balanced for the fission and the others unbalanced, being deficient for the shorter fission product. Initially, the latter were in the majority but after continued culture (101 days) they were outgrown by the former. This finding either suggests a differential in-vivo/in-vitro fitness of the two cell types or a change in proportions resulting from some other mechanism.     

Evolution of a new chromosomal lineage in a laboratory population ofDrosophila through centric fission

Structural rearrangements of chromosomes have played a decisive role in the karyotypic evolution of species. It is also known that inversions, translocations, fusions, fissions, heterochromatin variations and other chromosomal changes occur as transient events in natural populations. Herein we report the occurrence of a rare event of centric fission of a metacentric chromosome in a laboratory population ofDrosophila, called Cytorace 1. This centric fission has been fixed in a sub-population of Cytorace 1, resulting in a new chromosomal lineage called Fissioncytorace-1.     

Chiasma frequency effects of structural chromosome change

Three structural chromosome changes in the plant Hypochoeris radicata 2n = 8 have been tested for their effects on chiasma formation: (1) centric fission of chromosome 1, (2) a whole arm exchange between chromosomes 1 and 3, and (3) an interchange between the long arm of chromosome 1 and the short arm of 2 which gives an effectively three-armed pachytene multiple. Mean chiasma frequencies were compared between full-sibs in families segregating for the rearrangements. In each family the chiasma frequency was higher in heterozygotes than basic homozygotes. The size of the chiasma increase is dependant on the number of additional potentially-paired segments in the complement at pachytene. Fission heterozygotes and 1/2 interchange heterozygotes, with one extra pairing region, both form about 0.45 more chiasmata per PMC than full-sib basic homozygotes. The 1/3 exchange, with two additional pairing regions, increases chiasma frequency by twice this, about 0.85 per PMC. Individuals homozygous for the centric fission maintain the raised chiasma level. The chiasma increase appears limited to the chromosome(s) affected by structural change with no detectable interchromosomal effect.     

Molecular mapping of the centromeres of tomato chromosomes 7 and 9

The centromeres of two tomato chromosomes have been precisely localized on the molecular linkage map through dosage analysis of trisomic stocks. To map the centromeres of chromosomes 7 and 9, complementary telo-, secondary, and tertiary trisomic stocks were used to assign DNA markers to their respective chromosome arms and thus to localize the centromere at the junction of the short and long arms. It was found that both centromeres are situated within a cluster of cosegregating markers. In an attempt to order the markers within the centric clusters, genetic maps of the centromeric regions of chromosomes 7 and 9 were constructed from F₂ populations of 1620Lycopersicon esculentum × L. pennellii (E × P) plants and 1640L. esculentum × L. pimpinellifolium (E × PM) plants. Despite the large number of plants analyzed, very few recombination events were detected in the centric regions, indicating a significant suppression of recombination at this region of the chromosome. The fact that recombination suppression is equally strong in crosses between closely related (E × PM) and remotely related (E × P) parents suggests that centromeric suppression is not due to DNA sequence mismatches but to some other mechanism. The greatest number of centromeric markers was resolved in theL. esculentum × L. pennellii F₂ population. The centromere of chromosome 7 is surrounded by eight cosegregating markers: three on the short arm, five on the long arm. Similarly, the centric region of chromosome 9 contains ten cosegregating markers including one short arm marker and nine long arm markers. The localization of centromeres to precise intervals on the molecular linkage map represents the first step towards the characterization and ultimate isolation of tomato centromeres.     

Role of heterochromatin during preferential 9q;22q translocation in chronic myelogenous leukemia

The secondary constriction region (h) of human chromosome 9 was evaluated in 55 chronic myelogenous leukemia (CML) patients with respect to its size and position. Each case was examined by C-banding and distamycin A-4,6-diamidino-2-phenylindole techniques for the expression of the h regions. When one h region of chromosome 9 was larger, it was more frequently involved in the reciprocal translocation with chromosome 22. In addition, there was a higher incidence of pericentric inversions in the h regions in the translocated chromosome 9 when compared with normal homologues. The role of the constitutive heterochromatin of chromosome 9 as a possible influencing factor during 9q;22q translocation in CML is suggested.     

The role of the Robertsonian rearrangements in the origin of the XX/XY1Y2 sex chromosome system and in the chromosomal differentiation in Harttia species (Siluriformes, Loricariidae)

Harttia is a genus of the subfamily Loricariinae that posses a broad chromosomal variation. In addition to interspecific karyotype diversity within this group, a multiple sex chromosome system, XX/XY₁Y₂, has been described for Harttia carvalhoi. Thus, this study aimed to determine the role of chromosomal rearrangements in karyotype differentiation in Harttia by classical and molecular cytogenetic procedures. The results show that Robertsonian rearrangements have a prominent role in the chromosomal diversification of the species analysed, which initially leads to hypothesize a diploid number reduction in Harttia torrenticola and H. carvalhoi. The metacentric chromosome 1, shared between H. torrenticola and H. carvalhoi, could have originated from centric fusions from the ancestral karyotype. A centric fission event associated with the first metacentric pair allowed for the origination of a multiple sex chromosome system XX/XY₁Y₂, specific to H. carvalhoi. This study highlights the relevance of Robertsonian rearrangements in karyotypic differentiation of the species studied and demonstrates that the occurrence of a centric fission, as opposed to a previously hypothesised chromosome fusion, is directly implicated in the origin of the sex chromosome system of H. carvalhoi.     

Homologous fission event(s) implicated for chromosomal polymorphisms among five species in the genus Equus

The genus Equus is unusual in that five of the ten extant species have documented centric fission (Robertsonian translocation) polymorphisms within their populations, namely E. hemionus onager, E. hemionus kulan, E. kiang, E. africanus somaliensis, and E. quagga burchelli. Here we report evidence that the polymorphism involves the same homologous chromosome segments in each species, and that these chromosome segments have homology to human chromosome 4 (HSA4). Bacterial artificial chromosome clones containing equine genes SMARCA5 (ECA2q21 homologue to HSA4q31. 21) and UCHL1 (ECA3q22 homologue to HSA4p13) were mapped to a single metacentric chromosome and two unpaired acrocentrics by FISH mapping for individuals possessing odd numbers of chromosomes. These data suggest that the polymorphism is either ancient and conserved within the genus or has occurred recently and independently within each species. Since these species are separated by 1-3 million years of evolution, this polymorphism is remarkable and worthy of further investigations.     

Integrative study on chromosome evolution of mammals, ants and wasps based on the minimum interaction theory

There is well-known evidence that in many eukaryotes, different species have different karyotypes (e.g. n=1-47 in ants and n=3-51 in mammals). Alternative (fusion and fission) hypotheses have been proposed to interpret this chromosomal diversity. Although the former has long been accepted, accumulating molecular genetics evidence seems to support the latter. We investigated this problem from a stochastic viewpoint using the Monte Carlo simulation method under the minimum interaction theory. We found that the results of simulations consistently interpreted the chromosomal diversity observed in mammals, ants and wasps, and concluded that chromosome evolution tends to evolve as a whole toward increasing chromosome numbers by centric fission. Accordingly, our results support the fission hypothesis. We discussed the process of chromosome evolution based on the latest theory of the molecular structure of chromosomes, and reconfirmed that the fission burst is the prime motive force in long-term chromosome evolution, and is effective in minimizing the genetic risks due to deleterious reciprocal translocations and in increasing the potential of genetic divergence. Centric fusion plays a biological role in eliminating heterochromatin (C-bands), but is only a local reverse flow in contrast to the previously held views.     

Stable telocentric chromosomes produced by centric fission in chinese hamster cells in vitro

Metaphase examination of pseudodiploid Chinese hamster cells revealed that spontaneous breaks or fission occurred rather frequently (2.9%) at the centromeric regions of subtelo- or metacentric chromosomes, resulting in the production of telocentric chromosomes. The centromeric fission appeared to occur in every member of the chromosome complement. An attempt was made to isolate cells possessing thus derived telocentrics from the cell population and gave two clonal lines which were retaining one and two telocentric chromosomes, respectively. Both banding and labeling patterns of these chromosomes indicated unequivocally their X chromosome origin. They were transmitted successively to the daughter cells during a 3-month culture period, showing no tendency to fuse to produce a metacentric chromosome.Contribution No. 897 from the National Institute of Genetics, Japan.     

Three chromosomes' (7;9;22) rearrangement and the origin of the Philadelphia chromosome

Summary A woman with chronic myelocytic leukemia had the Philadelphia chromosome and a complex four-break—three-chromosome rearrangement. The q32q34 portion of chromosome 9 is translocated to band q22 of chromosome 7, and at the end of this segment is attached the deleted q11 qter portion of chromosome 22. A review of 12 cases of the Philadelphia chromosome originating by the rearrangement of three or more chromosomes reveals that chromosomes 9 and 22 are always involved, while the third chromosome is a different one in each case. We discuss the hypothesis that the 22q segment is always specifically attached to band 9q34 wherever this portion of 9q is transposed.Address for offprint requests: Prof. M. Fraccaro, Gruppo Euratom, Via Forlanini, 14, I-27100 Pavia, Italy     

着丝粒横裂和着丝粒并合及其在高等植物染色体进化中的意义

本文讨论了着丝粒横裂和并合及其在高等植物染色体进化中的意义。着丝粒横裂和着丝粒并合是两个矛盾又辩证统一的过程,是染色体的基本变异形式之一,它们同时影响着植物类群的染色体基数、核型对称性、连锁关系、交叉频率和位点等细胞遗传学的重要方面.从而在高等植物染色体进化中起着重要作用,着丝粒和端粒的复制模型为着丝粒的横裂与并合提供了可能的机理,但尚待直接的生物化学证据的证实,原始基数的确定是判别着丝粒横裂与并合的关键。     

Phenotypic and cytogenetic spectrum of 9p trisomy

Trisomy 9p is one of the most frequent autosomal anomalies compatible with long survival rate. The spectrum of clinical severity in trisomy 9 roughly correlates with the extent of trisomic chromosome material. Trisomy 9p is a clinically well delineated syndrome and of all stigmata craniofacial dysmorphism is most specific. In this study we report five cases with de novo trisomy 9p. The study aimed at the identification of the genotype/phenotype correlations in patients with different breakpoints. GTG banding, DAPI stain, whole chromosome paint, centromere, telomere and 9p21 specific locus probes demonstrated that partial trisomy 9p in case 1 was due to isochromosome 9p with translocation of the long arm of re-arranged chromosome 9 onto the short arm of chromosome 13, cases 2 and 3 had intrachromosomal duplication of the short arm of chromosome 9 [dup(9)(p21p24)], case 4 had "classical" 9p trisomy and case 5 had duplication of whole short arm and part of the long arm of chromosome 9 (partial 9 trisomy). Although cases 1 to 4 had trisomy involving 9p, cases 1 and 2 exhibited the classical clinical manifestations of 9p trisomy, while cases 3 and 4 had additional features overlapping with Coffin-Siris syndrome. The present study strengthens the association of Coffin-Siris syndrome and 9p, the significance of such observations may point to possible gene location of Coffin-Siris syndrome on 9p. Case 5 had additional manifestations more than those typical of trisomy 9p which could be due to duplication of 9q21 region. Wide gap between 1st and 2nd toes, observed in the studied cases, can be added to the phenotype of this trisomy. Three of our cases had brain malformations, case 3 had dilated ventricles with hypogenesis of corpus callosum, case 4 had agenesis of corpus callosum, and case 5 had Dandy-Walker malformation. We also suggest that dosage effects of genes located in 9pter-q22 contribute to the etiology of Dandy-Walker syndrome. We recommend MRI studies as a routine in all cases with trisomy 9p.     

Alteration by centric fission of the diploid chromosome number in Vicia faba L.

An individual with a diploid chromosome complement of 2n=14 instead of 2n=12 is deseribed for the broad bean Vicia faba L. This karyotypic deviation resulted from centromere splitting of the wildtype metacentric satellite chromosome pair as demonstrated by Giemsa banding pattern. It is the first case of centric fission observed in this species. Our data support the hypothetic mechanism of Robertsonian rearrangements suggested by Holmquist and Dancis (Genetica 52–53: 151–163, 1980).     

Karyology and phylogeny of some Mesoamerican species of Zamia (Zamiaceae)

Chromosome numbers and karyotypes of four species of Zamia L. (Zamiaceae) are described. Plants of Z. manicata from Colombia are 2n = 18 with eight metacentric (M), four submetacentric (S), two acrocentric (A), and four telocentric (T) chromosomes. Plants of Z. ipetiensis from Panama are 2n = 23 with 3M + 4S + 2A + 14T. Plants of Z. cunaria from Panama have two different chromosome numbers, 2n = 23 with 3M + 4S + 2A + 14T and 2n = 24 with 2M + 4S + 2A + 16T. Plants of Z. acuminata from Costa Rica and Panama are 2n = 24 with 2M + 4S + 2A + 16T. On the basis of the occurrence of a one-to-two-ratio in the variation of M- and T-chromosome numbers in the karyotypes, centric fission or fusion are considered for their potential involvement in the chromosome variation of these plants. Data deriving from morphology and karyology, interpreted in a cladistic framework, suggest that centric fission rather than centric fusion is involved in the karyotype diversification of the four species and their closest Mesoamerican allies.     

Spontaneous fragility of an abnormally wide secondary constriction region in a human chromosome No. 9

Summary In an infant with clinically and cytologically typical Down's syndrome a chromosome No. 9 was found exhibiting an exceptionally large paracentric constriction which proved to be spontaneously fragile. In cells in which this chromosome was broken the centric portion was present whereas the acentric fragment was absent. A No. 9 chromosome with identical morphology was found in the karyotype of the father but no fragility was evident. Autoradiography revealed pronounced late replication in the constriction region, suggesting a duplication or insertion of heterochromatic material. Clinically there was no evidence for any phenotypic expression of this cytological anomaly.Supported in part by the Swiss National Foundation