Isochromosome Formation Research Articles

Cytogenetic study of ten carcinomas of the bladder: Involvement of chromosomes 1 and 11

In direct preparations of ten untreated transitional cell carcinomas of the bladder, chromosomes #1 and #11 were most frequently involved in structural changes (in at least seven tumors each). Three tumors had one or two 11p− chromosomes, and, in other tumors, chromosome #11 had taken part in translocations or isochromosome formation, which, except in one tumor, resulted in a loss of short arm material. Also, there was a tendency for the presence of fewer than expected normal chromosomes #11. Chromosome #1 anomalies are common in most types of tumor; however, chromosome #11 abnormalities, particularly the loss of short arm material, are not common and may thus characterize carcinoma of the bladder, a finding that is of interest in view of the location of an oncogene, c-Ha- ras1, on 11p. Translocations probably involved chromosome #17 in four tumors. Structurally changed chromosomes #3 were seen in four tumors, including one or two 3q− chromosomes in two or possibly three tumors.

Evolution of an octacentric isochromosome in mouse L-cells.

A sub-line of mouse L-cells exhibits a rather long biarmed chromosome which shows eight C-bands. Incorporation of BrdU for less than one cell cycle results in lateral asymmetry in the pericentromeric region as well as in the two arms. These regions of asymmetry correspond to four C-banding regions in each arm. Before it is fully condensed at metaphase, and particularly upon treatment with Hoechst, this chromosome expresses eight primary constrictions. Hence it is an octacentric. Presumably, it originated from tandem rejoinings between the short arms and the long arms of four chromosomes followed by the formation of an isochromosome. Since it is present in almost 100% cells, this octacentric chromosome must divide equationally at every cell division.

Evidence for an indirect effect of radiation on mammalian chromosomes. II. UV-induced isochromosome formation in cell hybrids

Cell fusion has been used to test the hypothesis that chromosomes may be damaged indirectly by UV light, as well as by direct interaction with DNA. Hybrids were found to contain isochromosomes of mouse origin, whose frequency increased as the dose of UV delivered to the hamster cell parent was increased. This unusual type of aberration was shown to be induced also by direct UV irradiation of mouse or hybrid cells. These results suggest that UV light has a hitherto undiscovered indirect effect on chromosome integrity, mediated by some irradiated cell component.

The origin, structure, and clinical significance of satellited marker chromosomes

Satellited marker chromosomes are occasionally found in cytogenetic preparations, and significantly in amniotic fluid cultures. The question of their origin and significance therefore arises. These chromosomes arise at least partially from the acrocentric chromosomes, by reciprocal translocation, isochromosome formation, U-type exchange, or minor heterochromatic variation. Eighteen cases involving satellited markers were examined, using multiple banding techniques. These were shown to originate from reciprocal translocations (10 cases), isochromosomes (7 cases), and heterochromatic variation (1 case). The study demonstrated that in reciprocal translocations the marker in unbalanced form leads to a phenotypic effect. In the case of isochromosomes, a dicentric bisatellited marker has a phenotypic effect, but monocentric satellited markers present as extra chromosomes have no effect, apart from a case where male fertility was impaired. It was concluded that knowledge of the structure, as determined by multiple banding techniques, and origin, as determined by parental studies, of satellited marker chromosomes, enables an assessment of their phenotypic consequences to be made. Satellited marker chromosomes are occasionally found in cytogenetic preparations, and significantly in amniotic fluid cultures. The question of their origin and significance therefore arises. These chromosomes arise at least partially from the acrocentric chromosomes, by reciprocal translocation, isochromosome formation, U-type exchange, or minor heterochromatic variation. Eighteen cases involving satellited markers were examined, using multiple banding techniques. These were shown to originate from reciprocal translocations (10 cases), isochromosomes (7 cases), and heterochromatic variation (1 case). The study demonstrated that in reciprocal translocations the marker in unbalanced form leads to a phenotypic effect. In the case of isochromosomes, a dicentric bisatellited marker has a phenotypic effect, but monocentric satellited markers present as extra chromosomes have no effect, apart from a case where male fertility was impaired. It was concluded that knowledge of the structure, as determined by multiple banding techniques, and origin, as determined by parental studies, of satellited marker chromosomes, enables an assessment of their phenotypic consequences to be made.

Primary Amenorrhea with a New Mosaic 46,XXqi/47,XXqi Xp-—Consideration on the X isochromosome formation and X chromosome inactivation

A case of Turner's syndrome was found to be 46,XXqi/47XX,qi Xp-, a new mosaic. The origin of such a mosaic, the formation of the Xq isochromosome using the C-banding technique, and the X chromosome inactivation are discussed. The Xq isochromosome was apparently monocentric, but probably with two strictly close centromeres. The inactivated X seemed to be the Xqi or the normal X alternatively.

Twins in the sibships and parental sibships of women with Turner's syndrome.

The twin birth frequency in the sibships of 45 females with Turner's syndrome was 3.7% for the 21 females with 45,X and 5.7% for the 24 with other karyotypes. The 5.7% is significantly higher than the expected mean frequency of 1.4% in the Danish population from 1900 to 1974. The twin birth frequency in the sibships of the mothers of the 24 females with karyotypes other than 45 X was 4.7% which is also significantly higher than expected. The twin birth frequency in the sibships of the 21 mothers of 45,X females did not deviate significantly from the expected frequency, and nor did that of the father's sibships. It is concluded that these findings indicate that there might be an association between the increased risk of X chromosome aberration in the progeny due to mitotic non-disjunction, isochromosome or ring chromosome formation on one hand, and twin formation on the other hand. Such X chromosome aberration and twin formation might thus have some common aetiological factors, and some of the possibilities are discussed.

The biarmed chromosomes of mouse cell line LMTK-.

Staining for fluorescent bands and centromeric heterochromatin showed that normal mouse chromosomes could be identified as specific arms in most of the biarmed chromosomes of the mouse cell line LMTK–. Seven marker chromosomes were also characterized. The karyotype was heterogeneous with an average of 9.4 biarmed chromosomes per cell. Five specific biarmed chromosomes were present in at least 90% of the cells examined. The results indicate the presence of both relatively stable and highly variable components in the in vitro karyotype. Evidence is presented which indicates that the biarmed chromosomes have been formed by reciprocal translocation, centric fusion with retention of both centromeres, and centromeric misdivision with isochromosome formation.

Instability of the maize B chromosome

The B (9) chromosome of maize exhibits a very ordered type of instability at the second pollen mitosis, when nondisjunction may reach a level of 95%. Much less commonly the chromosome is unstable during early development of the kernel. Instability in the kernel produces recessive sectors in either the endosperm or the sporophyte, reflecting the absence of dominant markers carried by the B (9). The causes of B (9) loss in the endosperm and the sporophyte were investigated for the two observable classes of sectoring: fractional loss (single event) and multiple loss (mosaic pattern). The fractional class represents isochromosome formation by the B (9) (Carlson, 1970, 1971). Data presented here suggest that the isochromosome is a by-product of telocentric formation at the second pollen mitosis, and does not arise directly from the B (9) chromosome. The chromosomal basis for the mosaic pattern of B (9) loss is not completely known. However, one class of mosaic kernels displays a heritable instability of the B (9) chromosome which apparently results from ring chromosome formation by the B (9). The time of origin of the ring B (9) chromosome is prior to the second pollen mitosis, since the unstable chromosome generated in the male parent is transmitted to both the endosperm and the sporophyte. Finally, a genetic factor controlling B (9) stability in the developing endosperm has been found. A single plant (1818-1), crossed as a female parent to a B (9)-containing stock, induced a mosaic pattern of B (9) loss in the endosperm at a very high rate. The characteristics of this plant are being investigated.

Trisomy-18 syndrome caused by translocation or isochromosome formation. A case report with bibliography.

Trisomy-18 syndrome caused by translocation or isochromosome formation. A case report with bibliography.

Isochromosome for the short arm of X, a human 46, XXpi syndrome.

SUMMARYCytogeetical and clinical findings in a 17 year‐old female with te karyotype 46, XXpi are presented. The patient was 159 cm tall and had never menstruated. The gonads were not palpable and secondary sex characteristics were poorly developed. She had no somatic sgns of Turner's syndrome apart from a renal anomaly. The abnormal X chromosome could be identified as an Xpi by its characteristic fluorescence patterns and Giemsa staining properties after the ASG procedure. Autoradiography showed it to be the latest‐labelling chromosome in nearly all cells. Sex chromatin bodies were normal in number and decreased in size (79% of normal). These findings, taken with the incomplete data from two presumptive XXpi cases reported by others, indicate that the karotype 46, XXpi produces a clinical picture distinguishable from Turner's syndrome.The proposita and her father were Xg(a+), and her mother Xg(a−), indicating paternal derivation of the normal X chromosome. Hence the Xpi appears to be of maternal origin. Other interpretations are possible.The findings lend added support to the hupothesis that genes controlling gonodal development are carried in both Xp and Xq, whereas those affecting stature are in Xp but probably not in Xq.It is proposed that at isochromosome formation Xqi is far more likely to be produced than Xpi. This may be because breakage preferentially occcurs at the short‐arm end of the centromere region or in the short arm itself, as indicated by the existence of presumptive dicentric Xqi chromosomes.

Nondisjunction and isochromosome formation in the B chromosome of maize

Bianchi et al. (1961) found that sectored losses of B-translocation chromosomes occur at a significant rate during early development of the endosperm and sporophyte. The losses were attributed to nondisjunction of the chromomosome, since B type chromosomes are known to undergo nondisjunction at the second pollen mitosis. Sector formation was further analyzed in the present paper, using the translocation, TB-9b. It was found that losses of the B9 chromosome during early endosperm mitoses occur only if the 9B chromosome is present. In addition, sectors are produced in the sporophyte only if the 9B and B9 chromosomes are inherited from the male parent. Both of these findings suggest that nondisjunction is indeed responsible for the B9 losses (see text). However, cytological observation of sectored plants demonstrates that isochromosome formation, rather than nondisjunction, produces most B9 losses in the sporophyte. The conflicting results can be reconciled by assuming that the same basic event, perhaps “stickiness” of the B9 chromosome, produces nondisjunction at the second pollen mitosis and isochromosome formation in the developing sporophyte. Observation of the isochromosome in pachytene reveals that a heterochromatic region corresponding to the short arm of the normal B9 is missing. The normal B9 chromosome is, therefore, an acrocentric chromosome.

Crossing-over and the centromere.

Experiments with human lymphocytes and H.Ep.2 human neoplastic cells treated with tritiated thymidine yielded evidence which suggests that sister chromatid crossing-over may occur in the centromere. As a result of this study a possible mechanism of isochromosome formation is postulated.

Structural differentiation of the kinetochore in rye and Agapanthus

(1) The kinetochore of the pachytene chromosomes of Secale cereale was found to consist of the following components(starting from one end): a pair of almost unstained fibrillae, a chromomere pair, a pair of deeply stained fibrillae, another chromomere pair and again an almost unstained fibrilla pair. In the interior zone of the kinetochore, which is formed by the deeply stained fibrilla pair, one and two chromomeres have been observed. The presence of these chromomeres demonstrates that the interior zone has also a compound structure, consisting of minor chromomeres that become visible under particular conditions. In some of the pachytene chromosomes of Agapanthus umbellatus two chromomere pairs of different size united by a deeply stained fibrilla pair and connected with the arms by almost unstained fibrilla pairs were found at the kinetochore. This structural pattern has a characteristic egg-shaped appearance. (2) The kinetochore structure is essentially the same in both species, but it differs in the degree of pairing and size relations of the kinetochoric chromomeres. (3) This well differentiated structure of the kinetochore provides a material basis which allows for a comprehensive picture of the formation of kinetochores with new structures and properties. Such kinetochores have been obtained in rye and they represent rearrangements of the original components both in respect to their number and relative position. (4) The two halves of the kinetochore of rye were found to be not only morphologically alike and symmetrical but to be also essentially similar in function. These results are in very good agreement with the easy formation and survival of iso-chromosomes in rye as well as with the successful behaviour of chromosomes with a deleted kinetochore obtained also in rye.

MUTATIONS IN POLYPLOID CEREALS: III. THE CYTOGENETICS OF COMPACTOID WHEATS

The compactoid mutants of wheat are, both phenotypically and cytogenetically, the reciprocals of the speltoid mutations. They are determined by excess dosages of the long arm of the C chromosome. This may be through primary polysomy involving the whole C chromosome, or through formation of isochromosomes comprising two long arms of C, or through fragmentation and the presence of excess telokinetic long arms of C. The short arm affects the phenotype slightly in the opposite direction. Other chromosomes present in excess may compensate for lack of C, especially in determining fertility. Most of the compactoid, subcompactoid, and subnormal types are of low fertility but the genetic data obtainable agree with cytological expectation. Very different progeny types and segregation ratios result from compactoid mutants that may be phenotypically and genically similar but different in the structure of their C chromosome constitution. There are three main types of subcompactoids and many subsidiary ones. Primary trisomic subcompactoids usually give only normal, subcompactoid, and compactoid progeny while a secondary type gives normals, subnormals, het speltoids, subcompactoids, and compactoids as regular segregates, besides other abnormal offspring. The data have significance for general problems of polyploid cytogenetics and the systematics of polyploid cereals.

The behavior of isochromosomes and telocentrics in wheat.

Genetic tests with chromosome IX of common wheat showed 13.3% formation of isochromosomes from telocentrics as against 7.0% for the same long arm of normal IX, and 7.0% formation of telocentrics from each arm of iso-IX instead of 10.8% from the same arm of normal IX. The differences are not significant statistically. No differences in frequency of formation of isochromosomes were found among 16 independently produced telocentrics for the long arm of chromosome IX. Somatic loss of both telocentrics and isochromosomes for chromosome IX and other wheat chromosomes has been observed, with loss of the telo being somewhat more frequent. A telocentric gave rise, to an isochromosome somatically. and isochromosomes added a telocentric. Two complex aberrations involving loss and duplication of parts of arms were observed, one of a telo and one of an iso; but these aberrations probably occurred at meiosis.