Unequal nondisjunction frequencies of trivalent chromosomes in male mice heterozygous for two Robertsonian translocations

Robertsonian (Rb) translocation heterozygosity may cause pairing problems during prophase and segregation irregularities at anaphase of meiosis I. These stages of meiosis I were studied in male mice doubly heterozygous for the two Rb chromosomes Rb(9.19)163H and Rb(16.17)8Lub. At pachytene both Rb chromosomes similarly showed pairing irregularities like unpaired segments. However, highly different nondisjunction frequencies of chromosomes forming the respective trivalents were found. The nondisjunction frequency of the Rb8Lub trivalent chromosomes was about 40%, whereas a very low frequency of nondisjunction was found in combination with the Rb163H trivalent. Since both trivalents were together in the same cell, differences in kinetochore function are assumed to be responsible for the diverse frequency of nondisjunction.     

Homozygous Robertsonian translocations in a fetus with 44 chromosomes

Summary We report the unique finding of a human fetus with 44 chromosomes with homozygous 14;21 translocations. This fetus appeared phenotypically normal but the long-term neurodevelopmental outcome had this pregnancy continued could not be predicted. We speculate one 14;21 translocation was inherited from her father and one arose de novo being maternal in origin. A previous sibling with psychomotor retardation has an abnormal chromosome complement of 45,XX,dup(7)(q21pter), t(14;21)(p11;q11). The mother's underlying disease, systemic lupus erythematosis (SLE), and her prior chemotherapy may have contributed to the appearance of these chromosome aberrations. It is interesting that although 14;21 translocations are among the commonest structural chromosome rearrangements in man, there are no previous reports in newborn surveys of a child with 44 chromosomes resulting from the mating of two identical Robertsonian translocation carrier parents.     

Chiasma frequency and position in male and female mice of chromosomes involved in homozygous and heterozygous translocations and tertiary trisomy

Chiasma frequency and position were analyzed at a predominantly late diplotene-diakinesis stage of the first meiotic division in oocytes and spermatocytes from T(1;13)70H homozygotes and heterozygotes, T(2;8)26H heterozygotes and from Ts(I¹³)70H tertiary trisomics of the mouse, Mus musculus. For T70H/T70H, the 13¹ long marker bivalent was studied and for the other karyotypes, analysis was confined to the multivalent configurations adopted by the rearranged chromosomes and their homologues. For the 13¹ bivalent, the chiasma frequency tended to be increased in the female. For the T26H and the T70H multivalents, the chiasma frequencies were higher in the female, largely due to the much higher values in the short interstitial segments. This observed enhancement has been attributed to pairing differences rather than to differences in chiasma forming capability. Both in the telomeric region of the 13¹ bivalent and in the short translocated segments of the reciprocal translocation and tertiary trisomic multivalents, females showed fewer chiasmata than males. The determinations of chiasma position in the 13¹ bivalent indicated chiasma interference with respect to position, leading to clustering of chiasmata somewhat beyond the centromere and towards the telomere of this chromosome.     

Kinetics of oogenesis in mice heterozygous for Robertsonian translocations

The total number of oocytes at different postmating time intervals (18-40 days) was determined in mice homozygous and heterozygous for different Robertsonian (Rb) translocations, of both laboratory and feral origin. The number of oocytes was lower in heterozygous than in homozygous mice throughout the period studied. Independently of the genetic background (i.e. laboratory or feral), structural heterozygosity had a progressive detrimental effect on oocyte numbers: open, or chain diakinetic configurations had a greater detrimental effect than close, or ring, configurations. The genetic background, however, affected the ovarian constitution in terms of the total number of germ cells, which are more numerous in laboratory than in feral mice. The kinetics of oogenesis seems to be faster in feral than in laboratory mice. At the light of the data here presented, and of those already available from the literature on male and female gametogenesis in conditions of structural heterozygosity, it appears that factors other than unsaturation of pairing sites or interference with pachytene X-chromosome inactivation have to be considered. In the wild, the reduced oocyte numbers in Rb heterozygous female can contribute to the retention of isolated populations in contact zones.     

Trivalent behavior during prophase I in male mice heterozygous for three Robertsonian translocations: an electron-microscopic study

A synaptonemal complex (SC) analysis was carried out in male mice heterozygous (CHT/+) for three Robertsonian translocations. All pachytene preparations studied showed the presence of three trivalents. At early pachytene, the nonhomologous centromeric regions of the acrocentric chromosomes were unpaired. Heterosynapsis subsequently took place with complete pairing of the trivalents. Association between one of the three trivalents and the sex vesicle was observed in 30.4% of the nuclei. Association between the unpaired regions of two trivalents was present in 14.4% of the cells, suggesting that the relationship between unpaired regions of structural rearrangements and the X-Y bivalent may simply reflect the tendency of unpaired regions to establish end-to-end associations or heterosynapses among them, which are usually resolved during the pachytene stage of prophase I. Since the sex bivalent always has unpaired regions, these associations often affect the sex chromosomes.     

Robertsonian translocations introduced into an island population of house mice

In April 1982, 77 house mice from the Orkney Island of Eday were released by R. J. Berry and his associates on the Isle of May, Firth of Forth. The Isle of May had a standard house mouse karyotype (2n = 40), while those from Eday are homozygous for three centric fusions (2n = 34). Within 18 months of introduction (September 1983), each centric fusion had increased in frequency from an estimated starting value of 8% to a value close to 50%, and they were segregating in accordance with Hardy–Weinberg expectations. In essence, the transformed population was behaving as a panmictic unit. The frequencies of introduced chromosomes had apparently stabilized by September 1986 with values around 65% for all three fusions. The cytogenetic data obtained in the Isle of May introduction experiment accord well with data for single gene loci (represented by allozyme data) and morphometric data. Male Eday–May F1 hybrids were found to have a low frequency of non-disjunction (13%). This study is unusual because the successful introduction of mice into an established population, and the introgression and stabilization of three centric fusions, could not have been predicted from previous studies on the mouse.     

Nonhomologous synapsis of the sex chromosomes in the heteromorphic bivalents of two X-7 translocations in male mice: R5 and R6

Electron microscopy of pachytene nuclei of mice heterozygous for either of two reciprocal X-7 translocations (R5 or R6) revealed a high frequency of heteromorphic bivalents involving the translocated chromosomes. In both translocations the break was in the proximal third of the 7 and the distal third of the X, but the R5 breaks were closer to the 7 centromere and X telomere than the R6 breaks. In both translocations the 7 frequently synapsed nonhomologously with the X7. In R5 the part of the X to which the 7 synapsed may include a region that synapses with the Y in normal mice. However, in R6 the 7 synapsed with a portion of the X that never synapses with the Y (Synapsis was clearl in the differentiated region). In both translocations the Y synapsed maximally with the X portion of the 7X in those nuclei in which there was nonhomologous synapsis of the 7 with the X7. The Y occasionally synapsed nonhomologously with the 7 portion of the 7X. The behavior of the bivalents suggests that the autosomal portions of the 7X and X7 may alter the behavior of the sex-chromosome portions. Both the nonhomologous synapsis of the Y with the 7X and the timing of events during pachytene have led us to question the homology between the X and Y in this species.     

Meiotic studies of translocations causing male sterility in the mouse. II. Double heterozygotes for Robertsonian translocations.

Unusual meiotic behavior of the XY chromosome pair was observed in sterile male mice doubly heterozygous for two Robertsonian translocations, Rb(16.17)7Bnr and Rb(8.17)1Iem. Nonrandom association between the X chromosome and the translocation configuration, ascertained from the frequencies of relevant C-band contacts, was found in 9 of 10 sterile males. Besides the nonrandom association, the XY chromosomes showed signs of impaired condensation, as judged by measurement of their lengths at diakinesis/MI of the first meiotic division. In contrast, neither nonrandom contact nor decondensation of the XY chromosomes pair was found in fertile males heterozygous for a single Robertsonian translocation, Rb1Iem or Rb7Bnr. The present observations lend indirect support to the working hypothesis advanced previously, the assumption that interference with X-chromosome inactivation is a possible cause of spermatogenic breakdown in carriers of various male-sterile chromosomal transloations. Alternative explanations of the available data, which cannot be ruled out, are briefly discussed.     

Robertsonian chromosomal variation and identification of metacentric chromosomes in feral mice

Cytogenetic studies of feral mice (M. musculus) from various but predominantly Alpine areas of Switzerland, carried out on random samples collected by spot-checks, established the widespread existence of metacentric chromosomes in the somatic karyotype. Despite the finding of the common occurrence of some of the metacentrics in different places, the examination of the possible homology or heterology by breeding procedures revealed the surprising fact that independence, partial or heterobrachial homology of the metacentric chromosomes prevail among mice from different geographical areas. Thus, the general picture is that of an array of different metacentric chromosomes derived from independent events of Robertsonian variation in the process of evolution. — While heterozygosity with independent metacentrics within a Robertsonian system may have a bearing on the fertility rate of a given mouse population, a more severe impairment of the reproductive capacity must be taken into account in mouse populations which possess different metacentrics with mono- or heterobrachial homologies. These conditions favour the assumption of the existence of a selective system of reproductive barriers further subdividing the species in many, more or less stable, micro-populations. — The chromosomal arms (telocentrics) involved in the formation of the metacentric chromosomes could be identified by Q- and G-banding techniques in combination with the results of crossbreeding, and were assigned to the corresponding telocentric autosomes of the mouse (Comm. Standard. Genet. Nomenclat. for Mice, 1972). Most of the telocentric autosomes of the mouse are included in one or more of the metacentrics found in the feral populations. By means of their isolation in separate lines, these metacentrics may be useful in experimental biology as marker chromosomes of defined identity carrying known linkage groups.     

Synaptonemal complex analysis of X-7 translocations in male mice: R2 and R6 quadrivalents

Synaptonemal complexes of surface-spread spermatocytes of mice heterozygous for reciprocal translocations R2 or R6 between the X-chromosome and chromosome 7 were examined by light and electron microscopy (EM). Measurements of the lengths of all chromosome axes involved in the translocation configurations and of the extent of synapsis were used to calculate the position of the break points of the two translocations. The breaks for R2 were determined to be at 62% of the 7 as measured from the centromere, and at 27% of the X. Quadrivalents were formed almost exclusively. The break points for R6 were calculated to be at 30% of the 7 as measured from the centromere, and at 75% of the X. Although in R6 the break in the X lies within the potential pairing region of the sex chromosomes, univalent Ys were rarely observed (6%). The EM sample of 76 nuclei contained: 42% quadrivalents, 52% heteromorphic bivalents, 4% trivalent plus Y univalent, and 2% X7-7 bivalent plus two univalents (7X and Y). Nonhomologous synapsis occurred in the quadrivalents of both R2 and R6. In R6 nonhomologous synapsis of the X portion of the 7X with the 7 involved up to 14% of the length of the 7. Methods are discussed for determining the position of the break points in the presence of nonhomologous synapsis. It is proposed that the high percentage of bivalents is due to premature desynapsis of the 7X from the 7 and that the X portion of the 7X axis confers its property of premature desynapsis on that portion of the 7 to which it is attached.     

Behavior of mice with robertsonian translocations of chromosomes

The behaviour of mice with normal karyotype and those with robertsonian translocations was studied. The ability of the animals to solve an extrapolatory task was analysed. The experimental procedure was initiated with presentation of a food bait which the animal could reach only through a small opening in a screen. As the mouse started drinking, the food cup was moved leftward or rightward disappearing from the animal's view. The problem was to move in the direction of food, in which case the mouse could find it behind one of two feeding holes, to the right or to the left of the starting point. Laboratory mice were not able to solve this problem, whereas mice containing Rb(8, 17)1 IEM in karyotype demonstrated the extrapolatory ability - they solve the task correctly in a significant majority of cases. By means of a series of backcrosses of Rb(8, 17)1 IEM carriers on CBA strain (these mice have no extrapolatory ability) and subsequent inbreeding, a novel inbred strain was obtained, coisogenic to CBA and possessing the robertsonian translocation Rb(8, 17)1 IEM. These mice with the CBA genetic background solve the extrapolatory problem successfully, the level of correct choices being significantly above the 50% chance level. At the same time, their performance was lower than that of outbred mice with Rb(8, 17)1 IEM, the phenomenon possibly being the result of the influence of CBA genetic background. Mice with Rb(8, 17)6 Sic were also shown to possess the extrapolatory ability.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dicentric and monocentric Robertsonian translocations in man

Summary 5 balanced Robertsonian translocations in man were identified by fluorescence studies. Orcein staining showed two distinct centromeres in 4 of these cases (tdic(13;13), tdic(13;14), tdic(15;21), tdic(21;22)) indicating breaks in the short arms of the involved chromosomes. The dicentric translocation chromosomes were rather stable but monocentrics were noticed in each case. Fluorescence- and measurement studies seemed to indicate that an invisible centromere and part of the short arms were present in these monocentric chromosomes. One case, t(14q21q), was monocentric in all metaphase plates but measurement studies were very suggestive of a visible 21 centromere and incorporation of the invisible 14 centromere (and short arm material) in the long arm of the translocated 14 chromosome, indicating that this translocation originally might have been a real dicentric. Heterochromatin staining was carried out in all cases. The tdic(15;21) showed 6 heterochromatin blocks; 2 of these blocks were probably satellites from chromosome No. 21, visible too in fluorescence. The 4 other translocations showed 4 separated blocks. No differences were observed between monocentrics and dicentrics supporting the theory of a preserved, but invisible centromere in monocentrics.

---

Zusammenfassung 5 balancierte humane Translokationen vom Robertson-Typ wurden durch Fluorescenzuntersuchungen identifiziert. Die Orceinfärbung zeigte in 4 dieser Fälle 2 distinkte Zentromere (tdic(13;13), tdic(13;14), tdic(15;21), tdic(21;22)). Dieser Fund ließ es als wahrscheinlich erscheinen, daß der Bruch am kurzen Arm der involvierten Chromosomen stattgefunden hatte. Die dizentrischen Translokationschromosomen waren verhältnismäßig stabil. Es wurden doch monozentrische Chromosomen in allen Fällen beobachtet. Eine Kombination von Fluorescenzuntersuchung und Messung der Chromosomen machte es wahrscheinlich, daß auch in diesen monozentrischen Chromosomen ein unsichtbares Zentromer und Teile der kurzen Arme vorhanden sind. Eine (14q21q)-Translokation hatte in allen Metaphasen nur ein Zentromer. Messungen jedoch deuteten an, daß das 21-Zentromer sichtbar war, daß aber das 14-Zentromer und Material der kurzen Arme am langen Arm des translozierten 14-Chromosoms inkorporiert waren. Das Translokationschromosom ist möglicherweise ursprünglich ein dizentrisches Chromosom gewesen. In allen Fällen wurde eine Heterochromatinfärbung ausgeführt. Die tdic(15;21) hatte 6 Heterochromatinblöcke. 2 davon waren wahrscheinlich die Satelliten des Chromosoms Nr. 21, die auch bei der Fluorescenzmikroskopie sichtbar waren. Die 4 anderen Translokationen hatten 4 separate Blöcke. Monozentrische und dizentrische Chromosomen zeigten hier keinen Unterschied, was die Theorie unterstützt, daß die Zentromere im monozentrischen Chromosomen erhalten, aber unsichtbar sind.

     

Robertsonian translocations and B chromosomes in the Wellington tree weta, Hemideina crassidens (Orthoptera: Anostostomatidae)

Two karyotypes within the species Hemideina crassidens are described, 2n = 15 (XO) and 2n = 19 (XO). These two karyotypes have a NF of 28. The 19-karyotype was found exclusively in the southern part of the species range and the 15-karyotype was found in the north. The differences between the two karyotypes are interpreted as arising from two Robertsonian translocations (fission/fusion). Laboratory matings between weta with the two karyotypes produced viable offspring. During meiosis in F1 intraspecific hybrids metacentric and acrocentric autosomes aligned to form two trivalents, confirming homologies predicted by Robertsonian translocations. The subspecies H. c. crassicruris, (confined to Stephens Island) was found to be polymorphic for a metacentric B chromosome. An unusual association of sex and presence of B chromosome was observed in this island population with Bs found only in male weta.     

Pachytene pairing and sperm counts in mice with single Robertsonian translocations and monobrachial compounds

Data on testis weights, sperm counts, and synaptonemal complexes are presented for mice carrying the following Robertsonian translocations: Rb(6.15)lAld; Rb(4.6)2Bnr; Rb(4.15)4Rma; Rb(6.15)lAld/Rb(4.6))2Bnr, which is male-sterile; and Rb(6.15)lAld/Rb(4.15)4Rma, which is male-fertile. In RblAld/Rb2Bnr sperm were absent or sparse, whereas the sperm count in RblAld/Rb4Rma was just over 50% of the parental value. The translocated chromosomes appeared as fully paired bivalents in homozygotes, as trivalents in single heterozygotes, and as quadrivalents in compounds. About 20-40% of trivalents had unsynapsed ends. The proportion of quadrivalents with unsynapsed ends was about 85% in the male-sterile compound, compared with 75% in the male-fertile compound. The proportion of quadrivalents associated with XY was about 70% in both. Testis weights, but not sperm counts, were found to differ in two of three reciprocal crosses. It is concluded that, in addition to pairing failure and autosome/XY association, the effect of translocations on spermatogenesis is affected by other factors, including genetic background, inbreeding, and perhaps environmental factors. It remains to be elucidated whether pairing failure and XY association are primary or secondary effects.     

Two new X-autosome Robertsonian translocations in the mouse

The influence of X-autosome Robertsonian (Rb) translocation hemizygosity on meiotic chromosome behaviour was investigated in male mice. Two male fertile translocations [Rb(X.2)2Ad and Rb(X.9)6H] and a male sterile translocation [Rb(X.12)7H] were used. In males of all three Rb translocation types, the acrocentric homologue of the autosome involved in the rearrangement regularly failed at pachytene to pair completely with its partner in the Rb metacentric. The centric end of the acrocentric autosome was found regularly to associate either with the proximal end of the Y chromosome or with the ends of nonhomologous autosomal bivalents; the proportions of cells with such configurations varied between pachytene substages and genotypes. Various other categories of synaptic anomaly, such as nonhomologous synapsis, foldback pairing and interlocks, affected the sex chromosome multivalent in a substantial proportion of cells. In one of the Rb(X.12)7H males screened, an unusual, highly aneuploid spermatocyte that contained trivalent and bivalent configurations was found. Rb translocation hemizygosity did not appear to increase to a significant extent the incidence of X-Y pairing failure at pachytene, although the incidence was elevated at metaphase I in Rb(X.12)7H animals. Overall, a comparison of the frequencies and types of chromosome pairing anomalies did not suggest that these were important factors in the aetiology of infertility in males carrying the Rb(X.12)7H translocation.     

Meiosis in trisomic female mice with Robertsonian translocations. I. Prophase pairing

The prophase oocytes of two murine Robertsonian translocation (Rb) trisomies of chromosomes 16 and 19 were investigated using electron microscopy and a whole-cell micro-spreading technique after silver staining. About 20% of fetuses of each type were trisomic. They were obtained by mating animals heterozygous for two Rb's, monobrachially homologous for either chromosome 16 or 19, to an entirely acrocentric stock. Because of the almost inevitable prenatal mortality of the trisomic embryos, their fetal ovaries were "rescued" by an in vitro method for prophase studies. Analysis of the recovered oocytes showed frequent, close pairing associations of the three trisomic axes and evidence suggesting that the closely apposed axes coincided with the side-by-side formation of parallel, complete, true synaptonemal complexes; hence, the cytogenetic dogma that pairing is always two-by-two was contradicted. The presence of two parallel complexes has implications for crossing-over recombination. Triple associations of axes were found in almost half the trisomy 19 (Ts19) and in about 70% of the trisomy 16 (Ts16) prophases. The extent of triple associations varied and was greater in Ts16 than in Ts19 oocytes. Other relevant observations concerned the proportions of univalents and of univalence of the trisomic axes (21% in Ts16 and 46% in Ts19) and the distinctive, thickened appearance of all univalent axes. The pairing behaviour observed in balanced heterozygotes confirms what appears to be nonhomologous pairing and synaptic adjustment within the short-arm axes of the Rb trivalents.