Analysis of synaptonemal complexes in two fertile heterozygous boars, both carriers of a reciprocal translocation involving an acrocentric chromosome

An electron microscopic study of synaptonemal complexes in two heterozygous fertile boars, one a carrier of a 4;14 reciprocal translocation and the second a carrier of this translocation associated with a 3;7 reciprocal translocation, is reported. The results showed heterologous pairing in almost all quadrivalents, as well as a lack of XY-quadrivalent association. This seemed to be a common feature of translocations in pigs, even if at least one acrocentric chromosome is involved, and may represent a significant meiotic mechanism that prevents spermatocyte loss, while the production of genetically unbalanced gametes leads to loss of progeny through abortion.     

XY pair associates with the synaptonemal complex of autosomal male-sterile translocations in pachytene spermatocytes of the mouse (Mus musculus)

Analysis of the chromosome behaviour at pachytene has been performed by means of the silver staining technique visualizing the synaptonemal complexes (SCs) in male mice heterozygous for the male-sterile translocations T(5;12)31H, T(16;17)43H and T(7;19)145H, respectively. The T(9;17)138Ca male heterozygotes and T43H/T43H homozygous males were used as fertile controls. The sterile mice displayed a high frequency (about 60%) of pachytene spermatocytes with autosomal translocation configuration located in close vicinity of the XY pair. The dense round body (XAB), normally located near the X-chromosome axis in fertile males, exhibited abnormal affinity to translocation configuration in the sterile translocation heterozygotes. The incomplete synapsis of autosomes involved in translocation configuration was observed in more than 70% of the pachytene spermatocytes with the male-sterile translocations but in less than 20% of the cells from T138Ca fertile male.s. A hypothesis relating the spermatogenic arrest of carriers of male-sterile rearrangements to the presumed interference with X chromosome inactivation in male meiosis is discussed.     

A Somatic Origin of Homologous Robertsonian Translocations and Isochromosomes

One t(14q14q), three t(15q15q), two t(21q21q), and two t(22q22q) nonmosaic, apparently balanced, de novo Robertsonian translocation cases were investigated with polymorphic markers to establish the origin of the translocated chromosomes. Four cases had results indicative of an isochromosome: one t(14q14q) case with mild mental retardation and maternal uniparental disomy (UPD) for chromosome 14, one t(15q15q) case with the Prader-Willi syndrome and UPD(15), a phenotypically normal carrier of t(22q22q) with maternal UPD(22), and a phenotypically normal t(21q21q) case of paternal UPD(21). All UPD cases showed complete homozygosity throughout the involved chromosome, which is supportive of a postmeiotic origin. In the remaining four cases, maternal and paternal inheritance of the involved chromosome was found, which unambiguously implies a somatic origin. One t(15q15q) female had a child with a ring chromosome 15, which was also of probable postmeiotic origin as recombination between grandparental haplotypes had occurred prior to ring formation. UPD might be expected to result from de novo Robertsonian translocations of meiotic origin; however, all de novo homologous translocation cases, so far reported, with UPD of chromosomes 14, 15, 21, or 22 have been isochromosomes. These data provide the first direct evidence that nonmosaic Robertsonian translocations, as well as isochromosomes, are commonly the result of a mitotic exchange.     

Mating between two balanced translocation carriers in two unrelated families

Partial trisomy 9p and a 13/14 translocation occurred in the daughter of a t(5;9)(p15;p12) mother and a t(13;14)(p11;q11) father. Two additional offspring displayed a normal karyotype and a translocation trisomy 13 respectively. Two first cousins, selected for chromosome analysis because of a spontaneous abortion, were found to have an identical translocation t(14;21)(p11;q11). Their second pregnancy was monitored by midtrimester amniocentesis and disclosed a balanced fetus. The different zygotic chromosome constitutions and the counselling problems in the marriages between two balanced translocation carriers are discussed.     

^14CO2 Fixation and Translocation of Photoassimilates as Selection Criteria of Egyptian Taro Genotypes

The growth characterlstlcs, different physlological parameters, photosynthetic activity （^14CO2 fixation）, and the translocatlon rate of photoassimllates In different taro （Colocasia esculenta L. Schott） genotypes was studled In order to determlne the posslble use of these parameters as selectlon crlterla for dlfferent wldely used genotypes of taro （Delta No. 9, 15, 20, 21, and balady）. The results obtalned suggest that Delta No. 21 shows the most slgnlflcant increase In all parameters tested compared wlth the control （balady）, followed by Delta No. 9, 15, and 20, respectively. The results show a positive correlation between photosynthetlc actlvlty, translocatlon efflclency, and total yield. The selected clone Delta No. 21 Is recommended for cultlvatlon In the delta reglon of Egypt.     

Aberrations of the synaptonemal complexes in a male 46,XY,-14,+der(14)t(Y;14)

An unbalanced translocation 46,XY,-14,+der(14)t(Y;14)(q11;p11) was observed in an azoospermic male, with reduced spermatogenesis and absent spermiogenesis. At the pachytene stage of spermatocyte 1, the segments of the 2 Y chromosomes, fluorescent with quinacrine mustard, were always found close together. This proximity was also demonstrated by the study of synaptonemal complexes, which showed, in addition, an unusual hypercondensation of the proximal segment of bivalent 14, adjacent to the translocated Y chromosome. This allows us to propose that this hypercondensation might correspond to an inactivation of the translocated autosome, which could be responsible of the degeneration of the germ cells.     

Meiotic analysis of two human reciprocal X-autosome translocations

Two cases of human reciprocal X-autosome translocation, t(X;12) and t(X;2), are described in sterile males, along with meiotic findings. Each carrier had inherited the translocation from his mother. Both showed azoospermia and germ-cell maturation arrest at the primary spermatocyte level, with most cells being arrested at the pachytene stage. A few metaphase I (MI) divisions were found, with occasional metaphase II cells being seen in the t(X;2) carrier. MI air-dried preparations gave clear evidence of chain quadrivalent formation. In the t(X;2) heterozygote, the pairing characteristics of the quadrivalent at pachytene were also analyzed in electron microscopic spreads. Disturbance of pairing around the breakpoints characterized most quadrivalents, and there was evidence in about 20% of the cells that nonhomologous pairing had taken place between the translocated chromosomes and the normal chromosome 2. Comparisons are made with similar nonhomologous pairing configurations seen at pachytene in quadrivalents of male reciprocal X-autosome translocations of the mouse.     

Chromosome analysis of spermatozoa from a male heterozygous for a 13;14 Robertsonian translocation

Summary Cytogenetic analysis of 78 spermatozoa from a man heterozygous for a t(13;14) Robertsonian translocation was performed. R banding was applied for chromosomal identification. Incidence of normal and balanced complements were respectively 50% and 41.3%. Six unbalanced complements (7.7%) were observed, resulting from adjacent segregation. Although alternate segregation is the most common mode of distribution, the possibility of producing unbalanced zygotes exists. The frequency of abnormalities unrelated to the translocation was 16.5% including 12.8% hypohaploïdy, 2.5% hyperhaploidy, and 1.2% of structural aberrations. An excess of t(13;14) X complements was observed (24 with X versus 14 with Y). This may result from the close association between trivalent (13;14) and X chromosome observed in the pachytene spermatocyte nucleus.     

Is there an interchromosomal effect in reciprocal translocation carriers? Sperm FISH studies

Chromosome translocations have been known to affect disjunction of chromosomes unrelated to the translocation in the mouse and in Drosophila. However, in humans, an interchromosomal effect in chromosome translocations has not been demonstrated. The availability of techniques that allow the study of nondisjunction in sperm cells has permitted us to evaluate the possibility of an interchromosomal effect in male translocation heterozygotes. In this study, multicolor fluorescence in situ hybridization was used to determine levels of disomy for the clinically relevant chromosomes X, Y, 13, 18, and 21 in 332,858 spermatozoa from nine reciprocal translocation heterozygotes and nine controls with normal karyotypes. The specific translocations studied were as follows: t(10;12)(p26.1;p13.3), t(2;18)(p21;q11.2), t(3;19)(p25;q12), t(5;8)(q33;q13), t(11;22)(q23;q11), t(3;4)(p25;p16), t(8;9) (q24.2;q32), t(10;18)(q24.1;p11.2), and t(4;10)(q33;p12.2). Comparisons of disomy rates between carriers and controls were performed by using the Mann-Whitney test. Our results showed that the rates of sex chromosome hyperhaploidy were similar in controls (0.21%) and in translocation carriers (0.19%). Similarly, the frequencies of disomy for chromosomes 13, 18, and 21 did not differ significantly between controls and carriers (0.05% versus 0.08%, 0.07% versus 0.03%, and 0.14% versus 0.20%, respectively). Sex chromosome nondisjunction was more common than nondisjunction of chromosomes 13 and 18 both in controls (P=0.0057) and in carriers (P=0.0008). Similarly, the rates of chromosome disomy for chromosome 21 were higher than those for chromosomes 13 and 18 in both controls (P=0.0031) and translocation carriers (P=0.0057). In our study, the excess of chromosome 21 disomy versus disomy of the other autosomes was more pronounced in carriers than in controls. Thus, although the difference of disomy 21 between controls and carriers was not statistically significant, it is worthy of attention.     

Molecular cytogenetic analysis of follicular lymphoma (FL) provides detailed characterization of chromosomal instability associated with the t(14;18)(q32;q21) positive and negative subsets and histologic progression

We analyzed a cohort of 61 follicular lymphomas (FL) with an abnormal G-banded karyotype by spectral karyotyping (SKY) to better define the chromosome instability associated with the t(14;18)(q32;q21) positive and negative subsets of FL and histologic grade. In more than 70% of the patients, SKY provided additional cytogenetic information and up to 40% of the structural abnormalities were revised. The six most frequent breakpoints in both SKY and G-banding analyses were 14q32, 18q21, 3q27, 1q11-q21, 6q11-q15 and 1p36 (15-77%). SKY detected nine additional sites (1p11-p13, 2p11-p13, 6q21, 8q24, 6q21, 9p13, 10q22-q24, 12q11-q13 and 17q11-q21) at an incidence of >10%. In addition to the known recurring translocations, t(14;18)(q32;q21) [70%], t(3;14)(q27;q32) [10%], t(1;14)(q21;q32) [5%] and t(8;14)(q24;q32) [2%] and their variants, 125 non-IG gene translocations were identified of which four were recurrent within this series. In contrast to G-banding analysis, SKY revealed a greater degree of karyotypic instability in the t(14;18) (q32;q21) negative subset compared to the t(14;18)(q32;q21) positive subset. Translocations of 3q27 and gains of chromosome 1 were significantly more frequent in the former subset. SKY also allowed a better definition of chromosomal imbalances, thus 37% of the deletions detected by G-banding were shown to be unbalanced translocations leading to gain of genetic material. The majority of recurring (>10%) imbalances were detected at a greater (2-3 fold) incidence by SKY and several regions were narrowed down, notably at gain 2p13-p21, 2q11-q21, 2q31-q37, 12q12-q15, 17q21-q25 and 18q21. Chromosomal abnormalities among the different histologic grades were consistent with an evolution from low to high grade disease and breaks at 6q11-q15 and 8q24 and gain of 7/7q and 8/8q associated significantly with histologic progression. This study also indicates that in addition to gains and losses, non-IG gene translocations involving 1p11-p13, 1p36, 1q11-q21, 8q24, 9p13, and 17q11-q21 play an important role in the histologic progression of FL with t(14;18)(q32;q21) and t(3q27).     

Cytogenetic analysis of 400 sperm from three translocation heterozygotes

Summary Sperm chromosome complements were studied in three men who carried reciprocal translocations. A total of 400 sperm were karyotyped after in vitro penetration of hamster eggs: 217 sperm from t(2;9) (q21;p22), 164 from t(4;6) (q28;p23) and 19 from t(7;14) (q21;q13). All possible 22 and 31 meiotic segregations were observed for t(2;9) and t(4;6); for t(7;14) only 22 segregations were observed. For alternate segregations, the number of normal sperm was not significantly different from the number of sperm carrying a balanced form of the translocation in any of the translocations, as theoretically expected. The percentage of sperm with an unbalanced form of the translocation was 57% for t(2;9), 54% for t(4;6) and 47% for t(7;14). There was no evidence for an interchromosomal effect in any of the translocations since the frequencies of numerical abnormalities (unrelated to the translocation) were within the normal range of control donors. The frequencies of X- and Y-bearing sperm did not differ significantly from 50%. Results from a total of 17 reciprocal translocations studied by sperm chromosomal analysis were reviewed.     

Translocation Down syndrome in Ohio 1970-1981: epidemiologic and cytogenetic factors and mutation rate estimates.

Sixteen hundred eighty-eight Down syndrome live births, including 65 (5.2%) translocations, were ascertained in Ohio between 1970 and 1981. Translocations of known origin were 24.4% maternal, 2.2% paternal, and 73.3% de novo. Translocation subtypes were 14/21 (45.7%), 15/21 (2.9%), 21/21 (40.0%), 21/22 (2.9%), and other (8.5%). Among 14/21 translocations, 33.3% were maternal in origin and 66.7% were de novo, while 100% of 21/21 translocations were de novo. No differences were found when the maternal- and paternal-age distributions of all translocations or various translocation subsets were compared with the live-birth control distributions. However, mean maternal and paternal ages of de novo translocations were significantly lower than that of the live-birth controls. Ohio data showed the average maternal age of de novo D/21 cases to be significantly lower than the control. Ages of both parents of de novo G/21 cases and paternal age of D/21 cases were not different from the control. De novo translocation mutation rate estimates were 0.8 X 10(-5) for 14/21, 1.2 X 10(-5) for 21/21, and 2.2 X 10(-5) overall. Ohio estimates (3.2 X 10(-5) for 1970-1972 and 1.4 X 10(-5) for 1973-1975) did not reflect the increase in mutation rate previously found in New York during 1973-1977.     

Meiotic products of two reciprocal translocations studied by multicolor fluorescence in situ hybridization

The sperm products of two male carriers of reciprocal translocations were studied by fluorescence in situ hybridization (FISH) using a combination of three probes for each translocation. One patient carried a t(2;18)(p21;q11.2), the other a t(8;9)(q24.2;q32). The probes selected included a centromeric marker for each chromosome involved in the translocation plus a third probe distal to the translocation breakpoint of one of the translocation chromosomes. This assay identifies alternate, adjacent 1, adjacent 2, and 3:1 types of meiotic products. It allows the identification of recombination events and also estimation of the frequency of diploidy. For the t(2;18), the frequency of normal and balanced sperm and of adjacent 1, adjacent 2, and 3:1 products was 43.6%, 29. 8%, 10.5%, and 12.8%, respectively. Similar segregation patterns had been reported for this donor by direct sperm karyotyping of sperm cells. For the t(8;9), the frequency of normal and balanced sperm and of adjacent 1, adjacent 2, and 3:1 products was 44.4%, 41%, 3.1%, and 9.4%, respectively. The frequency of complementary adjacent 1 products was statistically different in both the t(2;18) (P < 0. 0001) and the t(8;9) (P < 0.0001) carrier. When the number of adjacent 2 products with one translocation chromosome (regardless of normal or derivative) was compared to the number of adjacent 2 products with the second translocation chromosome (again, regardless of normal or derivative), no statistical difference was noted for either the t(2;18) (P = 0.32) or the t(8;9) (P = 0.69). Recombination events within the interstitial segment of chromosome 2 were statistically higher than those seen in chromosome 18 (P < 0. 0001), whereas in chromosomes 8 and 9, recombination in the interstitial segments was similar (P = 0.64). The rate of diploidy was similar in both the t(2;18) (0.5%) and the t(8;9) (0.6%). Thus, FISH provides chromosome information on the sperm products produced by translocation carriers, although it cannot provide an assessment of the full chromosome complement of the spermatozoon.     

The cellular homologue of the transforming gene of SKV avian retrovirus maps to human chromosome region 1q22----q24

We report the chromosomal localization of the cellular oncogene SKI, the putative oncogene of the Sloan-Kettering viruses (SKVs), a group of transforming retroviruses that had been isolated from chicken embryo cells infected with the avian leukosis virus tdB77. Southern blot analysis of DNA from mouse X human somatic cell hybrids with the v-SKI probe established synteny with chromosome 1, but excluding the region 1pter----q21. In situ hybridization of the same probe both to human spermatocyte pachytene and lymphocyte metaphase chromosomes enabled precise localization of the gene to the region 1q22----q24, a region that frequently is involved in translocations and other rearrangements in diverse human tumor types. In situ hybridization studies of metaphase spreads from a small noncleaved cell lymphoma that exhibited a t(1;14)(q21;q32) translocation showed that SKI translocates to the der(14) chromosome. Cytogenetic analysis of 65 prospectively ascertained non-Hodgkin's lymphomas revealed that the SKI region undergoes nonrandom breakage leading to translocations. Further analysis of the chromosome breaks in this group of lymphomas suggested that those involving the SKI site probably are of importance in tumor progression.     

Synaptonemal complexes in a subfertile man with a pericentric inversion in chromosome 21. Heterosynapsis without previous homosynapsis

Analysis of surface-spread synaptonemal complexes of zygotene and pachytene spermatocytes was carried out on a human male carrier of a pericentric inversion of chromosome 21 ascertained after four miscarriages. The synaptic behavior of the bivalent, which could be unambiguously identified by its nonaligned kinetochores, was analyzed. All zygotene and pachytene spermatocytes had 22 linearly paired autosomal bivalents, with apparently normal synaptonemal complexes, and no evidence of a loop configuration in the 50 cells analyzed. According to the XY type (classification of Solari), the cells were distributed across zygotene and pachytene stages, not exclusively in the late pachytene to which adjustment is conventionally thought to be confined. It is suggested that inverted segments heterosynapse at early pachytene, without previous homosynapsis. It is expected that this meiotic process leads to failure of crossing-over, reduces the production of unbalanced gametes, and the risk of recombinant offspring, but can increase the incidence of aneuploidy as a result of nondisjunction during meiosis I (a frequent cause of pregnancy wastage).     

The complex translocation (9;14;14) involving IGH and CEBPE genes suggests a new subgroup in B-lineage acute lymphoblastic leukemia

Many subtypes of acute lymphoblastic leukemia (ALL) are associated with specific chromosomal rearrangements. The complex translocation t(9;14;14), a variant of the translocation (14;14)(q11;q32), is a rare but recurrent chromosomal abnormality involving the immunoglobulin heavy-chain (IGH) and CCAAT enhancer-binding protein (CEBPE) genes in B-lineage ALL (B-ALL) and may represent a new B-ALL subgroup. We report here the case of a 5-year-old girl with B-ALL, positive for CD19, CD38 and HLA-DR. A direct technique and G-banding were used for chromosomal analysis and fluorescentin situ hybridization (FISH) with BAC probes was used to investigate a possible rearrangement of the IGH andCEBPE genes. The karyotype exhibit the chromosomal aberration 46,XX,del(9)(p21),t(14;14)(q11;q32). FISH with dual-color break-apartIGH-specific and CEPBE-specific bacterial artificial chromosome (BAC) probes showed a complex t(9;14;14) associated with a deletion of cyclin-dependent kinase inhibitor 2A (CDKN2A) and paired box gene 5 (PAX5) at 9p21-13 and duplication of the fusion gene IGH-CEBPE.     

Molecular cytogenetic characterization of a familial balanced reciprocal translocation t(11;18) (q13.3; q23) associated with pregnancy wastage

A new male patient associated with a pregnancy wastage was detected in China. Cytogenetic analyses including G-banding, chromosome painting and observation of synaptonemal complexes (SCs) demonstrated that the pregnancy wastage was associated with a balanced reciprocal translocation t(11;18) (q13.3; q23). The proband was the carrier of the translocation and his karyotype was 46,XY,t(11;18)(11pter-->11q13.3:: 18q23-->18qter; 18pter-->18q23::11q13.3-->11qter). The pedigree was analyzed based on a G-banded karyotype of the nine familial members. The translocation chromosomes came from the proband's mother. The result of the SC observation in the proband showed that each of the spermatocytes displayed one quadrivalent during their pachytene stages. In the quadrivalents, there existed homologous and nonhomologous synapses and the latter occurred widely during early, middle and late pachytene stages. The reasons and genetic basis of the pregnancy wastage are discussed.     

Spermatozoa karyotyping and meiotic segregation: a study of 4 reciprocal translocations

Sperm cytogenetics was carried out using technique of in vitro heterospecific human-hamster fertilization. Sperm of 4 men heterozygous from 4 reciprocal translocations (t(4; 17), t(5; 13), t(6; 7) and t(9; 18] was studied. Segregations were various but a majority of unbalanced complements resulting from adjacent 1 segregations was observed. This prevalence was stronger when the pachytene diagram predisposed the translocation to this mode of imbalance at term.     

Interchange trisomy 21 by t(1;21)(p22;q22)mat

Interchange trisomy 21 by t(1:21)(p22:q22)mat: Interchange trisomy 21 by t(1;21)(p22;q22)mat was identified in a sporadic patient with Down syndrome. With a 21q22 specific probe, we observed signals on both normal 21 chromosomes and on the der. We reviewed the 23 published reports of families with reciprocal translocations leading to viable offspring with interchange trisomy 21. The breakpoints in chromosome 21 were mainly located in 21q (19/24 instances, including the present report) and in 19/23 cases the other chromosome involved in the translocation was (pairs 1-12). The underlying 3:1 segregation occurred mainly in carrier mothers; only one patient presented a de novo imbalance and in another case the father was the carrier. In addition, there were 4 instances of concurrence with another unbalanced segregation (adjacent-1 or tertiary trisomy) and 3 families with recurrence of interchange trisomy 21. The mean age of 14 female carriers at birth of interchange trisomy 21 offspring (24.8 yr) was lower that the mean (28.3 yr) found in a larger sample of mothers of unbalanced offspring due to 3:1 segregation (mostly tertiary trisomics) and was not increased with respect to the general population average. Overall, these data agree with previous estimates regarding recurrence risk (9-15%) and abortion rate (about 28%) in female carriers ascertained through an interchange trisomic 21 child.     

Banding studies and synaptonemal complex analysis of an X-autosome translocation in the domestic pig

In a litter of nine domestic pigs, a translocation between the X-chromosome and chromosome 13 was found in six individuals: four males and two females. The translocation was presumed to have originated in the dam. Banding studies indicated that the breaks preceding the translocation had occurred in a distal GTG-negative band of the long arm of the X, 15-30% of the length of Xq from the telomere, and proximally in chromosome 13, 15-25% from the centromere. The normal X of the females invariably replicated its DNA late. Synaptonemal complex analysis of spermatocytes demonstrated a quadrivalent in 75 of 85 analyzable cells (88.2%), and in 10 cells (11.8%) one trivalent and one univalent were found. Extensive nonhomologous pairings were visualized in the pachytene stage by applying an 'overlap' test measuring the sex chromosomes and collating their pairings. An arrest in male meiosis was verified histologically; no meiotic stages later than pachytene developed. This resulted in sterility, with considerable testicular hypoplasia. The records of female fertility were available only for the dam and did not show any deviations from the average of the herd.