Embryonic loss in superovulated cattle caused by the 1;29 Robertsonian translocation

The effect of the 1;29 Robertsonian translocation on fertility was studied using embryos resulting from matings of nine carrier cows and two carrier bulls. Embryos were collected from the following three mating groups utilizing superovulation: normal bull cross normal cow, normal bull cross translocation carrier cow, and translocation carrier bull cross normal cow. The proportion of ova which were fertilized did not vary among the groups, indicating that fertilization rates were not affected by the translocation. The translocation cows did yield fewer embryos on average than did cows with normal karyotypes, which may suggest ovulation rates are reduced (at least after superovulation attempts) in cattle carrying the 1;29 translocation. Twenty of 39 embryos successfully karyotyped had abnormal chromosome complements. All four of the theoretically predicted karyotypes and two additional abnormal combinations were found. Eight of 39 (20.5%) embryos karyotyped had unbalanced karyotypes which would have resulted in embryonic loss. The proportion of embryos with unbalanced karyotypes, was slightly higher when the cow (36%) carried the translocation than when the bull (19%) did. Results of this study indicate that fertility is impaired due to the presence of this translocation. The major loss in reproductive potential appears to be due to embryonic loss rather than fertilization failure.     

Fertility effects of the 14;20 Robertsonian translocation in cattle

Superovulation and embryo collection procedures were used to study the effect of the 14;20 Robertsonian translocation on fertility and embryo viability. Karyotypes were successfully completed on cells from 77 of the 279 embryos prepared for such analysis. Embryos from 4 cows heterozygous for the translocation were studied. Two bulls with the same condition were studied by using their semen in artificial insemination of cows with normal karyotypes. The proportions of fertilized ova and transferable embryos were not different between cows with the 14;20 translocation and those with normal karyotypes, indicating that fertilization rates were not affected by the translocation. Twenty-two percent of the embryos which were karyotyped had an unbalanced karyotype and would theoretically not have survived to term. All of the theoretically predicted chromosome complements from such a translocation were observed as were three 58,XX,t karyotypes and a 58,XX karyotype. There was no difference in the percentage of embryos with abnormal karyotypes whether the cow or bull was the carrier. Results therefore indicate that fertility is rather severely impaired in carriers of the 14;20 translocation, as was observed with the 1;29 translocation, with most loss due to embryo mortality rather than a lowered conception rate.     

Detection of an unbalanced translocation (4;14) in a mildly retarded father and son by flow cytometry

Summary A child with impaired intelligence, minor dysmorphisms, obesity and genital hypoplasia was found to have an apparently balanced translocation, 46,XY,t(4;14)(q12;q13), following cytogenetic analysis. The same rearrangement was also detected in the child's father, who had similar phenotypic abnormalities to his son. Detailed study of flow karyotypes produced from lymphoblastoid cell lines established that in both patients the translocation was in fact unbalanced with approximately 11 million base pairs of DNA (corresponding to about 6.0% of chromosome 4 or 11.0% of chromosome 14) being lost.     

The 11q;22q translocation: A European collaborative analysis of 43 cases

Summary Translocation between the long arms of chromosomes 11 and 22 is usually detected in offspring with an unbalanced karyotype following a 3:1 disjunction resulting in partial trisomy. Since by the end of 1976 it was suspected that this translocation might be more frequent than one would deduce from published reports, it was decided to call for a collaborative effort in Europe to collect unpublished cases. In response, 42 cases were collected in Europe, and one case from New Zealand was added. The following countries were represented with the number of cases indicated in parentheses: Czechoslovakia (2), Denmark (4), Finland (3), France (6), Germany (1), Italy (5), The Netherlands (9), Sweden (6), United Kingdom (4), Yugoslavia (2). The wide geographical distribution indicates a multifocal origin of the translocation. Among the unpublished cases, 31 were ascertained as unbalanced carriers [47,XX or XY,+der(22),t(11;22)] and 12 as balanced balanced carriers [46,XX and XY,t(11;22)]. Among the published cases, 10 were ascertained in unbalanced and 3 in balanced carriers. The breakpoints of the translocations indicated by the contributors varied, the most frequently reported being 11q23;22q11 (25 cases), followed by q25;q13 (10 cases). While the first one seems more likely, it was not possible to decide whether the breakpoints were the same in all cases.All 32 probands with unbalanced karyotypes had inherited the translocation, 31 from the mother and only 1 from the father. This ratio became 43:1 when the published cases were added. A segregation analysis revealed that in families ascertained through probands with unbalanced karyotypes there was a ratio of carriers to normal (all karyotyped) 54:55, not a significant difference. The formal maximum (minimum) recurrence risk for this unbalanced translocation was calculated to be 5.6% (2.7%). When the ascertainment was through a balanced proband, the maximum risk was 2.7%. The risk was calculated as 5.7% for female and 4.3% for male carriers. The mean family size was 1.67 for the offspring of female carriers and 0.78 for the offspring of male carriers. This significant difference suggests that heterozygosity for the translocation reduces fertility in males. Indeed, several of the probands with balanced karyotypes were ascertained because of sub- or infertility. Only 2 de novo translocations were found among the 59 probands, and both, were among the 12 cases ascertained as balanced carriers. The source, quality, and quantity of the clinical data for the subjects with unbalanced karyotypes were variable, and no definite conclusions were possible about phenotypes. The following signs were recorded in 10 or more of the 45 cases: low birth weight, delayed psychomotor development, hypotonia, microcephaly, craniofacial asymmetry, malformed ears with pits and tags, cleft palate, micro-/retrognathia, large beaked nose, strabismus, congenital heart disease, cryptorchidism, and congenital dislocation of the hip joints. Many signs were similar to those considered typical of trisomy 11q, and the phenotype coincided almost completely with the presumptive phenotype of complete trisomy 22. No cases with coloboma was recorded, while other signs of the cat-eye syndrome were found in several probands. This might indicate that individuals with the cat-eye syndrome and carriers of the unbalanced 11/22 translocation have the same segment of 22 in triplicate plus or minus another chromosome segment.     

Segregation and fertility analysis in an autosomal reciprocal translocation, t(1;8)(q41;q23.1).

We report a previously undescribed autosomal reciprocal translocation, t(1;8)(q41;q23.1). It segregates in three families whose common origin lies at least 11 generations back. No examples of unbalanced karyotypes were encountered. Moreover, there was no circumstantial evidence that such live births had occurred during earlier generations. Couples in which one spouse was a translocation carrier were compared to related couples with normal karyotypes. The 15 carrier families had significantly more spontaneous abortions (32%) than the 22 normal couples (10%), irrespective of the sex of the carrier parent. However, the mean number of children was equal in both groups (2.0 and 2.4). Carrier families produced 17 children with a balanced translocation and seven with a normal karyotype. This deviates significantly (P = .04) from the expected 1:1 ratio. We conclude that this malsegregation helps to maintain the translocation in the population. These results show that empirically derived 1:1 segregation ratios previously reported in series that combine many different translocations do not apply to all individual translocations.     

Different risks in two familial translocations t(9;12) with similar breakpoints.

The risk of offspring with unbalanced karyotypes born to carriers of reciprocal chromosomal translocation (RCT) is important to evaluate for further family planning and prenatal diagnosis. The authors describe two families with carriers of similar RCT concerning breakpoint positions and discuss the different individual risks for abnormal progeny. These translocations were studied by GTG, RBG and CBG banding. They have the same breakpoint on 9p, i.e. 9p22, and a different one on 12p, i.e. terminal (pter----p13) and intermediate (p11.2), respectively. The risk value of 27% for family 1 was obtained directly from the large enough pedigree (high risk) a risk value of about 5% was estimated for family 2, according to the guidelines of Stene and Stengel-Rutkowski (1988). The data show that similar translocations with only slight differences in the breakpoints position have different risks for unbalanced progeny. Results of these empiric findings may be used directly in genetic counselling of a family with RCT leading to a single imbalance of the same segment.     

A family with a high risk of segregation for an autosomal unbalanced reciprocal translocation

Summary A family with autosomal reciprocal translocation t(4;13) (q25;q31) with a sibship comprising 2 children with unbalanced karyotypes, der(13) partial trisomy 4q, 1 child with the balanced translocation, and 2 abortions were studied. The segregation risk of unbalanced derivation in reciprocal translocations is discussed. The clinical picture of the 2 children with partial trisomy 4q is compared with similar cases.     

Use of semen from a bull heterozygous for the 1 29 translocation in an IVF program

In cattle, a translocation of the Robertsonian type between the largest and smallest chromosome leads to a reduction in fertility. This is substantiated by reduced nonreturn rates in daughter groups of bulls carrying the 1 29 translocation and in the heterozygous bulls themselves. This reduction in fertility is thought to be due to the early death of embryos with unbalanced karyotypes. The influence of semen from a bull known to be heterozygous for the 1 29 translocation on the outcome of a bovine IVF program was investigated. There was a significant difference (P<0.005) in terms of cleavage rate (59.8 vs 71.1%) and blastocyst rate (12.0 vs 20.0%) between the carrier and control bull, respectively. There was no difference in blastocyst quality as measured by cell number. The results observed in vitro are consistent with the field fertility records of the 2 bulls in terms of nonreturn rates (59.2 vs 70.6%, for the carrier and control bull, respectively).     

Unbalanced reciprocal translocations in cases of Prader-Willi syndrome

Summary A case of Prader-Willi syndrome (PWS) associated with a de novo unbalanced 15q;17q reciprocal translocation presumptively resulting from the tertiary monosomic form of 3:1 meiotic disjunction is described. Twenty-three similar unbalanced translocations have been identified from the literature. The 24 karyotypes are characterised by having 45 chromosomes, monosomy for the pericentromeric region of chromosome 15 (range pter»q11 to q21), and little monosomy of the recipient (non-15) chromosome. Two-thirds of the cases with these karyotypes have phenotypic features of PWS. It seems probable that (i) where unbalanced reciprocal translocations are associated with PWS, they will almost invariably be presumptive segregants of the tertiary monosomic form of 3:1 disjunction and (ii) the majority of cases found with this type of karyotype, particularly it appears when de novo in origin, will be associated with phenotypic features of PWS.     

Partial duplication 5q syndrome: phenotypic similarity in two sisters with identical karyotype (partial duplication 5q33 leads to 5qter and partial deficiency 8p23 leads to pter).

Two sisters with statomotor developmental retardation microcephaly, hydrocephalus internus and externus without signs of pressure, heart defect (ventricular septal defect), early pulmonary resistance and characteristic facial changes were found to have the same unbalanced karyotype with partial trisomy 5q3300 leads to 5qter and partial monosomy 8p2300 leads to 8pter, derived from a balanced reciprocal paternal translocation: 46,XY,t(5;8)(q3300;p2300). The older girl was tested for the erythrocyte enzyme glutathion reductase. She had normal values.     

Robertsonian Translocations: An Overview of 872 Robertsonian Translocations Identified in a Diagnostic Laboratory in China

Robertsonian translocations (ROBs) have an estimated incidence rate of 1/1000 births, making this type of rearrangement the most common structural chromosomal abnormalities seen in the general population. In this study, we reports 872 cases of ROBs from 205,001 specimens karyotyped postnatally in a single accredited laboratory in China, including 583 balanced ROBs, 264 unbalanced ROBs, 9 mosaic ROBs, and 18 complex ROBs. Ninety-three percent of the balanced ROBs observed were adults with infertility, miscarriage, or offspring(s) with known chromosomal abnormalities. Significant excess of females were found to be carriers of balanced ROBs with an adjusted male/female ratio of 0.77. Ninety-eight percent of the unbalanced ROBs observed were children with variable referral reasons. Almost all of the unbalanced ROBs involved chromosome 21 except a single ROB with [46,XX,der(13;14),+13] identified in a newborn girl with multiple congenital anomalies. Multiple novel ROB karyotypes were reported in this report. This study represents the largest collections of ROBs in Chinese population.     

Selective elimination of chromosomally unbalanced zygotes at the two-cell stage in the Chinese hamster

The gametic and zygotic selection of genome imbalance was investigated in the Chinese hamster by direct chromosome analyses of spermatocytes and preimplantation embryos from crosses between chromosomally normal females and males heterozygous for a reciprocal translocation, T(2;10)3Idr, abbreviated here as T3. The karyotypes and the frequencies of embryos observed at the first cleavage in the cross +/+female X T3/+male were consistent with those expected from MII scoring in male T3 heterozygotes. Therefore, it was concluded that there was neither gametic selection against genome imbalance nor zygotic selection from fertilization until the first cleavage metaphase. However, 9.1-10.8% of embryos were arrested at the two-cell stage, and karyotypes of these embryos were confirmed as 22(2,10,10,10(2)), 21(2,10,10), and 21(2,10,10(2)). The common abnormality of these embryos was partial monosomy of chromosome 2. Among day 4 embryos, some chromosomally unbalanced embryos, mainly with a deficiency of other segments of chromosomes 2 and 10, had fewer blastomeres than chromosomally balanced embryos. This finding suggests that cleavage of these embryos had been retarded by day 4 of gestation.     

Autosomal dominant congenital cataract and microphthalmia associated with a familial t(2;16) translocation

Summary We describe a family in which autosomal dominant congenital cataract and microphthalmia were segregating together with a reciprocal translocation t(2; 16) (p22.3;p13.3) through three generations. This family included four individuals with balanced translocations, three with partial trisomy 2p derived from this translocation, and two with a normal karyotype. All of the subjects with balanced and unbalanced translocations had congenital cataract and microphthalmia, whereas the two individuals with normal karyotypes did not show any ocular anomalies. These observations suggest that the altered function of a gene that lies on the 16p13.3 band and that has an important role in the development of the eye is responsible for this disorder.     

The establishment and application of preimplantation genetic haplotyping in embryo diagnosis for reciprocal and Robertsonian translocation carriers

Background

Preimplantation genetic diagnosis (PGD) is now widely used to select embryos free of chromosomal copy number variations (CNV) from chromosome balanced translocation carriers. However, it remains a difficulty to distinguish in embryos between balanced and structurally normal chromosomes efficiently.

Methods

For this purpose, genome wide preimplantation genetic haplotyping (PGH) analysis was utilized based on single nucleotide polymorphism (SNP) microarray. SNPs that are heterozygous in the carrier and, homozygous in the carrier’s partner and carrier’s family member are defined as informative SNPs. The haplotypes including the breakpoint regions, the whole chromosomes involved in the translocation and the corresponding homologous chromosomes are established with these informative SNPs in the couple, reference and embryos. In order to perform this analysis, a reference either a translocation carrier’s family member or one unbalanced embryo is required. The positions of translocation breakpoints are identified by molecular karyotypes of unbalanced embryos. The recombination of breakpoint regions in embryos could be identified.

Results

Eleven translocation families were enrolled. 68 blastocysts were analyzed, in which 42 were unbalanced or aneuploid and the other 26 were balanced or normal chromosomes. Thirteen embryos were transferred back to patients. Prenatal cytogenetic analysis of amniotic fluid cells was performed. The results predicted by PGH and karyotypes were totally consistent.

Conclusions

With the successful clinical application, we demonstrate that PGH was a simple, efficient, and popularized method to distinguish between balanced and structurally normal chromosome embryos.

     

Segregation of a complex rearrangement of chromosomes 6, 7, 8, and 12 through three generations

Summary In five healthy family members of three generations a reciprocal translocation, t(6;12)(q27;q21), combined with an inverted insertion inv ins (7;8)(p14;q22q13), has been demonstrated. Neither offspring with unbalanced karyotypes nor descendants with isolated translocations or insertions were observed. Five simultaneously occurring chromosomal breaks are considered to be the reason for the new rearrangement.     

Report of large kinship with familial translocation between chromosomes 21 and 22.

This paper reports a large kinship with a familial (21;22) translocation occurring in both the balanced and the unbalanced states. Recurrence risks for the (21;22) translocation in the unbalanced state are high (14%) for the offspring of female carriers as compared with those for the offspring of male carriers (4%), but the offspring of male carriers appear to have a much higher risk (50%) of being balanced carriers than those of female carriers (30%).     

A reciprocal translocation between autosomes 8 and 10 in a boar used for artificial insemination service and its effects on litter size.

The low number of piglets per litter was the reason why a Finnish Yorkshire breed boar used for artificial insemination (AI) was taken for cytogenetic study. The boar had a reciprocal translocation between autosomes 8 and 10, resulting in a reduction in its litter size of about 19%. In addition the litter sizes were counted from 16 female offspring of this 2n = 38,XY; rcp(8;10)(p1.1;q1.3) boar.     

Prenatal diagnosis and carrier detection of a cryptic translocation by using DNA markers from the short arm of chromosome 5.

DNA markers from the short arm of chromosome 5 were used to examine a large family in which a microscopically undetectable translocation was segregating. In addition to confirming that three retarded children were hemizygous for loci distal to 5p14, these analyses identified five individuals as being carriers of the balanced translocation. The use of molecular probes provided informed genetic counseling to the family for the first time. With the DNA markers from 5p, prenatal diagnosis was performed on two fetal chorionic villus samples, both of which were found to have unbalanced karyotypes. The identification of translocation carriers was complicated by recombination between the small translocated segment of 5p and the corresponding region on the normal homologue, which changed the haplotype of the translocated 5p segment.     

A new centric fusion translocation in cattle: rob (13;19)

A new Robertsonian translocation has been found in cattle. A bull from Marchigiana breed (central Italy) was found to be a heterozygous carrier of a centric fusion translocation involving cattle chromosomes 13 and 19 according to RBA-banding and cattle standard nomenclatures. CBC-banding revealed the dicentric nature of this new translocation, underlining the recent origin of this fusion. In fact, both the bull's parents and relatives had normal karyotypes. In vitro fertilization tests were also performed in the bull carrying the new translocation, in two bulls with normal karyotypes (control) and in four other bulls carrying four different translocations.