Cytogenetic survey in couples with recurrent fetal wastage

Summary Cytogenetic studies have been performed in 1068 couples with antecedent fetal wastage, i.e., at least two spontaneous first trimester abortions or one spontaneous first trimester abortion and one late fetal death, particularly with multiple congenital malformations.Three major types: 33 reciprocal translocations (3.09%), 20 Robertsonian translocations (1.87%) and six other chromosomal abnormalities (0.56%) were found, bringing the total number of chromosomal abnormalities to 59 (5.5%) in 1068 couples under investigation.In contrast to couples with reciprocal translocations, a high excess of female over male carriers was found in the group of Robertsonian translocations.In the evaluation of chromosomal polymorphisms, only variants with particularly large paracentromeric constitutive heterochromatin blocks were taken into account, and their low frequency in the present study is therefore not comparable with that in a general population.The impact of further extensive familial investigation on genetic counseling and the follow-up of prenatal diagnosis are discussed.     

Cytogenetic studies in 100 couples with recurrent spontaneous abortions.

The reported incidence of translocations in couples with recurrent spontaneous abortions ranges from 3% to 31% (average 9.3%). We report 100 couples in whom no reciprocal translocation carriers were ascertained.     

Structural chromosomal rearrangements in couples with repeated miscarriages. Experience in Louvain

In this paper we report our experience in the cytogenetic study of 1555 couples with recurrent first trimester fetal wastage. The frequency of chromosomal anomalies was found to be 6.36%, the majority of then (greater than 50%) being autosomal reciprocal translocations.     

The most frequent chromosomal abnormalities in karyotypes of patients with reproductive disorders

Cytogenetic and molecular cytogenetic characteristics have been studied in 210 couples with fertility problems. The patients’ karyotypes contained various chromosomal rearrangements in 46 cases (10.95%). The structural chromosomal rearrangements such as pericentric inversions, Robertsonian translocations, balanced reciprocal translocations, and marker chromosomes were more frequent than numerical chromosome aberrations (89.13 and 10.87% of cases, respectively). We have found 19 (4.52%) karyotypes with “hidden’ low mosaicism in X and Y chromosomes. We believe that the patients with chromosomal anomalies in the karyotype need differentiated treatment.     

Analysis of translocations observed in three different populations. I. Reciprocal translocations

A sample of 437 reciprocal translocations was classified into three groups according to their method of ascertainment (Group I = couples with repeated abortions; Group II = karyotypically unbalanced carriers; Group III = balanced translocation heterozygotes). Statistical analysis showed that the distributions of chromosome breaks observed in the three groups could not be accounted for by chromosome arm length alone. In couples with repeated abortions, an excess of breaks in 7p, 17p, and 22q was found, whereas in the balanced translocation heterozygotes an excess of breaks was found only in 11q. An excess of breaks was found in arms 9p, 14p, 18p, 18q, 21q, and 22q in karyotypically unbalanced probands. A significant decrease of breaks in the medial chromosome regions was accompanied by a concomitant increase in the terminal regions in all groups. The three groups demonstrated different distributions of chromosome arm involvement in the observed translocations. Balanced translocation heterozygotes had the highest frequency of large (greater than the length of 4p) translocated segments and an excess in the frequency of large-large translocations, whereas karyotypically unbalanced probands had the highest frequency of small (shorter than 21q) translocations and an excess in the frequency of small-small translocations. For each type of chromosomal imbalance observed, the balanced translocation heterozygotes demonstrated the greatest potential imbalance and the karyotypically unbalanced probands the least.     

Bilan des examens chromosomiques de 277 couples candidats à l’injection intracytoplasmique de spermatozoïde

In these study the frequency of congenital chromosomal aberrations was assessed in a sample of 277 couples included in a intracytoplasmic sperm injection (ICSI) program. A total of 7 aberrant karyotypes were diagnosed, corresponding to an abnormality rate of 1.3% per individual and 2.6% per couple. The following types of abnormalities were observed: reciprocal translocations (n=2), Robertsonian translocations (n=2), pericentral inversion (n=1), sex chromosomal mosaicism (n=1), marker chromosome (n=1). Surprisingly, 71% (5/7) of all abnormal karyotypes were contributed by the female partner of ICSI patients. These data confirm the higher incidence of chromosomal aberration in infertile couples compared with the baseline population risk. It also confirms that not only the male, but also the female should be routinely karyotyped prior to ICSI, and then receive appropriate genetic counselling.     

An excess of mental retardation and/or congenital malformations in carriers of reciprocal translocations. A difficult and delicate problem in genetic counseling

Excess of mental retardation and/or congenital malformations in reciprocal translocations in man. A difficult problem in genetic counselling: In this report the Leuven experience (1970-1984) on reciprocal translocations is summarized. A total number of 154 unrelated index-patients, carriers of different types of reciprocal translocations, and their families were investigated. The excess of MR/CM in de novo and familial balanced translocation carriers is illustrated and discussed.     

Excess of mental retardation and/or congenital malformation in reciprocal translocations in man

Summary In this report the Leuven experience (1970–1984) on reciprocal translocations is summarized. A total of 153 unrelated index patients, carriers of different types of reciprocal translocations, and their families were investigated. Familial reciprocal, apparently balanced translocations were found in 75 unrelated families bringing the total numbers of translocation carrier parents and their offspring to 132 and 445, respectively. In 61.5% of the patients the reciprocal translocation was detected after the birth of a malformed child with unbalanced karyotype or through investigation because of recurrent spontaneous abortions, stillbirths, or infertility. In 41 patients (28 familial and 13 de novo), however, the reciprocal balanced translocation was found to be associated with mental retardation and/or congenital malformations (MR/CM) which is significantly higher than expected. This excess of MR/CM in de novo and familial balanced translocation carriers is illustrated and discussed.     

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.     

Chromosomal distributions of breakpoints in cancer,infertility, and evolution

We extract 11 genome-wide sets of breakpoint positions from databases on reciprocal translocations, inversions and deletions in neoplasms, reciprocal translocations and inversions in families carrying rearrangements and the human-mouse comparative map, and for each set of positions construct breakpoint distributions for the 44 autosomal arms. We identify and interpret four main types of distribution: (i) a uniform distribution associated both with families carrying translocations or inversions, and with the comparative map, (ii) telomerically skewed distributions of translocations or inversions detected consequent to births with malformations, (iii) medially clustered distributions of translocation and deletion breakpoints in tumor karyotypes, and (iv) bimodal translocation breakpoint distributions for chromosome arms containing telomeric proto-oncogenes.     

Cytogenetic analysis in couples with recurrent miscarriages: a retrospective study from Punjab,north India

Human reproduction is considered as the most inefficient event as ～15–20% of human pregnancies end in miscarriage and in the product of miscarriages, chromosomal anomalies are a common occurrence. The aim of the present retrospective study was to assess the frequency of chromosomal aberrations in couples with recurrent miscarriages in the region of Punjab and to compare with worldwide frequencies. In this study, a total of 440 cases were referred between the period 1995–2015. After lymphocyte culturing, giemsa–trypsin banding was done for each case to assess the chromosomal anomalies. The frequency of chromosomal aberrations among couples was found to be 3.41% in our study. Among these aberrations, balanced reciprocal translocations formed the largest group with 60% anomalies. We would conclude that clinicians should understand the importance of chromosomal analysis in these couples and refer them for karyotyping after two miscarriages to rule out the possible genetic cause of recurrent miscarriages.     

A strategy for detecting chromosome-specific rearrangements in rye.

To obtain translocations involving specific chromosomes in rye, a line in which chromosome 1R has large C-bands on its two telomeres but which lacks C-bands (or has very small ones) on the telomeres of the remaining chromosomes was used. About 6% of the plants produced using pollen from irradiated (1.2 krad (1 rad = 10 mGy)) spikes of this line possessed structural changes involving the labeled chromosome. These aberrations included translocations, ring chromosomes, isochromosomes, and telocentrics. It is concluded (i) that all nonlabeled chromosomes have the same probability of participating in reciprocal translocations with the labeled chromosome, 1R, and (ii) that most induced reciprocal translocations involved exchanges of chromosome segments of approximately equal length. The use of lines having the appropriate combination of telomeric C-bands improves the efficiency of obtaining reciprocal translocations involving specific chromosomes that could be used in the construction of detailed physical maps.     

Value of silver staining technics for studying translocations involving acrocentric chromosomes

The silver-staining technique was used to study several cases of translocations involving acrocentric chromosomes: robertsonian translocations, balanced reciprocal translocations, non-reciprocal translocation. This technique provides very useful and reliable information about the presence, loss or translocation of active NORs in cases of acrocentric breaks.     

Reciprocal translocations in Saccharomyces cerevisiae formed by nonhomologous end joining

Reciprocal translocations are common in cancer cells, but their creation is poorly understood. We have developed an assay system in Saccharomyces cerevisiae to study reciprocal translocation formation in the absence of homology. We induce two specific double-strand breaks (DSBs) simultaneously on separate chromosomes with HO endonuclease and analyze the subsequent chromosomal rearrangements among surviving cells. Under these conditions, reciprocal translocations via nonhomologous end joining (NHEJ) occur at frequencies of approximately 2-7 x 10(-5)/cell exposed to the DSBs. Yku80p is a component of the cell's NHEJ machinery. In its absence, reciprocal translocations still occur, but the junctions are associated with deletions and extended overlapping sequences. After induction of a single DSB, translocations and inversions are recovered in wild-type and rad52 strains. In these rearrangements, a nonrandom assortment of sites have fused to the DSB, and their junctions show typical signs of NHEJ. The sites tend to be between open reading frames or within Ty1 LTRs. In some cases the translocation partner is formed by a break at a cryptic HO recognition site. Our results demonstrate that NHEJ-mediated reciprocal translocations can form in S. cerevisiae as a consequence of DSB repair.     

Most Uv-Induced Reciprocal Translocations in SORDARIA MACROSPORA Occur in or near Centromere Regions

In fungi, translocations can be identified and classified by the patterns of ascospore abortion in asci from crosses of rearrangement x normal sequence. Previous studies of UV-induced rearrangements in Sordaria macrospora revealed that a major class (called type III) appeared to be reciprocal translocations that were anomalous in producing an unexpected class of asci with four aborted ascospores in bbbbaaaa linear sequence (b = black; a = abortive). The present study shows that the anomalous type III rearrangements are, in fact, reciprocal translocations having both breakpoints within or adjacent to centromeres and that bbbbaaaa asci result from 3:1 disjunction from the translocation quadrivalent.-Electron microscopic observations of synaptonemal complexes enable centromeres to be visualized. Lengths of synaptonemal complexes lateral elements in translocation quadrivalents accurately reflect chromosome arm lengths, enabling breakpoints to be located reliably in centromere regions. All genetic data are consistent with the behavior expected of translocations with breakpoints at centromeres.-Two-thirds of the UV-induced reciprocal translocations are of this type. Certain centromere regions are involved preferentially. Among 73 type-III translocations, there were but 13 of the 21 possible chromosome combinations and 20 of the 42 possible combinations of chromosome arms.     

Mutagenic effect of different types of irradiation on the sex cells of male mice. IX. Duration of preservation of radiation-induced reciprocal translocations during the course of the reproductive period]

The rate of induction of reciprocal translocations by gamma-irradiation of mouse spermatogonia was studied by cytological examination of descendent spermatocytes. The CBA mice were given a total single acute dose of 300 r or 3 times per 300 r with 7 and 28 days intervals. The irradiated mice were killed within 3,7 and 12 month after the irradiation. The frequency of translocations in 3 and 7 month after the treatment was the same. A 25% decrease in the yield of reciprocal translocations was observed in 12 months after the irradiation. It suggests that the genetic risk from ionizing radiation remains high a year after the irradiation.     

Possible excess of mental handicap and congenital malformations in autosomal reciprocal translocations.

The most pertinent data of the 32 cases of reciprocal autosomal translocations detected in the laboratory since the initiation of the banding-techniques are summarized. One third of these balanced translocations were detected in patients presenting with mental handicap and/or malformative symptoms.     

Reciprocal translocations in mice found in the vicinity of the Chernobyl nuclear power station

A study was made of the incidence of genetic damage to germ cells of male mice taken from or exposed within the thirty-kilometer zone of Chernobyl, the contaminated no-man's-land around the reactor that failed. At all contamination levels mouse spermatocytes exhibited reciprocal translocations, a relatively low frequency of which increased with increasing dose rate. Heterozygotes, with respect to reciprocal translocations (5%), were found among males exposed to enhanced radiation background as early embryos.     

Meiotic association between the XY chromosomes and the autosomal quadrivalent of a reciprocal translocation in two infertile men, 46,XY,t(19;22) and 46,XY,t(17;21)

An electron microscopy study of synaptonemal complexes in two men carrying reciprocal translocations, a t(19;22) and a t(17;21), is reported. It is shown that a delay in synapsis affects the segments corresponding to the short arms of the acrocentrics involved in the formation of quadrivalents. This appears to provoke an interaction with the sex bivalent which could lead to a failure of spermatogenesis. A study of the literature comparing reciprocal translocations that do and do not involve acrocentrics in sterile and fertile men shows the existence of a significant association between the presence of an acrocentric in the rearrangement and sterility. These results on reciprocal translocations involving at least one acrocentric chromosome correspond to those obtained in cases of Robertsonian translocations.     

Non random position of metaphasic chromosomes: A study of radiation induced and constitutional chromosome rearrangements

Summary The rearranged chromosomes derived from reciprocal translocations or dicentric-acentric formations, observed 48 h after their induction by irradiation at Go phase, have a clear tendency to be closer together than their normal homologues. This tendency disappears in longer cultures, and does not exist when many different constitutional reciprocal translocations are considered together. It indicates that the chromosomes having exchanged segments remain adjacent at the following metaphase, and thus, that metaphase plates reflect, at least partially, the interphase arrangement of chromosomes.