Meiotic segregation of human sperm chromosomes in translocation heterozygotes: report of a t(9;10)(q34;q11) and a review of the literature

Meiotic segregation products were studied in sperm from a man who was heterozygous for a reciprocal translocation, t(9;10)(q34;q11). A total of 171 sperm chromosome complements were studied by in vitro fertilization of hamster eggs. All possible 2:2 and 3:1 meiotic segregations were observed with the following frequencies: alternate, 41%; adjacent-1, 48%; adjacent-2, 5%; 3:1, 6%. Within alternate segregations, the number of normal sperm (35) was not significantly different from the number of sperm carrying a balanced form of the translocation (33), as expected. The proportion of sperm with an unbalanced form of the translocation was 60%. There was no evidence for an interchromosomal effect, since the frequencies of numerical (8%) and structural (15%) chromosomal abnormalities (both unrelated to the translocation) were within the normal range of control donors. The literature on a total of 10 translocation heterozygotes studied by sperm chromosome analysis was reviewed.     

Partial trisomy 17q and monosomy 9p due to a familial translocation.

Described is an infant with partial trisomy 17q and monosomy 9p [46,XX,-9,+der(9)t(9;17)(p21;q23)] due to adjacent-1 segregation of a maternal balanced reciprocal translocation. Characteristic clinical features of both partial 17q trisomy and monosomy 9p are present, but the former syndrome is less recognisable in this infant than in previously reported cases due to the concomitant 9p monosomy.     

Familial Down syndrome due to t(10;21) translocation: evidence that the Down phenotype is related to trisomy of a specific segment of chromosome 21.

This report deals with a reciprocal t(10;21) translocation which is observed in three generations of a family. Included are examples of the balanced translocation, adjacent-2 segregation producing three patients with trisomy of the distal long arm of chromosome 21 and the Down syndrome, and 3-1 disjunction producing trisomy of the proximal segment of chromosome 21 in a mildly mentally retarded boy without phenotypic features of the Down syndrome. These data provide evidence that the Down phenotype is attributable to trisomy of the distal long arm of chromosome 21.     

Meiotic chromosome segregation in human t(11;22)(q23;q11) carriers: a theoretical consideration

The t(11;22)(q23;q11) translocation is the most frequently encountered familial reciprocal translocation in humans. In the majority of reported cases ascertainment has been through the birth of a child with the chromosomal constitution 47,XX,+der(22) or 47,XY,+der(22), i.e., tertiary trisomy. Previous segregation analysis of familial cases showed a number of interesting features. Thus, euploid unbalanced genotypes resulting from adjacent segregation are absent in the progeny, and only tertiary trisomic offspring are recovered. To explain this unusual progeny output we present here a model for the meiotic behavior of this translocation in the carriers based on an analysis of cytogenetic data of progeny of carriers. This model predicts the formation of a chain trivalent with chromosome order 11-der(11)-22 during prophase I and its predominant alternate orientation at metaphase I.     

A family with segregation of an unbalanced translocation (7;13) (q36;q32) in three patients with severe mental retardation, microcephaly and dysmorphic features, detected by subtelomere FISH: genetic counselling and prenatal diagnosis

We report a Sardinian family in which three members showed a mental-retardation-microcephaly-multiple malformations syndrome resulting from an unbalanced translocation (7;13)(q36;q32) which led to subtelomeric trisomy 7q36qter and partial monosomy 13q32qter. The unbalanced translocation was transmitted by alternate segregation from a female and a male carriers of the balanced translocation. The three patients had severe mental retardation, microcephaly and multiple minor facial and fingers anomalies. Neuroimages showed brain atrophy, associated in two patients with partial agenesis of the corpus callosum. FISH with chromosome 13 and 7 specific painting probes and subtelomere specific probes was instrumental for defining and characterizing the chromosomal translocation. Extensive genetic counseling and prenatal diagnosis has been offered to all the members of the family.     

Meiotic segregation, recombination, and gamete aneuploidy assessed in a t(1;10)(p22.1;q22.3) reciprocal translocation carrier by three- and four-probe multicolor FISH in sperm.

Meiotic segregation, recombination, and aneuploidy was assessed for sperm from a t(1;10)(p22.1;q22.3) reciprocal translocation carrier, by use of two multicolor FISH methods. The first method utilized three DNA probes (a telomeric and a centromeric probe on chromosome 1 plus a centromeric probe on chromosome 10) to analyze segregation patterns, in sperm, of the chromosomes involved in the translocation. The aggregate frequency of sperm products from alternate and adjacent I segregation was 90.5%, and the total frequency of normal and chromosomally balanced sperm was 48.1%. The frequencies of sperm products from adjacent II segregation and from 3:1 segregation were 4.9% and 3.9%, respectively. Reciprocal sperm products from adjacent I segregation deviated significantly from the expected 1:1 ratio (P < .0001). Our assay allowed us to evaluate recombination events in the interstitial segments at adjacent II segregation. The frequencies of sperm products resulting from interstitial recombination in chromosome 10 were significantly higher than those resulting from interstitial recombination in chromosome 1 (P < .006). No evidence of an interchromosomal effect on aneuploidy was found by use of a second FISH method that simultaneously utilized four chromosome-specific DNA probes to quantify the frequencies of aneuploid sperm for chromosomes X, Y, 18, and 21. However, a significant higher frequency of diploid sperm was detected in the translocation carrier than was detected in chromosomally normal and healthy controls. This study illustrates the advantages of multicolor FISH for assessment of the reproductive risk associated with translocation carriers and for investigation of the mechanisms of meiotic segregation of chromosomes.     

Fertility of male and female mice heterozygous for the reciprocal translocation T(7;17)3BKM.

The present paper describes the fertility of male and female mice heterozygous for the reciprocal translocation T(7;17)3BKM. This translocation was induced by gamma rays in the spermatozoa of an irradiated parent. It is characterized by "asymmetrical" localization of the breakpoints, distally in Chromosome 7 (7F5) and proximally in Chromosome 17 (17B1). The data presented here relate only those matings in which, for both partners, heterozygosity or normality could be confirmed cytogenetically. The results indicate that both male and female translocation heterozygotes are fertile, their mean litter size being reduced to about 50% of that of normal littermates. This leads to the conclusion that the multivalents mainly undergo either alternate or adjacent-1 2:2 segregation. No viable tertiary trisomics were observed among the progeny of the translocation carriers. Analysis of the frequency of the different types of multivalents in diakinesis-metaphase I spermatocytes showed a significant predominance of chain-type figures (CIV and CIII+I), with chains of four elements (CIV) being more frequent than other configurations. This demonstrates that the small marker chromosome remains attached by one of its segments to the tetravalent.     

Chromosome segregation in mice heterozygous for Robertsonian translocations. II. Changes in the structure of homologs as a cause of abnormal disjunction in females

It was demonstrated that mutations T, Fu, Ki, t6 of chromosome 17 cause preferential transmission of the acrocentric homologues to the progeny from female Rb heterozygotes. The results indicate that the effects of these mutations on segregation are restricted to the Robertsonian translocations involving chromosome 17. Substitution of the parts of chromosome 17 distal or proximal to the T-locus did not alter the effect, of this chromosome on the transmission rate of the homologue. The transmissions effects of these mutations, whether cis or trans with Rb, were the same. It was observed that mothers Rb7/T43H transmitted the chromosome with the reciprocal translocation T43H to 70.9% of their progeny. Data were obtained supporting the idea that structural changes of the chromosomes caused by mutations affect segregation of the homologues in Rb heterozygous females. The possible mechanism of this influence is discussed.     

Sperm chromosome analysis of two men heterozygous for reciprocal translocations: t(1;9)(q22;q31) and t(16;19)(q11.1;q13.3).

Sperm chromosome complements were analysed in two men who were heterozygous carriers of reciprocal translocations. A total of 363 sperm were karyotyped after in vitro penetration of hamster oocytes, including 180 sperm from a male with a t(1;9)(q22;q31) and 183 from a male with a t(16;19)(q11.1;q13.3). All possible 2:2 and 3:1 meiotic segregations were observed for both translocations. The frequencies of alternate, adjacent 1, adjacent 2, and 3:1 segregations were 46%, 38%, 13%, and 4% for the t(1;9) and 40%, 28%, 31%, and 1% for the t(16;19), respectively. Within the alternate segregation group, the number of normal sperm was not significantly different from the number of sperm carrying a balanced form of the translocation for either of the translocations, as expected. There was no evidence for an interchromosomal effect of either translocation, since the frequencies of numerical abnormalities unrelated to the translocation were within the normal range observed in sperm from control donors. The percentage of sperm with an unbalanced form of the translocation was 54% for the t(1;9) and 61% for the t(16;19).     

Role of heterochromatin during preferential 9q;22q translocation in chronic myelogenous leukemia

The secondary constriction region (h) of human chromosome 9 was evaluated in 55 chronic myelogenous leukemia (CML) patients with respect to its size and position. Each case was examined by C-banding and distamycin A-4,6-diamidino-2-phenylindole techniques for the expression of the h regions. When one h region of chromosome 9 was larger, it was more frequently involved in the reciprocal translocation with chromosome 22. In addition, there was a higher incidence of pericentric inversions in the h regions in the translocated chromosome 9 when compared with normal homologues. The role of the constitutive heterochromatin of chromosome 9 as a possible influencing factor during 9q;22q translocation in CML is suggested.     

Chromosome segregation into the spermatozoa of two men heterozygous for different reciprocal translocations

Sperm chromosomes from two human males, each heterozygous for a different reciprocal translocation, were examined. Chromosomally normal sperm were found in equal numbers to those carrying the translocation in the balanced form, in both males. Alternate segregation was more common than adjacent segregation in both translocations. Male W. G. had a greater proportion of sperm containing chromosome abnormalities unrelated to the translocation than did J.S., the second made studied. J.S. however, had a greater frequency of chromosomally unbalanced sperm. The great majority of unbalanced sperm in both males was due to adjacent I segregation.     

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.     

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.     

Human X-autosome translocations: differential inactivation of the X chromosome in a kindred with an X-9 translocation.

A kindred with an X-autosome translocation and differential inactivation of the X chromosome is described. The phenotypically normal mother has a reciprocal translocation [46,X,rcp(X;9) (q11;q32)] while the daughter's karyotype is unbalanced [46,X,--X,+der(9),rcp(X;9) (q11;q32)mat], indicating adjacent-two type of segregation in the mother. In the mother's cells the normal X is late replicating, while in the daughter's cells almost the entire der(9) is late replicating, indicating the presence of autosomal inactivation. The daughter's abnormal phenotype can be explained by her sex chromosomal complement and the absence of effective trisomy 9. At this stage there is no simple explanation to account for all types of inactivation patterns encountered in the 14 balanced and 15 unbalanced cases of X-autosome translocations reported to date. Selection of X inactivation is not an inherent characteristic of the X chromosome per se, and it is not dependent on the direction of chromosomal exchange, as was suggested previously. Correlation of the phenotypic and cytogenetic features of these patients suggests a pattern of X and autosomal inactivation consistent with the least amount of genotypic and phenotypic imbalance in most cases. The data are most consistent with random X inactivation followed by selection of the most viable cell line.     

Analysis of meiotic segregation in a man heterozygous for a 13;15 Robertsonian translocation and a review of the literature

Summary Meiotic segregation was studied in a male heterozygous for a 13;15 Robertsonian translocation using in vitro sperm penetration of hamster eggs. Sixty-seven sperm chromosome complements were obtained and R-banded. Alternate segregation produced equal numbers of normal (31) and balanced (29) gametes, as was theoretically expected. Incidence of unbalanced complements was 10.4%, and the frequency of abnormalities unrelated to the translocation was 7.4%. This study confirms the predominance of alternate meiotic segregation in Robertsonian translocation carriers. Four sperm studies of Robertsonian translocation have been previously reported. A review of the combined results points out the low incidence of imbalance in the sperm of Robertsonian translocation carrier and the lack of evidence for an interchromosomal effect.     

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.     

Physical distribution of translocation breakpoints in homoeologous recombinants induced by the absence of the Ph1 gene in wheat and triticale

The physical distribution of translocation breakpoints was analyzed in homoeologous recombinants involving chromosomes 1A, 1B, 1D of wheat and 1R of rye, and the long arms of chromosome 7S of Aegilops speltoides and 7A of wheat. Recombination between homoeologues was induced by removal of the Ph1 gene. In all instances, translocation breakpoints were concentrated in the distal ends of the chromosome arms and were absent in the proximal halves of the arms. The relationship between the relative distance from the centromere and the relative homoeologous recombination frequency was best explained by the function f(x)=0.0091e^0.0592x. The pattern of recombination in homoeologous chromosomes was essentially the same as in homologues except that there were practically no double exchanges. Among 313 recombinant chromosomes, only one resulted from a double crossing-over. The distribution of translocation breakpoints in translocated arms indicated that positive chiasma interference operated in homoeologous recombination. This implies that the reduction of the length of alien chromosome segments present in translocations with wheat chromosomes may be more difficult than the production of the original recombinants.     

Homologous recombination and transposition generate chromosome I neopolymorphism during meiosis in Saccharomyces cerevisiae

We have studied the meiotic segregation of a chromosome length polymorphism (CLP) in the yeast Saccharomyces cerevisiae. The neopolymorphism frequently observed within the smallest chromosomes (I, VI, III and IX) is not completely understood. We focused on the analysis of the structure of chromosome I in 88 segregants from a cross between YNN295 and FL100trp. Strain FL100trp is known to carry a reciprocal translocation between the left arm of chromosome III and the right arm of chromosome I. PCR and Southern hybridization analyses were performed and a method for the rapid detection of chromosome I rearrangements was developed. Seven chromosome I types were identified among the 88 segregants. We detected 22 recombination events between homologous chromosomes I and seven ectopic recombination events between FL100trp chromosome III and YNN295 chromosome I. These recombination events occurred in 20 of the 22 tetrads studied (91%). Nine tetrads (41%) showed two recombination events. This showed that homologous recombination involving polymorphic homologues or heterologous chromosomes is the main source of neopolymorphism. Only one of the seven chromosome I variants resulted from a transposition event rather than a recombination event. We demonstrated that a Ty1 element had transposed within the translocated region of chromosome I, generating mutations in the 3′ LTR, at the border between U5 and PBS. Received: 7 May 1999 / Accepted: 14 February 2000     

9;21相互易位携带者生育多例9p部分三体患者细胞遗传学分析

在河南南阳收集到一个家系4代23人, 其中6人患先天性智力障碍, 具有轻度的面部和小母指畸形等特点, 先证者伴随有癫痫的发生。采用常规的外周血培养染色体G带分析, 发现先证者的核型为：46, XY, der(21) t(9; 21) (9p22.2; 21q22.3)pat, 是部分9p三体。对该家系其他成员的染色体进行分析, 发现所有患者均为部分9p三体, 异常染色体均来自9号与21号染色体平衡易位携带者染色体相互易位的异常分离, 因此这是一个部分9p三体综合征家系。而重复区段发生在9号染色体短臂远端一半区域(9pter→9p21)内, 该区是关键区, 导致智力障碍和面容轻微畸形。