Tertiary Trisomics Research Articles

Two Novel Cases of Autosomal Translocations in the Horse: Warmblood Family Segregating t(4;30) and a Cloned Arabian with a de novo t(12;25)

We report 2 novel autosomal translocations in the horse. In Case 1, a breeding stallion with a balanced t(4p;30) had produced normal foals and those with congenital abnormalities. Of his 9 phenotypically normal offspring, 4 had normal karyotypes, 4 had balanced t(4p;30), and 1 carried an unbalanced translocation with tertiary trisomy of 4p. We argue that unbalanced forms of t(4p;30) are more tolerated and result in viable congenital abnormalities, without causing embryonic death like all other known equine autosomal translocations. In Case 2, two stallions produced by somatic cell nuclear transfer from the same donor were karyotyped because of fertility issues. A balanced translocation t(12q;25) was found in one, but not in the other clone. The findings underscore the importance of routine cytogenetic screening of breeding animals and animals produced by assisted reproductive technologies. These cases will contribute to molecular studies of translocation breakpoints and their genetic consequences in the horse.

Tertiary trisomics in 2n = 12 Coix taxon

Tertiary trisomics have been isolated from the domesticated outcrossed population of a comparatively new taxon of Coix with 2n = 12 chromosome number and also from the selfed progenies of the chromosomal variants ranging from 2n=11 to 2n=13. Cytological analysis of these trisomics indicated that different chromosomal associations forming a trivalent, pentavalent and univalent were frequent at diakinesis. Disomics (2n = 12) and their monosomics (2n-1; 2n = 11) showing interchanged quadrivalents at diakinesis were observed to be the main sources of these tertiary trisomics.

Transcriptional consequence and impaired gametogenesis with high-grade aneuploidy in Arabidopsis thaliana.

Aneuploidy features a numerical chromosome variant that the number of chromosomes in the nucleus of a cell is not an exact multiple of the haploid number, which may have an impact on morphology and gene expression. Here we report a tertiary trisomy uncovered by characterizing a T-DNA insertion mutant (aur2-1/+) in the Arabidopsis (Arabidopsis thaliana) AURORA2 locus. Whole-genome analysis with DNA tiling arrays revealed a chromosomal translocation linked to the aur2-1 allele, which collectively accounted for a tertiary trisomy 2. Morphologic, cytogenetic and genetic analyses of aur2-1 progeny showed impaired male and female gametogenesis to various degrees and a tight association of the aur2-1 allele with the tertiary trisomy that was preferentially inherited. Transcriptome analysis showed overlapping and distinct gene expression profiles between primary and tertiary trisomy 2 plants, particularly genes involved in response to stress and various types of external and internal stimuli. Additionally, transcriptome and gene ontology analyses revealed an overrepresentation of nuclear-encoded organelle-related genes functionally involved in plastids, mitochondria and peroxisomes that were differentially expressed in at least three if not all Arabidopsis trisomics. These observations support a previous hypothesis that aneuploid cells have higher energy requirement to overcome the detrimental effects of an unbalanced genome. Moreover, our findings extend the knowledge of the complex nature of the T-DNA insertion event influencing plant genomic integrity by creating high-grade trisomy. Finally, gene expression profiling results provide useful information for future research to compare primary and tertiary trisomics for the effects of aneuploidy on plant cell physiology.

Partial trisomy 1q41‐qter and partial trisomy 9pter‐9q21.32 in a newborn infant: An array CGH analysis and review

We report on a girl who presented with distinctive abducted hip and hyperextended knee. Cytogenetic analysis detected an extra derivative chromosome resulting from a balanced translocation in the mother and 3:1 segregation. Using array comparative genomic hybridization (CGH) in combination with conventional high resolution GTG banding, we designate the karyotype as 47, XX, +der(9)t(1;9)(q41;q21.32)mat, indicating tertiary trisomy of chromosome segments 1q41-qter and 9pter-9q21.32. A review and genotype-phenotype correlation suggested that the patient represented most of the manifestations of duplication of chromosome arms 1q and 9p. To our knowledge, a similar case has so far not been reported.

Preimplantation genetic diagnosis for X;autosome translocations: lessons from a case of misdiagnosis

Preimplantation genetic diagnosis (PGD) is offered to couples carrying a reciprocal translocation in an attempt to increase their chance of phenotypically normal offspring. For the selection of embryos that are balanced for the translocation chromosomes, it is critical to use a combination of DNA probes that can take account of all the segregation patterns of the particular translocation. The frequency of the different segregation types differs depending on the chromosomes involved, the location of the breakpoints and the number of chiasmata and the sex of the carrier. We report on a case of misdiagnosis after PGD-fluorescence in situ hybridization in a female translocation 46,X,t(X;5)(q13;p14) carrier. Transfer of two embryos diagnosed as balanced for the translocation chromosomes resulted in a singleton pregnancy that miscarried at 8 weeks' gestational age. The unbalanced karyotype of the fetus was consistent with 3:1 segregation resulting in tertiary trisomy for the derivative chromosome 5: 47,XX,+der(5)t(X;5)(q13;p14)mat. Based on additional molecular cytogenetic studies of fetal tissue and the initially investigated blastomeres, we concluded that the misdiagnosis was most probably due to a technical error, i.e. a partial hybridization failure or co-localization of the Xq/Yq subtelomere probe signals. No evidence for a normal cell line (mosaicism) was found in the fetus, which could have explained the discrepancy. This case demonstrates the importance of using two diagnostic probes or testing 2 cells to detect translocation products with potentially viable imbalance. X;autosome translocations are a special case due to the added complication of X chromosome inactivation and particular caution is advised when designing a PGD strategy. not applicable.

A prenatal tertiary trisomy resulting from balanced maternal 8; 9 translocation

An additional derivative chromosome 8 was found in the cytogenetic analyses of the chorionic villus biopsy specimen of a balanced reciprocal translocation carrier mother. This was a 3:1 segregation of the unbalanced product of the balanced maternal 8:9 translocation. The chromosomes of the carrier of the balanced reciprocal translocation pair with their matching homologous segments at meiosis I, a quadrivalent figure is formed and chromosomes segregate from this configuration. Increased nuchal tranaslucency was also determined on fetal sonography at the 13(rd) week of gestation. The final karyotype was 47,X Y,+der(8)t(8;9)(q11.2;p22) mat, and the parents were informed about this tertiary trisomy. After genetic counseling, the parents decided to terminate the pregnancy. The presented case is a reminder of the probability of the unbalanced products of the 3:1 segregation, rather than the common 2:2 segregation.

Unbalanced reciprocal translocations at amniocentesis

Objective To present perinatal findings, modes of ascertainments, and modes of segregation in unbalanced reciprocal translocations detected at amniocentesis. Materials and Methods Between January 1987 and July 2010, 40 cases with unbalanced reciprocal translocations were diagnosed by amniocentesis at Mackay Memorial Hospital, Taipei, Taiwan. The 40 cases originated from 29 families; 21 families with one case, 7 families with two cases, and 1 family with five cases. Results Of 40 cases, 33 (82.5%) presented fetal ultrasound abnormalities and 7 (17.5%) presented no ultrasound abnormalities. Of 40 cases, 36 (90%) had a segregation mode of adjacent-1 2:2 segregation, 3 (7.5%) had a segregation mode of 3:1 segregation with tertiary trisomy, and 1 (2.5%) had a segregation mode of 3:1 segregation with tertiary monosomy. Of 29 families, 7 (24.1%) had de novo translocations and 22 (75.9%) had inherited translocations. In seven de novo cases, the main modes of ascertainments included abnormal ultrasound findings ( n = 5) and advanced maternal age ( n = 2). In 22 inherited families, the main modes of first ascertainment included abnormal ultrasound findings ( n = 8), a previous aneuploid child ( n = 8), advanced maternal age ( n = 4), parental carrier status ( n = 1), and abnormal maternal serum screening results ( n = 1). Among 22 inherited families, 9 (40.9%) had a known parental carrier status, but 13 (59.1%) were unaware of parental carrier status at amniocentesis. Conclusion Unbalanced reciprocal translocations detected at amniocentesis are frequently associated with abnormal ultrasound findings. Prenatal diagnosis of an unbalanced translocation may incidentally detect a balanced translocation in the family. Prenatal diagnosis of fetal structural abnormalities should alert structural chromosome rearrangements and prompt cytogenetic analysis of the fetus and parents if necessary.

Recent progress on genetic analysis of novel mutants and aneuploid research in grass pea (Lathyrus sativus L.)

A good number of diploid genetic mutants, RILs and different cytogenetic stocks including a complete set of primary trisomics and tetrasomics, some tertiary trisomics, double trisomics and 10 reciprocal translocation lines were developed and being characterized in induced mutant population of seven different grass pea (Lathyrus sativus L.) varieties. Genetic basis of mutants has been investigated in intercrossed population and using trisomics some of them were localized on chromosome. Utilization of these novel genetic and cytogenetic stocks in improvement of grass pea with high yield and low seed neurotoxin, ODAP potential has been reviewed in this communication. Key words: Grass pea (Lathyrus sativus L.), recombinant inbred lines (RILs), ODAP.

Maize tertiary trisomic stocks derived from B-A translocations.

Reciprocal translocations between supernumerary B chromosomes and the basic complement of A chromosomes in maize have resulted in a powerful set of tools to manipulate the dosage of chromosomal segments. From 15 B-A reciprocal translocation stocks that have the B-A chromosome genetically marked we have developed tertiary trisomic stocks. Tertiary trisomics are 2n + 1 aneuploids where the extra chromosome is a translocation element, in this case a B-A chromosome. Whereas B-A translocations produce aneuploidy in the sperm, the tertiary trisomic plant efficiently transmits hyperploid gametes maternally. Because the B-A tertiary trisomic stocks and the B-A translocation stocks from which they were derived are introgressed into the W22 inbred line, the effects of maternally and paternally transmitted trisomic B-A chromosomes can be compared. Data are presented on both the male and female transmission rates of the B-A chromosomes in the tertiary trisomic stocks.

Gonadal development and birth weight in X*X and X*Y females of the wood lemming, Myopus schisticolor

A quantitative histological analysis of ovaries from 8- to 10-day-old wood lemmings revealed significant differences between females with X*Y and X*X sex chromosome constitutions. The ovarian volume of X*Y females was on average 57% of X*X, and the number of oocytes was less than half in X*Y compared to X*X. However, the frequency of growing oocytes in relation to the total number was 6.5% for X*Y compared to 3.0% for X*X. Oogenesis in X*Y wood lemmings resembles in many respects that of mice heterozygous for certain translocations and with tertiary trisomy (Ts31H), and those with X0 monosomy. The fertility in X*Y wood lemmings is not reduced. On the contrary, X*Y females have a higher reproductive fitness than X*X and XX. This is discussed in relation to the present findings. The body weight at birth was 8% higher in X*Y than in X*X.

Genetic Diversity among Plantagos XXXI. A Tertiary Trisomic of Plantago ovata. Nature, Behaviour and Origin.

A plant was isolated from the progeny of a cross between a translocation heterozygote mother and disomic pollen donor which carried an additional chromosome (2x+ 1) in all cells of the root tip and sporogenous tissue. The chromosome was unlike any in the standard chromosome complement. The nature and synaptic behaviour of this chromosome suggest that the aneuploid is a tertiary trisomic. The posible mode of origin of the extra chromosome and the aneuploid plant have been discussed.

Cytogenetical gene mapping by reciprocal translocation and tertiary trisomic analyses in rice (Oryza sativa L.).

The orientation of RFLP linkage map and the assignment of RFLP markers to the restricted chromosomal segment were determined on seven pachytene chromosomes (1, 3, 4, 5, 8, 9 and 12) of rice. A total of 24 interchange breakpoints were detected by pachytene analysis of reciprocal translocation (RT) heterozygotes derived from crosses between 12 RT lines and normal diploid varieties. Further, 19 strains of japonica-indica hybrid tertiary trisomics were developed and provided for RFLP gene dosage analysis, resulting in locating 32 breakpoints of the extra tertiary chromosomes within genetic linkage segments defined by RFLP markers. From these results, the orientation of RFLP linkage groups on pachytene chromosomes and the assignment of 113 RFLP markers and four cloned rice genes to chromosome arms were conducted, together with the delimitation of centromeres on 6 RFLP linkage groups (1, 3, 4, 8, 9 and 12). Meanwhile, 15 groups of RFLP markers were incorporated with the restricted segments of pachytene chromosome. Compared with RFLP map, the physical distance of a part of the long arm of chromosome 1 was 5.4 to 8.8 cM/μm at the pachytene stage.

Cytological identification of some trisomics of Russian wildrye (Psathyrostachys juncea)

Russian wildrye, Psathyrostachys juncea (Fisch.) Nevski (2n = 2x = 14; NsNs), is an important forage grass and a potential source of germplasm for cereal crop improvement. Because of genetic heterogeneity as a result of its self-incompatibility, it is difficult to identify trisomics of this diploid species based on morphological characters alone. Putative trisomies (2n = 2x + 1 = 15), derived from open pollination of a triploid plant by pollen grains of diploid plants, were characterized by Giemsa C-banding. Based on both karyotypic criteria and C-banding patterns, four of the seven possible primary trisomics, a double-deletion trisomic, and two tertiary trisomics were identified.

Aneuploid and other cytological tester sets in rye

Cytological tester sets include series of aneuploids (nullisomics, monosomics, trisomics of different types, tetrasomics), series of rearranged chromosomes (translocations, inversions, duplications, deficiencies) and series of chromosomes recognizable by specific microscopically visible markers (C- or other banding, molecular markers). In rye, only a few (mainly tertiary and telocentric) monosomics and no viable nullisomics have been found. Several sets of primary trisomics and some telocentric sets, usually not fully complete, have been developed, but few are still available for gene localization. A few tertiary trisomics have been derived from translocation heterozygotes. Extensively used are different sets of additions of rye chromosomes to wheat. A relatively widely distributed set of marked chromosomes is the Wageningen translocation tester set, complemented with translocations from different other institutions. A disadvantage of rye translocations is insufficient heterozygote semisterility. Series of otherwise rearranged chromosomes have not been reported. Sets of lines with chromosomes conspicuously differing from the standard C-banding pattern have been obtained. Molecular markers are available for most rye chromosome, but lack of heterozygosity, necessary for classification after in situ hybridization is a restriction for use as cytological testers. In the cases of most translocations, C-banding and in situ molecular markers, each separate plant in a segregating population must be screened cytologically, whereas with aneuploid markers or with translocations having sufficient heterozygote semisterility, analyzing segregations is sufficient.

Spontaneous structural rearrangements in Solanum phureja Juz. et Buk. 2. Meiotic behaviour and identification of interchange chromosomes using primary trisomics

Meiosis was studied in two diploid (2n = 2x = 24) siblings of Solanum phureja Juz. et Buk. and in 11 disomic and 2 trisomic descendants. The diploid siblings carry the same heterozygous interchange and either one or two inversions. The frequency of quadrivalents at diakinesis/metaphase I in these clones was 0.56 and 0.62 per pollen mother cell. In two plants from the first inbred generation (I1) this frequency was about the same but in some other I1 plants and a full sib the frequency was substantially lower, varying from 0.00 to 0.16. Most quadrivalents, 78-83%, were rings. A variety of quadrivalent configurations at diakinesis and metaphase I was observed, giving rise to balanced and unbalanced gametes. The absence of ring quadrivalents in trisomic descendants of one of the siblings implied that tertiary trisomics or primaries being homozygous for the interchange were present in the I1 generation. Regular chromosome distribution (12-12) at anaphase I occurred in 46.5 and 73.2% of the pollen mother cells studied in the two original clones. Irregularities, such as 11-13 distribution, lagging chromosomes, and a bridge and fragment, were detected on average in 2.7, 3.3, and 32.5%, respectively, of the anaphase I cells analysed. In hybrids from crosses between 6 primary trisomics as females with the interchange heterozygote, the involvement in the interchange of chromosomes 3 and 12 was clearly demonstrated.

Cytogenetic analysis of malformed mouse fetuses derived from balanced translocation heterozygotes

Reciprocal translocations are readily induced by various physical and chemical mutagens in certain germ-cell stages. Carriers of balanced reciprocal translocations generally exhibit no abnormal phenotypes, except for occasional male sterility, but about half (on average) of their progeny carry grossly unbalanced chromosome complements and die prenatally, so that the carriers are said to be 'semisterile'. Since death of such progeny generally occurs in very early embryonic stages, it would be of minor importance in an analogous human situation. Several types of unbalanced segregants, however, survive to late gestational or even to postnatal stages and are often malformed. Recently, it was determined in this laboratory that over one half of the male carriers of methylene-bisacrylamide-induced translocations, sired litters that had late-dying and/or malformed fetuses (Rutledge et al., 1990). Five high-anomaly translocation stocks derived from that study and four derived from studies with other mutagens were analyzed cytogenetically to determine (1) the chromosomes and breakpoints involved, (2) the nature of chromosome imbalance in malformed fetuses, and (3) the types of meiotic segregation that produce late-surviving unbalanced segregants. Cytogenetic analysis of the 9 translocation stocks revealed 18 breakpoints located in 12 chromosomes. Each translocation had at least one breakpoint located near the centromere or the telomere. All translocations produced abnormal fetuses that were partially monosomic for a very short terminal chromosome segment, and partially trisomic for a segment that can be of various lengths, 2-10 times as long as the monosomic segment. In 6 stocks, these abnormal fetuses arose by adjacent-1 or alternate segregation; in the other three they arose by adjacent-2 segregation. In addition, tertiary trisomy by 3-1 missegregation was also observed in two of the stocks.

Production of Tertiary Trisomics in Rice(Oryza sativa L.).

Production of Tertiary Trisomics in Rice(Oryza sativa L.).

Duplication/deficiency mapping of situs inversus viscerum ( iv), a gene that determines left-right asymmetry in the mouse

A recessive mutation in the mouse, situs inversus viscerum (iv), results in randomization of organ position along the left-right body axis: approximately 50% of the progeny of homozygous matings exhibit situs solitus and 50% exhibit situs inversus. Recent studies have established genetic linkage between iv and the immunoglobulin heavy chain gene complex (Igh-C), located on distal mouse chromosome 12. In the present study, we have refined the genetic map location of iv relative to the breakpoint of a reciprocal translocation, T(5;12)31H, involving the telomeric region of chromosome 12 distal to Igh-C and the proximal region of chromosome 5. The translocation results in a large 12(5) derivative chromosome and a small 5(12) derivative chromosome. Because mice with either monosomy or tertiary trisomy for the 5(12) chromosomal region are viable, duplication/deficiency mapping is possible. Deficiency mapping was performed by mating iv/iv homozygotes and T31H heterozygotes. Two animals monosomic for distal mouse chromosome 12 were produced. One of the animals with cytogenetically confirmed monosomy for distal chromosome 12 exhibited situs inversus, indicating that the iv mutation is located at or distal to the T31H breakpoint. For duplication analysis, matings were initially carried out between iv/iv homozygotes and unbalanced T31H animals trisomic for distal chromosome 12. Cytogenetically verified tertiary trisomic progeny were identified and backcrossed with iv/iv homozygotes. The resulting trisomic progeny, 50% of which are expected to carry the iv mutation on both cytogenetically normal copies of chromosome 12, were scored for phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)

B–A chromosome mediated 3:1 disjunction in heterozygous reciprocal translocations of maize

In maize (Zea mays L.), meiotic segregation products of reciprocal translocations are well defined. The predictible meiotic behaviors and products generated by these interchanges allow them to be used as tools to gain basic information in cytogenetics, genetics, and plant breeding. In combining a classic reciprocal translocation with a single B–A chromosome from a tertiary trisomic B–A translocation stock, unique individuals with unusual chromosome karyotypes are generated. In cases where a B–A chromosome was present, the frequency of 3:1 disjunction within the ring of four was increased. In the case of T6–9(5454) + B–6Ld, cytological identification, via root-tip mitosis, was able to identify the specific tertiary trisomic products generated. These karyotypes are predictable and highly repeatable. Such karyotypes may have specific uses in chromosome mapping, chromosome dosage studies, or genetic or molecular investigations.Key words: reciprocal translocations, tertiary trisomes, interchange trisomes, B–A translocations, maize.

Generative transmission of the extra chromosome in a rye tertiary trisomic and its relation with inbreeding depression and pollen quality

Transmission of the extra (translocated) chromosome of tertiary trisomic T282W of rye (Secale cereale L.) upon seifing, through the male and/or the female, ranged from 0% to 36% in different inbred lines. Tetrasomics arising from simultaneous male and female transmission were not recovered and thus apparently not viable. Low seed weight, poor seed germination and a low transmission rate were correlated with low seed weight and reduced plant vigour. Inbreeding depression was concluded to affect transmission rate through its effect on the relative viability of trisomic seeds or seedlings.Male transmission in testcrosses with disomics averaged 7%, but varied between lines. Genetic factors were involved, but their expression remains uncertain. Pollen quality, as determined by a fluorescence reaction, was somewhat lower in trisomics than in disomics of the same genetic background and was not correlated with male transmission rate, which appears to be determined mainly by relative pollen-tube growth of euploid and aneuploid gametophytes. The results are discussed in relation to the use of tertiary trisomics in balanced chromosomal systems for hybrid breeding.