Translocation Homozygote Research Articles

P–576 Preimplantation genetic testing for consanguineous couple carrying an identical reciprocal translocation: clinical, ethical considerations and quandaries

Abstract Study question Which ethical and clinical aspects should be considered for preimplantation genetic testing PGT-SR strategy management for a consanguineous couple carrying the same reciprocal translocation? Summary answer PGT-SR management required specific probe designs to distinguish chromosomal patterns of balanced embryos, leading to complex transfer choices that required an adapted genetic counseling. What is known already Reciprocal translocation is a classic case in PGT-SR management, since all balanced embryos are transferable without distinguish between normal and balanced embryos. In accordance with the several recommendations, professionals calculated the reproductive risk related to the abnormalities and established an appropriate genetic counseling. However, an extreme case, such as the same reciprocal translocation carried by both members of a couple complicates PGT-SR management at all levels. Mainly, the genetics counseling around balanced embryo transfers. To date, only one study has reported a similar case, however, genetic counseling and the choice of embryos to be transferred have been poorly documented Study design, size, duration This study reports an extremely rare case of a couple (26-year-old woman and 29-year-old man) who was referred to our PGT center of the Montpellier University Hospital after 4 spontaneous miscarriages. The couple, first degree cousins in whom both partners are carrying the same reciprocal translocation 46,XX/XY,t(3;18) t(q26.1;q12.1). The patients were informed of the investigations and gave their consent before participation in the study. Participants/materials, setting, methods Peripheral blood of each member was investigated by FISH to caracterize chromosomal breakpoints. Secondly, a theoretical estimation of different segregation products to find a normal or balanced embryos were performed considering the extreme complexity of the case. Finally, an adapted PGT-SR probe strategy was conceived and proposed to a couple. Choices of balanced embryos to transfer were detailed to ensure that the patient is aware of risks and potential benefits. Main results and the role of chance In this particular case where both members of the couple are carrying the same reciprocal translocation, the chance of finding a normal or balanced embryo was further lowered 2% (4/196). It is estimated that the couple would produce 1 normal embryo and 15 balanced embryos. Diagnostic was possible on 16 biopsied embryos on day 3. Probe signal interpretations revealed four balanced embryos. Two embryos were proposed for a transferred on day 4. These balanced embryos had a different probe patterns, the first balanced embryo was normal and the second balanced embryo resulting from an adjacent–1 segregation mode presented an uniparental disomy (UPD). Limitations, reasons for caution ESHRE recommendations were established for common chromosomal rearrangements. In specific cases, limitations are strongly related to the complexity of the human genome. In this study, the choice of the embryos to be transferred depended entirely to our knowledge of phenotypic consequences of a homozygous gene alterations involved in chromosomal breakpoints. Wider implications of the findings: Professionals were confronted with requests to transfer balanced embryos with a partial/complete UPD or a balanced double translocation homozygote to improve the transfer rate from 3/196 of balanced combinations to 16/196. Dilemma between risks and benefits were considered for counseling to ensure an informed decision-making by patients. Trial registration number NA

Molecular and cytogenetic identification of Triticum aestivum-Leymus racemosus translocation line T6DL·7LrS

Leymus racemosus had a high resistant capacity to wheat scab (Fusarum head blight). The transfer of scab resistant gene from L. racemosus to Triticum aestivum is of great significance for broadening the germplasm of wheat resistance. To obtain Triticum aestivum-Leymus racemosus translocation line with scab resistance, we irradiated the pollen of T. aestivum-L. racemosus disomic addition line DA7Lr by ⁶⁰Co-γ-rays 1 200 R (100 R/min) prior to pollinating to emasculation T. aestivum cv. Chinese Spring. One plant with one translocation chromosome was detected in the M1 by GISH. The plant with one translocation chromosome was self-pollinated, and at meiotic metaphase I its progenies with two translocation chromosomes were analyzed for chromosome pairing behavior in their pollen mother cells (PMCs). One rod bivalent was observed at meiotic metaphase I, indicating that the plant with two translocation chromosomes was one translocation homozygote. Sequential GISH-FISH analysis, using Oligo-pAs1-2 and Oligo-pSc119.2-2 as probe, translocation line was confirmed as T6DL·7LrS. The translocation line had higher resistance to wheat scab and feasibility to be used as a new source in wheat breeding resistant to scab disease.

Attempts to Transfer Russian Wheat Aphid Resistance from a Rye Chromosome in Russian Triticales to Wheat

The Russian wheat aphid (Diuraphis noxia Mordvilko) is a serious pest of wheat (Triticum aestivum L.). To extend the range of genetic variation of resistance, attempts were undertaken to transfer near‐immunity to RWA into wheat from two Russian triticales (X. Triticosecale Wittmack) PI 386146 and PI 386156 by irradiation and by induced homologous recombination. The rye genome in the triticale lines was derived from Secale montanum Guss. Tests of resistance in early backcrosses to wheat indicated that the near‐immunity of the triticale lines was controlled by at least two loci, one of which was located on rye chromosome arm 4RLmon Centric wheat‐rye translocation 7DS.4RLmon that appeared to be compensating, was produced. To further reduce the amount of rye chromatin present, its long arm was induced to recombine with wheat chromosomes by the removal of the Ph1 locus. Among 3563 progeny screened, only two wheat‐rye recombinant chromosomes were recovered. Both appeared to be non‐compensating and were involved in multivalents in meiosis. Irradiation of PI 386156 followed by crosses and backcrosses to wheat with several generations of selection for resistance resulted in a wheat line that was found to be a disomic addition of chromosome 4Rmon–centric translocation homozygote of rye chromosome tentatively identified as 5Rmon With only one locus for resistance from the original triticale parents, the addition line of 4Rmon, centric translocation line 7DS.4RLmon and recombinant lines of 4RLmon had only moderate level of resistance to RWA. The study demonstrates that transfers of alien variation into wheat may be severely complicated by unclear genetics of the target traits, low levels of homology, and structural differences between the donor and recipient chromosomes.

Genetic diversity among Plantagos. XXXIII

Summary Following irradiation of dried seeds of Plantago ovata with gamma rays, a plant was recovered which had 8 chromosomes. Of 8 chromosomes, 2 chromosomes were distinct morphologically Morphometery and synaptic behaviour of the chromosomes suggest that the variant is a translocation heterozygote, having 2 chromosomes involed. in interchange. This variant was selfed and crossed in various directions. A translocation homozygote was isolated in the selfed progeny. Chromosome complement, nature and meiotic behaviour of both translocation hetero- and homozygote have been discussed.

AN ALTERNATIVE METHOD FOR ISOLATING HOMOZYGOTES OF AUTOSOMAL TRANSLOCATIONS IN THE MOSQUITO CULEX TARSALIS

An alternative pseudolinkage procedure for isolating homozygotes of autosomal translocations has been developed with the mosquito Culex tarsalis (Coquillet). The first step was to induce a translocation heterozygote in a population that was marked with recessive mutants. Interbred translocation heterozygotes produced translocation homozygotes that were phenotypically different from their translocation heterozygote and normal siblings. Thus, a translocation homozygote line of this species was selected and established in shorter time and with less effort than by prior pseudolinkage procedure.

Laboratory evalution of a translocation double heterozygote for genetic control of Aedes aegypti

Two pure translocation homozygote stocks, T1/T1 and T3/T3, were used to produce a double translocation heterozygote system designated T1/T3, employing T1/T1 as the male and T3/T3 as the female parent. The double heterozygote showed 73 % sterility when mated to wild females. Tests on mating competitiveness, recombination frequency in the differential segment, insemination rate and inheritance of sterility after release, for four generations in laboratory cages, have been carried out to evaluate the efficiency of this strain as an agent for a population control programme.

The consequences of an unusual Robertsonian translocation in celery (Apium graveolens var dulce)

A Robertsonian translocation found in a cultivar of celery is described which is unusual because half the small product of the exchange survives as a telocentric chromosome. The change has no drastic effect on the overall fitness of the translocation homozygote. The consequences of such a change for karyotype evolution are shown to be, karyotype asymmetry, the possible genesis of B-chromosomes and the possibility of a chromosome change becoming established even though it has no adaptive value.

Field Trials with a Translocation Homozygote in Aedes aegypti for Population Replacement1

Translocation homozygote strains of the yellowfever mosquito carrying several genetic markers were released in villages near Mombasa on the Kenya coast in an attempt to replace the indigenous populations by the introduced strains. A translocation strain marked with red eye was recovered in very low numbers after releases. However, when a strain marked with wild-type eye color was released, it readily entered houses and laid eggs in ovitraps. Translocation progeny were rarely obtained from natural breeding containers and none of the translocation strains became established in the field. Fitness studies conducted in the field and the laboratory showed that the translocation strains were deficient in fertility, larval development time, larval and adult survival, and mating competitiveness. Experiments also demonstrated that, when a choice was offered, native females laid 90% of their eggs in natural breeding sites while females carrying the translocation preferred ovitraps, laying 62% of their eggs in these sampling containers.

Interference by recessive lethals in the re-isolation of a translocation homozygote inAedes aegypti

A reciprocal translocation between chromosome 2 and 3, designated T2, was viable when homozygous in the ROCK strain ofAedes aegypti. It was backcrossed five times with Delhi wild type material. Despite intensive efforts it was not possible to re-isolate it as a homozygote, indicating that a factor in the Delhi background interacted with the translocation and caused recessive lethality. In certain families inbreeding without the production of genetically marked non-translocation homozygotes suggested that a translocation homozygote line had been isolated but, when outcrossed, all the individuals were found to be translocation heterozygotes. It was shown that a balanced lethal system existed which maintained permanent translocation heterozygosity in this line.

Selection on the fertility of translocation heterozygotes inDrosophila melanogaster. 1. The extent of the changes produced by selection

As part of a study on the suitability of translocations for insect pest control, artificial selection was applied for either higher or lower egg hatchability in each of the reciprocal matings between a translocation heterozygote and a translocation homozygote. In each of four selection lines, there was response to selection but, after 3–4 generations, limits were reached beyond which further selection gave no response. On reversing the directions of selection, the high and low lines rapidly exchanged their levels of egg hatchability and then established new plateaux. Relaxation of selection caused convergence towards the original unselected level. It is concluded that individuals with extremely high or low fertility were disfavoured by natural selection. Populations initiated from two different translocation homozygotes formed a stable polymorphism and after propagation in bottles for 10 generations, small increases were found in the fertility of the double translocation heterozygotes compared with the same genotype newly produced from unselected homozygote stocks. It is concluded that, under the conditions of the bottle cultures, natural selection favoured increase in fertility of the double heterozygotes.

Radiation induced semi-sterility for genetic control purposes in the onion flyHylemya antiqua (Meigen)

In the preliminary stages of a study into the use of translocations for genetic control of the onion flyHylemya antiqua (Meigen), irradiations were carried out in order to obtain chromosomal rearrangements. Several irradiation experiments, with X-rays or fast neutrons, were carried out on pupae and adults of both sexes at substerilizing doses below 3.0 krad, to establish a favourable way of induction.Because no visible markers are available for the genetic screening of induced rearrangements, and the reciprocal translocations or inversions in demand express themselves in the heterozygous condition by reduced fertility, a total of 234 F1 individuals of both sexes were checked for reduced fertility. 50 F1 individuals were suspected of carrying a translocation or inversion when they produced an egg hatch of between 30 and 60% (semi-sterility).This category was passed for cytogenetic analysis. In the progeny of 25 suspect F1 individuals, 9 different rearrangements were established, of which 7 were translocations. This means a yield of 4% for all the tested F1 After a discussion of the normal karyotype, some of the observed rearrangements are described.Irradiation of males with 1.0 krad of X-rays is advised for the production of semi-sterile stocks carrying translocations. Fast neutrons were not found to be better than X-rays. At doses higher than 1.0 krad complex rearrangements and/or fragments were observed.A translocation homozygote could be isolated in the case of an X-autosomal translocation, and this stock will be used for further genetic control purposes.

House fly genetics. II. Isolation of a heat-sensitive translocation homozygote.

Journal Article House Fly Genetics: II. Isolation of a heat-sensitive translocation homozygote Get access IAN C. MCDONALD, IAN C. MCDONALD Radiation Biology and Insect Genetics Section of the Metabolism and Radiation Research Laboratory, U.S. Department of AgricultureFargo, North Dakota 58102 Search for other works by this author on: Oxford Academic PubMed Google Scholar DELORES E. OVERLAND DELORES E. OVERLAND Radiation Biology and Insect Genetics Section of the Metabolism and Radiation Research Laboratory, U.S. Department of AgricultureFargo, North Dakota 58102 Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Heredity, Volume 64, Issue 5, September 1973, Pages 253–256, https://doi.org/10.1093/oxfordjournals.jhered.a108406 Published: 01 September 1973

Controlled crosses and cage experiments with a translocation in Drosophila

Predictions for the use of autosomal translocations for pest control have been made on the assumptions that translocation heterozygotes are semi-sterile and translocation homozygotes are fully fertile and have viabilities which are either equal to or slightly less than that of the wild type. These parameters were assessed in controlled crosses using a translocation in Drosophila and they showed good agreement with expectation. It was expected that in a mixed population of such translocations and wild types, the karyotype at the higher frequency would be favoured by selection. Two cage experiments were initiated with mixed populations of translocation homozygotes and wild types at a frequency of 9:1 in favour of the translocation. Contrary to expectation, the translocation was eliminated from both populations. During this process, there was a reduction in population fertility. Computer studies showed that the results were consistent with a reduction in fitness of the translocation homozygote to about 0.5, i.e. about the same as the semi-sterile heterozygote, so that negative heterosis did not exist and hence frequency dependent selection could not occur.

A possible genetic method for the control of insect pests, with special reference to tsetse flies (Glossina spp.).

The use of chromosome translocations for the control of pests, with particular reference toGlossina, is proposed. A translocation arises if two non-homologous chromosomes in the same cell undergo breakage and the fragments re-join with the wrong partners. At meiosis in an individual heterozygous for a translocation, gamete nuclei with several different combinations of chromosomes are produced. Some of these are diploid for one part and lack completely another part of the normal chromosome set; when such unbalanced gametes fertilise normal gametes inviable embryos are produced. It has been found in a number of organisms that about half the gametes of translocation heterozygotes are of the unbalanced type and such heterozygotes are described as semi-sterile. If an individual inherits the same translocation from both parents it is described as a translocation homozygote; this is often inviable but, if not, its fertility is usually normal.Adult males ofG. austeniNewst. have been irradiated and each of their progeny are being screened for the occurrence of semi-sterility. Any individuals found to be semi-sterile would probably be translocation heterozygotes and their progeny will be inbred to try to produce a viable stock, homozygous for a translocation. If this can be done, large numbers of such translocation homozygotes could be reared and released into a wild population, where matings with wild types would produce heterozygotes, and hence a reduction in the fertility of the population.Using simple assumptions, the effects of releasing translocation homozygotes were computed. Provided the numbers released were such that the translocation frequency approached the optimum value of 50 per cent., the reduction in population fertility would be prolonged for many generations after the releases had finished. It is shown that it would be more efficient to release the translocation homozygotes at successive generations rather than all at once and that the homozygotes released could with advantage be of both sexes. For this reason, and because of the prolonged effect of releases of translocations, it is concluded that the number of individuals that would have to be reared to achieve a given result by the translocation method might be considerably less than if the sterile-male method was used. However, the reduction in population fertility at each generation that can be achieved with the translocation method is limited, and the method would therefore be ineffective against populations whose size was strongly buffered by density-dependent factors.

SPONTANEOUS MEIOTIC CHROMOSOME BREAKAGE IN NATURAL POPULATIONS OF PAEONIA CALIFORNICA

THE AMERICAN SPECIES of Paeonia, P. californica and P. brown,ii, show in natural populations a high degree of meiotic irregularity. They have evolved a cytogenetic system of which the most prominent feature is permanent translocation heterozygosity, comparable to that of Oenothera (Stebbins and Ellerton, 1939; J. Walters, 1942). They show in addition a great deal of inversion hybridity, revealed by the familiar bridge-and-fragment configurations of heterozygous paracentric inversions, and by the presence of heteromorphic chromosome pairs which have been interpreted as the result of heterozygosity for pericentric inversions (J. Walters, 1952). In the course of the previous studies of structural hybridity, occasional cells were noted which showed fragmentation in meiosis occurring in various degrees. A range of breakage has been observed from cells with a single fragment to cells in which not a single intact chromosome is present. As spontaneous fragmentation in meiosis is not common, and has not previously been reported to occur in a structural hybrid, a study was undertaken to determine the extent to which fragmentation occurs in P. californica, and whether any relationship can be shown with the other kinds of meiotic irregularity. The results of this study form the subject of the present paper. MATERIALS AND METHODS.-Flower buds of P. californica were collected in the field, fixed in Bradley's (1948) fixative, and stored in the fixative under refrigeration. The studies and photomicrographs were made from temporary and permanent iron-acetocarmine smears. In order to investigate the relationship between the extent of translocation heterozygosity and that of breakage, the plants selected for study included four pairing types: the translocation homozygote, with 511; an intermediate translocation heterozygote, with 06+2112; and two types of extreme heterozygote, with (I10 and 06 +04 respectively. In addition to the material collected in the wild, fixations were made from two plants that had been transplanted several years earlier into the Santa Barbara Botanic Garden, to observe possible effects on breakage of growing a plant in other than its native habitat. In five plants, four stages of meiosis (metaphase and anaphase of the first and second divisions) were studied, to