TRISOMICS IN SOLANUM CHACOENSE: FERTILITY AND CYTOLOGY

Twenty trisomic plants found in the progeny 3x x 2x crosses in Solatium chacoense and their F₁ trisomies obtained by 2x + 1 X 2x crosses were studied with respect to their fertility and cytology. The female transmission of the extra chromosome in the trisomics varied from 2 to 60 %. The transmission frequencies of F₁ trisomies were similar to their parent trisomies in most of the lines. The transmission through the pollen ranged from 0 to 20 %. Female and male fertility of the parent trisomies was high. They produced an average of 37 seeds per pollination as the female or as the male parent. The F₁ trisomies produced about half the seed set of their parent trisomies. The extra chromosomes of six trisomies were identified by pachytene analysis. They were isochromosomes for the long arms of chromosomes I, IV and IX and the short arms of IV, IX and XII. Chromosome morphology of the extra chromosomes in pachytene stage was described. A chromosome association of 12 II + 1 I was found in 66 % of the cells at MI. About 29 % of the cells had one trivalent and 5 % had three or five univalents. The frequency of trivalent formation was not affected by the length of the extra chromosome. The possibility of univalent shift in secondary trisomies was discussed.     

Mosaic trisomies in human spontaneous abortions

Summary Data from a cytogenetic survey of spontaneous abortions were examined to determine the incidence and origin of mosaic trisomies in this population. The overall frequency of mosaicism among trisomies was approximately 5%, but the level of mosaicism varied significantly among trisomies, being much higher for the nonacrocentric than for the acrocentric trisomies. Evidence from chromosome heteromorphism analysis suggests that the extra chromosome in mosaic trisomies usually has a meiotic origin.This work was supported by Grant HD 07879 and Fellowship HD 05576 from the National Institutes of Health     

Genetic diversity among Plantagos

Summary In the progenies of the crosses between disomics and trisomies, two plants were isolated which carried an extra chromosome that was unlike any in the standard complement. The plants were not alike; while one carried a metacentric, the other had a telocentric extra chromosome. Their detailed structure and possible modes of origin are discussed.     

On the deletion 4p16 Wolf-Hirschhorn syndrome.

Two girls (aged 46 and 5 months) and one boy aged 5 months) were studied and found to have the Wolf-Hirschhorn syndrome. Chromosomal complement in all three cases implicated the deletion of the 4p16 band ; in two of them an extra segment of autosomal material was found to be translocated to 4p. Parents' karyotypes were normal. It is concluded that the expression of the 4p16 monosomy is stronger than that of some simultaneous partial trisomies.     

Origin of trisomies in human spontaneous abortions

Summary Chromosome heteromorphisms of 34 trisomic abortuses and their parents were compared to determine the origin of the extra chromosome. Fourteen of the trisomies were maternal in origin, ten resulting from a first-meiotic-division error and four from either first- or second-meiotic-division errors. No paternally derived trisomy was identified.     

Genome-wide detection of additional fetal chromosomal abnormalities by cell-free DNA testing of 15,626 consecutive pregnant women

Cell-free DNA(cfDNA) testing for common fetal trisomies(T21, T18, T13) is highly effective. However, the usefulness of cfDNA testing in detecting other chromosomal abnormalities is unclear. We evaluated the performance of cfDNA testing for genome-wide abnormalities, and analyzed the incremental yield by reporting extra abnormalities. We performed genome-wide cfDNA testing in 15,626 consecutive pregnancies prospectively enrolled in this study. cfDNA testing results were reported and counseling was given depending on the presence of extra chromosomal abnormalities. cfDNA testing identified 190 cases(1.2%)of chromosomal abnormalities including 100 common trisomies and 90 additional abnormalities. By expanding the cfDNA reporting range to genome-wide abnormalities, the false positive rate increased to 0.39%(P0.001) and positive predictive value(PPV) was reduced to 65.58%(P=0.42). However, the detection yield increased from 0.44% to 0.65%(P=0.014), and cfDNA testing detected 38.61%(39/101) additional abnormalities with no ultrasound and biochemical screening findings. cfDNA testing outperformed biochemical screening by showing 60 times higher true positive rate and fewer false negative results.Genome-wide cfDNA testing significantly increased the diagnostic yield by detecting extra abnormalities, especially those without diagnostic indications. Genome-wide cfDNA testing has fewer false positive and false negative results compared with biochemical screening.     

Unbalanced Robertsonian translocations associated with Down's syndrome or Patau's syndrome: Chromosome subtype,proportion inherited,mutation rates,and sex ratio

Summary Summary data are presented on 168 D/21 and 131 G/21 translocation trisomies reported to the New York State Chromosome Registry. By combining these data with others from the literature it is estimated that about 59% of D/21 cases are the result of mutation in the parental generation; the rest are translocations inherited from parental carriers (39% maternal, 3% paternal). The proportion of mutants is about 10% greater for 14/21 cases and significant lower for 13/21 cases. Of G/21 cases 93% are mutant, about 6% of maternal origin, and 1% of paternal origin. All the mutant cases involve 21/21 rearrangements. Estimated mutation rates per 10⁵ gametes for translocation trisomies in affected livebirths are 0.1 for 21/13, 0.5 to 0.9 for 21/14, and 1.1 to 1.4 for 21/21. The rates for 21/15 and 21/22 translocation trisomies are probably all conservatively less than 0.1 per 10⁵ gametes. Of interchange trisomy Patau's syndrome, about 60% of cases are mutant; the rest are translocations inherited from a parental carrier (about 25% for 13/13 cases and about 45% for 13/14 cases. The estimated mutation rates for 13/13 and 13/14 interchange trisomies are each about 0.5 per 10⁵ gametes; the rate for 13/15 interchange trisomies is less than 0.1 per 10⁵ gametes. A male excess is observed for D/21 (sex ratio=1.70), and G/21 (sex ratio=1.38) interchange Down's syndrome, and a female excess for D/13 interchange Patau's syndrome (sex ratio =0.77), trends similar to those seen in the respective 47, trisomies associated with these phenotypes.     

Production and identification of primary trisomics in diploid Agropyron cristatum (crested wheatgrass).

Six of the seven possible primary trisomics in Agropyron cristatum were produced. Based on morphology, arm length ratios, and C-banding patterns, they were identified as primary trisomics for chromosomes A, B, C, D, E, and G. Agropyron cristatum is one of several species constituting the crested wheatgrass complex. All species in this complex contain one basic genome (P). A study was conducted to produce and identify a primary trisomic series that will be used to map genes to individual chromosomes. A population of 157 plants were generated by crossing autotriploids (PPP) with diploid (PP) A. cristatum: 58 were diploid (2n = 14), 76 were primary trisomies (2n = 15), 17 were double trisomic (2n = 16), 4 were triple trisomics (2n = 14 + 3), 1 was telocentric trisomic (2n = 14 + 1 telo), and 1 was tetratrisomic (2n = 14 + 4). Karyotype analysis of acetoorcein-stained chromosomes was carried out using the CHROMPAC III computer program; for analysis of C-banded karyotypes, the computer imaging analysis program PCAS (Plant Chromosome Analysis System) was used to identify the primary trisomics. Of the 47 primary trisomics analyzed, 21 plants had one extra satellited chromosome E, 18 with the satellited D chromosome, 3 each for chromosomes B and G, and 1 each for chromosomes C and A. Chromosome pairing was studied in trisomies B, D, E, and G. Trisomics for chromosomes B and G were similar in their mieotic behavior. Each had a trivalent frequency of about 60% and pollen stainability of less than 40%. Trisomics for chromosomes D and E had a trivalent frequency of about 30% and pollen stainability of over 70%.     

Anatomic and chromosomal anomalies in 639 spontaneous abortuses

Summary A total of 639 spontaneous abortuses collected in a maternity hospital were set up in culture. This sample included 565 unselected consecutive abortuses and 74 selected abortuses ascertained by morphology and/or clinical history. Among these, 339 were incomplete specimens with no recovered embryo or fetus, 110 were anatomically apparently normal and 190 were grossly abnormal. In the unselected series, 565 specimens were cultured and 402 were karyotyped; 215 (53.5%) were chromosomally abnormal. In the selected series, 74 specimens were set up in culture and 45 were karyotyped; 26 (57.7%) had an abnormal karyotype. In all, successful karyotyping was done on 447 abortuses (70%), of which 339 were studied with banding. One or more major chromosome abnormalities were detected in 241 (54%) of the karyotyped cases, 230 of which were numerical anomalies and 11 structural anomalies. Numerical anomalies included primary autosomal trisomies (31% of the total karyotyped), 45,X (10%), triploidy (6.5%), and tetraploidy (1.8%). Of the 22 types of autosomal trisomies possible, all except those for 1, 5, 17, and 19 were identified. An abortus with a 49,XX,+2,+5,+8 karyotype was detected. The excess autosomal material present in the triple trisomic abortus corresponded to 10% of the haploid autosomal complement. Of the 11 abortuses with structural abnormalities, seven were inherited while the other four were sporadic. The survival rate of 45,X conceptuses was estimated to be one in 300.     

Trisomy: Chromosome competition or maternal strategy?: Increase of trisomy incidence with increasing maternal age does not result from competition between chromosomes

Axelrod and Hamilton (Science 211:1390, 1981) suggested that trisomies may result from an end-game strategy between chromosomes competing to get on the gamete as the mother approaches menopause. We tested this hypothesis by reviewing studies of the parental origin of the extra chromosome in trisomy 21 births. These data show that there is no significant rise in trisomy 21 conceptions as the mother ages. The increase in trisomies with maternal age results not from an increase in nondisjunctions, but from a decrease in rejection of trisomy zygotes, which may be adaptive for the mother towards the end of her reproductive life. This decreasing rate of rejection may result from the changing inclusive benefits of two maternal strategies as menopause approaches.     

TRIVALENT FORMATION IN MULTIPLE TRISOMICS OF CLARKIA UNGUICULATA

Vasek, F. C. (U. California, Riverside.) Trivalent formation in multiple trisomics of Clarkia unguiculata. Amer. Jour. Bot. 50(3): 244–247. 1963.—A series of multiple trisomics, ranging from 2n + 1 to 2m + 7, was scored for univalents and trivalents at first metaphase. The mean number of trivalents per cell per extra chromosome was 0.43, 0.46, 0.46, 0.56, 0.54, 0.55 and 0.59 for plants with 1, 2, 3, 4, 5, 6 and 7 extra chromosomes respectively. These trivalent frequencies are interpreted to fall into 2 classes, indicating that the cytological differences between triploids and single trisomies may be based on a threshold effect. The results are compared with available data from other genera, and it is suggested that the observed increase in trivalent formation per extra chromosome may be associated with an increase in chiasma frequency.     

Origin of acrocentric trisomies in spontaneous abortuses

Summary A total of 33 spontaneous abortuses with various acrocentric trisomies were studied for the origin of the extra chromosomes using Q- and R-band polymorphisms as markers. Eleven trisomic abortuses were informative: nine trisomic abortuses (one with trisomy 13, three with trisomy 21, and five with trisomy 22 including one with a 46,XX/47,XX,+22 mosaicism) originated at maternal first meiosis; a 21-trisomic abortus resulted from an error at maternal second meiosis (or first mitosis); and a 13-trisomic abortus was of maternal first or second meiotic origin. The abortus with mosaic trisomy 22 started as a 22-trisomic zygote resulting from an error at maternal first meiosis, followed by a mitotic (in vivo or in vitro) loss of the paternally derived chromosome 22.     

A systematic cytogenetic study of a population of 1170 mentally retarded and/or behaviourly disturbed patients including fragile X-screening. The Hondsberg experience

A cytogenetic study was performed in a population of 1170 mentally retarded and/or behaviourly disturbed patients of the Hondsberg Institute in the south of the Netherlands. The cytogenetic data are presented and discussed. In all patients chromosomal evaluation was performed with Giemsa-banding and Quinacrine fluorescence, and additional banding techniques were performed whenever they were necessary to clarify the chromosomal abnormality. A fragile X screening with M199 cultures was performed in 311 males. In 22.1% of the patients a chromosomal basis was found for their developmental retardation: 14.3% Down syndrome patients, 6.1% other chromosomal abnormalities (mainly partial autosomal trisomies and monosomies and sex-chromosome abnormalities). In 24 males, through 21 index patients, a positive fragile X screening was found, i.e. 6.7% of the screened population and 1.8% of the total population. These results indicate that the diagnostic contribution of the fragile X screening is numerically of equal importance as are advanced chromosome banding techniques, and its contribution to the diagnosis of fragile X syndrome in one index male patient in general leads to the detection of several female relatives at risk to be carrier of this X-linked recessively inherited condition. The causal relationship between the occurrence of mental retardation and chromosomal aberration in genera i.e. autosomal trisomies, partial autosomal trisomies and monosomies, and Xq27-28 fragility is well established and is, to some extent, easy to understand. Whether carriers of other chromosomal rearrangements, mainly of balanced reciprocal and Robertsonian translocations, small extra chromosomes, paracentric inversions and chromosomal variants, have increased risk for mental handicap and/or congenital malformations in their progeny, remains unclear at the present time. Some of these residual problems and questions are discussed in the perspective of their importance for genetic counseling. Detailed data will be presented about the mental development and psychological profile of patients with these different types of chromosomal abnormalities and rearrangements.     

Telomere lengths at birth in trisomies 18 and 21 measured by Q-FISH

Trisomies 18 and 21 are genetic disorders in which cells possess an extra copy of each of the relevant chromosomes. Individuals with these disorders who survive birth generally have a shortened life expectancy. As telomeres are known to play an important role in the maintenance of genomic integrity by protecting the chromosomal ends, we conducted a study to determine whether there are differences in telomere length at birth between individuals with trisomy and diploidy, and between trisomic chromosomes and normal chromosomes. We examined samples of peripheral blood lymphocytes (PBLs) from 31 live neonates (diploidy: 10, trisomy 18: 10, trisomy 21: 11) and estimated the telomere length of each chromosome arm using Q-FISH. We observed that the telomeres of trisomic chromosomes were neither shorter nor longer than the mean telomere length of chromosomes as a whole among subjects with trisomies 18 and 21 (intra-cell comparison), and we were unable to conclude that there were differences in telomere length between 18 trisomy and diploid subjects, or between 21 trisomy and diploid subjects (inter-individual comparison). Although it has been reported that telomeres are shorter in older individuals with trisomy 21 and show accelerated telomere shortening with age, our data suggest that patients with trisomies 18 and 21 may have comparably sized telomeres. Therefore, it would be advisable for them to avoid lifestyle habits and characteristics such as obesity, cigarette smoking, chronic stress, and alcohol intake, which lead to marked telomere shortening.     

Cytogenetic and histologic analyses of spontaneous abortions

Summary In a study of spontaneous abortions the correlations between karyotype (166 cases), anamnestic data, and macroscopic and histologic findings in placentas (107 cases) and embryos (73 cases) were analyzed. The main results were: 1. The rate of chromosomal aberrations was 39%. Trisomies predominated (60%), followed by monosomy X (20%), triploidies (14%), and structural aberrations (6%). 2. In trisomies a clear prevalence of female sex constitution (2:1) was observed. In normal karyotypes a slight prevalence of females was seen (1.2:1). 3. With increasing maternal age, more trisomies were found in the abortions. 4. Women whose index abortion had a normal karyotype had a history of fewer births but more abortions. 5. Trisomies of acrocentric chromosomes were mainly chorionic sacs with an embryo, while trisomies of the other autosomes resulted in intact empty sacs. 6. The average developmental stage of the embryos was 5 weeks, with a mean gestational age of 14 weeks. Gross malformations were found in 58% of the embryos.     

Trisomy 4q syndrome: presentation of a new case and review of the literature

We describe the 11th case of a de novo partial trisomy of the long arm of chromosome 4, with the extra segment spanning from 4q27 to 4q35. The aberration resulted from an unbalanced translocation of material from 4q to the short arm of chromosome 7, as evident from fluorescent in situ hybridization. Microsatellite analysis revealed the extra material to originate from the father. The karyotype was interpreted as 46,XX,der(7)t(4;7)(q27;p22). The patient is a 13-year-old girl with severe mental retardation, growth retardation, hearing impairment as well as minor foot, thumb and facial anomalies. Although the extent of the aberration varies between the reported patients, there are nevertheless features in common, suggestive of a trisomy 4q syndrome. The clinical findings most frequently reported are: mental retardation, seizures, microcephaly, hearing impairment and growth retardation, as well as epicanthic folds, high/broad/depressed nasal bridge, malformed ears, tooth and thumb anomalies. Almost the entire long arm of chromosome 4, except band q11, has been involved in trisomies/duplications, but 4q27 and 4q31 seem to be preferentially engaged in the trisomy 4q syndrome.     

Trisomy recurrence: a reconsideration based on North American data

Few reliable data exist concerning the recurrence risk for individual trisomies or the risk for recurrence of trisomy for a different chromosome. We collected records from two sources: (1) prenatal diagnoses performed at the Hopital Sainte-Justine in Montreal and (2) karyotype analyses performed at Genzyme. Using the standardized morbidity ratio (SMR), we compared the observed number of trisomies at prenatal diagnosis with the expected numbers, given maternal age-specific rates (by single year). SMRs were calculated both for recurrence of the same trisomy (homotrisomy) and of a different trisomy (heterotrisomy). After all cases with an index trisomy 21 were combined, the SMR for homotrisomy was 2.4 (90% CI 1.6-3.4; P=.0005). For women with both the index trisomy and subsequent prenatal diagnosis at age <30 years, the SMR was 8.0; it was 2.1 for women with both pregnancies at age >/=30 years. For the other index viable trisomies (13, 18, XXX, and XXY) combined, the SMR for homotrisomy was 2.5 (90% CI 0.7-8.0). For heterotrisomy, the SMR after an index trisomy 21 was 2.3 (90% CI 1.5-3.8, P=.0007); the SMR did not vary with maternal age at the first trisomy. When all cases with index viable trisomies were combined, the SMR for heterotrisomy was 1.6 (90% CI 1.1-2.4; P=.04). For prenatal diagnoses following a nonviable trisomy diagnosed in a spontaneous abortion (from Genzyme data only), the SMR for a viable trisomy was 1.8 (90% CI 1.1-3.0; P=.04). The significantly increased risk for heterotrisomy supports the hypothesis that some women have a risk for nondisjunction higher than do others of the same age.     

Nondisjunction of human acrocentric chromosomes: studies of 432 trisomic fetuses and liveborns

The present report summarizes molecular studies on the parent and meiotic stage of origin of the additional chromosome in 432 fetuses or liveborns with an additional chromosome 13, 14, 15, 21, or 22. Our studies suggest that there is little variation in the origin of nondisjunction among the five acrocentric trisomies and that there is no association between the origin of nondisjunction and the likelihood of survival to term of the trisomic conceptus. The proportion of cases of paternal origin was similar among the five trisomies: 12% for trisomy 13, 17% for trisomy 14, 12% for trisomy 15, 9% for trisomy 21, and 11% for trisomy 22. The stage of nondisjunction was also similar among the five trisomies, with the majority of cases of maternal origin being due to nondisjunction at meiosis I, whereas for paternally derived cases, nondisjuction occurred primarily at meiosis II.     

Trisomy and triploidy are sources of embryo mortality in the zebra finch

Hatching failure is a surprisingly common phenomenon given that natural selection constantly works against it. In birds, an average of about 10 per cent of eggs across species fail to hatch, often owing to the death of embryos. While embryo mortality owing to inbreeding is both well-documented and evolutionarily plausible, this is not true for other sources of mortality. In fact, the basis for hatching failure in natural populations remains largely unexplained. Here, we demonstrate that embryo mortality in captive zebra finches (Taeniopygia guttata) follows from chromosomal aneuploidy or polyploidy. As part of microsatellite genotyping of a captive breeding population, we found 12 individuals (3.6%) with three alleles among 331 embryos that had died during development, while there were no such cases observed among 1210 adult birds. Subsequent genotyping of 1920 single nucleotide polymorphism markers distributed across the genome in birds with three alleles at microsatellite loci, and in greater than 1000 normal birds, revealed that the aberrant karyotypes involved cases of both trisomies and triploidy. Cases of both maternally and paternally inherited trisomies resulted from non-disjunction during meiosis. Maternally inherited cases of triploidy were attributable to failure of meiosis leading to diploid eggs, while paternally inherited triploidy could have arisen either from diploid sperm or from dispermy. Our initial microsatellite screening set only had the power to detect less than 10 per cent of trisomies and by extrapolation, our data therefore tentatively suggest that trisomy might be a major cause of embryo mortality in zebra finches.     

Double trisomy in spontaneous abortions

Cytogenetic data on products of conception from spontaneous abortions studied over a 10-year period have been reviewed for double trisomies. A total of 3034 spontaneous abortions were karyotyped between 1986 and 1997. Twenty-two cases with double trisomy, one case with triple trisomy, and a case with a trisomy and monosomy were found. The tissues studied were mostly sac, villi, or placenta. The gestational age ranged from 6 to 11 weeks and the mean age was 8.2 ± 1.7 (SD) weeks. The mean maternal age in years was 35.9 ± 5.3. Of the twenty-two cases, four were mosaics. All but two of the cases involved autosomal aneuploidies. The double trisomies included chromosomes 2, 4, 5, 7, 8, 12, 13, 14, 15, 16, 17, 18, 20, 21, and 22. The chromosomes that were trisomic in more than one double trisomy case were numbers 16 (8 cases), 8 (5 cases), 15 (4 cases), 2, 13, and 21 (3 cases each), and 5, 7, 14, 18, 20, 22, and X (2 cases). The triple trisomy involved chromosomes 18, 21, and X. The monosomy and trisomy case was a mosaic, with a monosomy 21 in all cells and some cells also with a trisomy 5. The double trisomies cited for the first time in this study were 4/13, 5/16, 8/14, 8/15, 14/21, 15/20, and 7/12. The pooled mean maternal age for double trisomy cases (34.1 ± 5.7 years) was higher than that for single trisomy cases (31 ± 6.1 years). The difference was statistically significant at P = < 0.001. The pooled mean gestational age of spontaneous abortions was lower for double trisomy (8.7 ± 2.2 weeks) than for reported single trisomy cases (10.1 ± 2.9 weeks). This difference is also statistically significant at P = < 0.001. The sex ratio among double trisomies was 15 females to 13 males. This difference was not statistically significant from the expected 1 : 1. Received: 27 June 1997 / Accepted: 4 September 1997