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T J Hassold

Publications and source records attributed to T J Hassold.

53 records · Page 3Linked to original sources
PubMed1991

Molecular studies of non-disjunction in trisomy 16.

The origin of the additional chromosome in 26 trisomy 16 spontaneous abortions was studied using DNA probes for chromosome 16, including a probe for centromeric alpha sequences. We were able to determine the parent and meiotic stage of origin of trisomy in 22 cases, with all being attributable to maternal meiosis I non-disjunction. Furthermore, in each of the remaining four cases the results were compatible with this origin. Thus, it is likely that the high incidence of trisomy 16 results from an abnormal process acting at maternal meiosis I which more frequently involves chromosome 16 than other similar sized chromosomes. In studies of recombination, we found little evidence for an association between reduced or absent recombination and chromosome 16 non-disjunction; however, we were unable to rule out an effect of hyperrecombination.

Cells, Cultured↗
PubMed1991

XY chromosome nondisjunction in man is associated with diminished recombination in the pseudoautosomal region.

To assess the possible association between aberrant recombination and XY chromosome nondisjunction, we compared pseudoautosomal region recombination rates in male meiosis resulting in 47,XXY offspring with those resulting in 46,XY and 46,XX offspring. Forty-one paternally derived 47,XXYs and their parents were tested at six polymorphic loci spanning the pseudoautosomal region. We were able to detect crossing-over in only six of 39 cases informative for the telomeric DXYS14/DXYS20 locus. Subsequently, we used the data to generate a genetic linkage map of the pseudoautosomal region and found it to be significantly shorter than the normal male map of the region. From these analyses we conclude that most paternally derived 47,XXYs result from meiosis in which the X and Y chromosomes did not recombine.

Chromosome Mapping↗
PubMed1990

The parental origin of the extra X chromosome in 47,XXX females.

We used X-linked DNA polymorphisms to study the parental origin of X chromosome nondisjunction in 28 47,XXX live-born females. Errors in oogenesis accounted for 26 of the cases, with the majority of these being attributable to an error at meiosis I. We observed an association between advanced parental age and meiosis I nondisjunction--but not meiosis II nondisjunction--in the maternally derived cases. In studies of recombination we found little evidence for an association between pairing failure and X chromosome nondisjunction, but our results suggest that increased recombination near the centromere may play a role in the etiology of the 47,XXX condition.

Adolescent↗
PubMed1988

Klinefelter's syndrome: an analysis of the origin of the additional sex chromosome using molecular probes.

The results of our study of the origin of the additional X chromosome in 39 males with a 47,XXY chromosome constitution are reported. We used a total of 20 X-linked RFLPs and successfully determined the origin of all 32 patients in whom DNA from both parents was available, and a further 3 in whom DNA was available from the patient and mother only. Males whose additional X chromosome was maternal in origin were further investigated using an X-linked centromere specific probe to determine the cell division at which the error occurred. Our results showed 53% of the non-disjunction to be attributable to pat mei I errors, 34% to mat mei I errors, 9% to mat mei II errors and 3% to a post-zygotic mitotic error. In the great majority of patients resulting from an error of maternal meiosis there was clear evidence of recombination involving the non-disjoined chromosomes, suggesting that absence of recombination is not an important aetiological factor in non-disjunction of the X chromosome in female meiosis. There was no alteration of parental age associated with the paternally derived 47,XXY males but a marked increase in maternal age among the maternally derived 47,XXY males, the increase being associated with mat mei I but not mat mei II errors. The proportion of paternally and maternally derived cases was similar among different ascertainment classes, suggesting that there is no dramatic effect of parental origin of the additional X chromosome on the phenotype of 47,XXY males.

Age Factors↗
PubMed1988

Trisomy 21 (Down syndrome): studying nondisjunction and meiotic recombination by using cytogenetic and molecular polymorphisms that span chromosome 21.

By combining molecular and cytogenetic techniques, we demonstrated the feasibility and desirability of a comprehensive approach to analysis of nondisjunction for chromosome 21. We analyzed the parental origin and stage of meiotic errors resulting in trisomy 21 in each of five families by successfully using cytogenetic heteromorphisms and DNA polymorphisms. The 16 DNA fragments used to detect polymorphisms spanned the length of the long arm and detected recombinational events on nondisjoined chromosomes in both maternal meiosis I and maternal meiosis II errors. The meiotic stage at which errors occurred was determined by sandwiching the centromere between cytogenetic heteromorphisms on 21p and an informative haplotype constructed using two polymorphic DNA probes that map to 21q just below the centromere. This study illustrates the necessity of combining cytogenetic polymorphisms on 21p with DNA polymorphisms spanning 21q to determine (1) the source and stage of meiotic errors that lead to trisomy 21 and (2) whether an association exists between nondisjunction and meiotic recombination.

Chromosome Banding↗
PubMed1987

Trisomy 13 ascertained in a survey of spontaneous abortions.

In a series of 2922 karyotyped spontaneous abortions, 62 were found to be trisomic for chromosome 13, 46 having a simple trisomy and 16 a translocation trisomy. The epidemiology of this series of trisomy 13 conceptuses is presented and compared to that of trisomy 13 ascertained from other populations. In most compared parameters the trisomy 13 spontaneous abortions are very similar. However, there is no evidence in our material for the fall in proportion of trisomy 13 conceptuses at very advanced maternal ages that has been reported in three previous studies, one of spontaneous abortions and two of amniocentesis specimens.

Abortion, Spontaneous↗
PubMed1984

Trisomy in man.

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Abnormalities, Drug-Induced↗
PubMed1982

Cytogenetic surveillance of spontaneous abortions.

During the five years of a cytogenetic study on spontaneous abortions in Hawaii there have been significant increases in the frequencies of triploidy of maternal origin and trisomy 16, a significant decrease in sex chromosome monosomy, and variation without trend in the frequency of tetraploidy. Attempts to explain these results in terms of technical factors or changes in maternal and gestational age have been unsuccessful, as have preliminary attempts to identify viral, pharmacological, or other causes. Apparently the etiology of chromosomal abnormality is variable over a few years even in a stable population. Research to identify these causes is continuing on the supposition that variable risks can be reduced.

Abortion, Spontaneous↗
PubMed1980

A cytogenetic study of repeated spontaneous abortions.

During a cytogenetic study of spontaneous abortions, successive abortions from 40 couples were karyotyped. The chromosome constitutions of the first and second abortions were found to be highly correlated. In each of 21 instances in which the first abortion was chromosomally normal, the subsequent abortion(s) was normal as well. In nine cases, the two abortions were chromosomally abnormal, and in four of these, both abortions were trisomic. Combined with findings from other studies of consecutive spontaneous abortions, the present data indicate that certain couples are at an increased risk for either repeated chromosomally normal abortions or for repeated trisomic conceptions. The increased risk of trisomy does not seem to be restricted to a particular chromosome, and the magnitude of the risk increase appears to be independent of maternal age.

Abortion, Habitual↗
PubMed1978

A cytogenetic study of spontaneous abortions in Hawaii.

Cytogenetic results on 234 spontaneous abortions showed 109 (46.6%) to have a chromosome abnormality. The results were analysed separately for the four major ethnic groups of which the population was composed and no differences in the proportion or types of chromosome abnormalities seen. The results of this survey were found to be very similar to other major published surveys and it therefore appears, on present evidence, that neither geographic location nor racial group affects the frequency of chromosome abnormalities seen among human spontaneous abortions. The sex ratio among the chromosomally normal and abnormal abortuses and the effect of parental and gestational age were discussed.

Abortion, Spontaneous↗
PubMed1978

The origin of human triploids.

A series of 26 triploid foetuses was ascertained in a survey of spontaneous abortuses and the origin of the additional haploid complement determined in 21 of them by the study of foetal and parental heteromorphisms. In 17 the additional haploid set was paternal in origin, in 3 it was maternal in origin and in one the parental origin could not be determined. The best fit for the data using a maximum-likelihood method was that 66.4% of the triploids were the result of dispermy, 23.6% the result of fertilization of a haploid ovum by a diploid sperm formed by failure of the first meiotic division in the male and 10% the result of a diploid egg formed by failure of the first maternal meiotic division. The possible sources of error inherent in the technique are reviewed and our results compared with previously published data.

Chromosomes, Human↗
PubMedDate not supplied

Aberrant recombination and the origin of Klinefelter syndrome.

Trisomy is the most commonly identified chromosome abnormality in humans, occurring in at least 4% of all clinically recognized pregnancies; it is the leading known cause of pregnancy loss and of mental retardation. Over the past decade, molecular studies have demonstrated that most human trisomies originate from errors at maternal meiosis I. However, Klinefelter syndrome is a notable exception, as nearly one-half of all cases derive from paternal non-disjunction. In this review, the data on the origin of sex chromosome trisomies are summarized, focusing on the 47,XXY condition. Additionally, the results of recent genetic mapping studies are reviewed that have led to the identification of the first molecular correlate of autosomal and sex chromosome non-disjunction; i.e. altered levels and positioning of meiotic recombinational events.

Chromosome Aberrations↗
PubMedDate not supplied

Risk factors for trisomy 21: maternal cigarette smoking and oral contraceptive use in a population-based case-control study.

PURPOSE: We examined maternal smoking and oral contraceptive use as possible risk factors in the genesis of cases of trisomy 21 of maternal origin. This is the first epidemiological study to categorize cases of trisomy 21 by parent of origin and timing of the meiotic error before assessing possible risk factors. METHODS: We used chromosome 21-specific DNA markers to assign origin to each case. Structured interviews were employed to determine maternal smoking and oral contraceptive use around conception. RESULTS: The odds ratio (OR) for maternal smoking was significantly increased among younger mothers (OR = 2.98; 95% CI = 1.01-8.87), but only in a particular subset of meiotically-derived cases. The combined use of cigarettes and oral contraceptives increased the risk further (OR = 7.62; 95% CI = 1.63-35.6); however, oral contraceptive use alone was not a significant risk factor. CONCLUSION: Our results indicate that categorizing cases of trisomy 21 by parent and timing of the meiotic error allows more precision in identifying risk factors and may shed light on mechanisms of meiotic nondisjunction.

Adult↗