PubMed Health⌕ Search

Biomedical subjects

T Hassold

Publications and source records attributed to T Hassold.

At least 37 records · Page 2Linked to original sources
PubMed1994

The origin of 47,XXY and 47,XXX aneuploidy: heterogeneous mechanisms and role of aberrant recombination.

We investigated the parent and cell division of origin of the additional sex chromosome in 142 males with a 47,XXY constitution and 50 females with a 47,XXX constitution. In 66 of the 47,XXY males the additional chromosome was paternal in origin and in 76 it was maternal in origin, while among the 47,XXX females only 5 had an additional paternal X chromosome, the remaining 45 having an additional maternal chromosome. Among the 107 maternally derived aneuploids for whom it was possible to determine the cell division of origin, 73 were the result of a mat MI error, 24 the result of a mat MII error and 10 the result of a post zygotic mitotic (PZM) error involving the maternal X chromosome. Among those in which the non-disjunction was attributable to an error at the first meiotic division (MI) we observed three different mechanisms of origin. Approximately 30% were associated with complete absence of recombination (nullichiasmate); approximately 24% were associated with a normal number of recombinant events but an abnormal distribution of exchanges (perturbed recombination), while approximately 45% were associated with a normal number and distribution of recombinant events (normochiasmate). Nondisjunction due to an error at the second meiotic division (MII) was associated with a slight reduction in the total number of recombinant events and an abnormal distribution of exchanges. Thus of the four different meiotic mechanisms of origin, three were associated with an abnormal number and/or distribution of exchange events. There was no evidence of an increased paternal age in the aneuploids of paternal origin.(ABSTRACT TRUNCATED AT 250 WORDS)

Aneuploidy↗
PubMed1994

A systematic search for uniparental disomy in carriers of chromosome translocations.

A systematic search was made for uniparental disomy in carriers of apparently balanced chromosome translocations who also had unexplained abnormalities of mental or physical development. Of 65 families studied, biparental origin of both translocated chromosomes was demonstrated in 64, and only 1 case of maternal uniparental disomy of chromosome 14 was detected in the carrier of a Robertsonian t(13q14q). We conclude that uniparental disomy is a rare occurrence in this population.

Chromosome Aberrations↗
PubMed1993

Trisomy in humans: incidence, origin and etiology.

Molecular studies conducted over the past year have demonstrated the importance of aberrant genetic recombination in the etiology of several human trisomies, and have begun to shed light on the basis of the association between advancing maternal age and trisomy. Preliminary studies of gametes using fluorescence in situ hybridization indicate that this will be a useful approach in the analysis of human non-disjunction.

Animals↗
PubMed1992

Molecular and cytogenetic investigation of complex tissue-specific duplication and loss of chromosome 21 in a child with a monosomy 21 phenotype.

Several recent molecular studies have suggested that the clinical phenotype of Down syndrome may be due to triplication of 21q22 [McCormick et al., 1989] as initially suggested by Niebuhr [1974], and perhaps just 21q22.2 [Korenberg et al., 1989, 1990; Rahmani et al., 1989]. Recently, we studied a patient with a phenotype inconsistent with Down syndrome, whose lymphocyte karyotype on several occasions detected only 46,XX,-21, + dic(21)(qter----p11::p11----qter). Combined karyotype and molecular studies on both lymphocytes and fibroblasts allowed correct identification of the abnormality as a complex monosomy/trisomy 21 mosaicism involving a marker derived from idic (21) (p11), and probable assignment of a maternal origin for the error(s). The patient's phenotype was found to be most consistent with monosomy 21. Detailed study of our patient underscores (1) the need for confirmation that there is phenotype/karyotype correlation and (2) the usefulness of molecular analyses to complement the cytogenetic interpretation of marker chromosomes.

Abnormalities, Multiple↗
PubMed1992

Characterization and molecular analysis of nondisjunction in 18 cases of trisomy 21 and leukemia.

We recently began a cytogenetic and molecular study of nondisjunction in leukemic Down syndrome individuals to determine whether the mechanism by which the extra chromosome 21 originates predisposes the individual to leukemia. In the present report, we summarize our observations on 18 patients with trisomy 21 and acute or transient leukemia, including 11 patients with acute lymphocytic leukemia, three with acute myeloid leukemia, one with B-cell lymphoma, one with acute megakaryoblastic leukemia, and two with transient leukemia. Results of DNA marker studies of the parental origin of the extra chromosome 21 indicated that 16 of the 18 cases (89%) were maternally derived, a percentage similar to that seen among nonleukemic Down syndrome patients. We noted that most leukemic Down syndrome patients had one locus or more in which parental heterozygosity was maintained in the trisomic individual, indicating a meiotic rather than a mitotic origin for the trisomy.

Adolescent↗
PubMed1992

Molecular studies of parental origin and mosaicism in 45,X conceptuses.

The present report summarizes molecular studies of parental origin and sex chromosome mosaicism in forty-one 45,X conceptuses, consisting of 29 spontaneous abortions and 12 liveborn individuals with Turner syndrome. Our studies indicate that most 45,X conceptuses have a single, maternally derived X chromosome, regardless of whether the conceptus is liveborn or spontaneously aborted. In studies of mosaicism, our identification of X- and Y-chromosome mosaics among 45,X spontaneous abortions indicates that mosaicism does not ensure survival to term of 45,X fetuses. However, the incidence of sex chromosome mosaicism is substantially higher in liveborn than in aborted 45,X conceptuses, indicating that the presence of a second cell line increases the likelihood of survival to term.

Abortion, Spontaneous↗
PubMed1992

Characterization of three VNTR systems at D21S112.

D21S112 is a highly polymorphic marker on the long arm of chromosome 21. Our analysis of this locus indicated the presence of three VNTR systems. We estimated the heterozygosity of each system and sequenced one of the repetitive regions. Utilizing PCR, we demonstrated that the sequenced VNTR is responsible for the system with the highest level of heterozygosity. Combining data from the three systems makes D21S112 one of the most informative loci on the chromosome.

Base Sequence↗
PubMed1991

Maternal uniparental disomy for chromosome 14.

We report the first case of maternal uniparental disomy of chromosome 14 in humans. The male proband inherited a balanced 13;14 Robertsonian translocation from his mother. Molecular studies showed that neither chromosome 14 was of paternal origin. The proband is of above average intelligence, but he has hydrocephalus, a bifid uvula, premature puberty, short stature, and small testes. It is not known if the clinical findings are related or coincidental to the uniparental disomy.

Blotting, Southern↗
PubMed1990

Nondisjunction of chromosome 21.

Chromosome heteromorphisms and restriction fragment length polymorphisms were used to study the origin of the extra chromosome in 54 trisomy 21 conceptuses. The parental origin was determined in 43 cases, with 39 (91%) being maternally and 4 (9%) parentally derived. Analysis of recombination demonstrated the presence of one or two cross-overs in most cases for which sufficient information was available, suggesting that failure to pair/exchange at meiosis I is relatively unimportant in the genesis of trisomy 21.

Adult↗
PubMed1990

Analysis of non-disjunction in sex chromosome tetrasomy and pentasomy.

X-linked DNA markers were used to determine the parental origin of the additional sex chromosomes in eight individuals with sex chromosome tetrasomy or pentasomy. In all cases studied, one parent contributed a single sex chromosome while the other parent contributed three or four sex chromosomes. Thus, it seems likely that most, if not all, sex chromosome tetrasomy and pentasomy is attributable to successive non-disjunctional events involving the same parent.

Female↗
PubMed1990

A centromere map of the X chromosome from trisomies of maternal origin.

A centromere map is derived from XXX and XXY trisomies of maternal origin. Preliminary data suggest reduced recombination in the tetrads giving rise to mei I nondisjunction, but an excess of recombination in the pericentric region. As in Drosophila, multichiasmate tetrads may be more at risk of nondisjunction than nullochiasmate tetrads.

Animals↗
PubMed1990

The parental origin of the missing or additional chromosome in 45,X and 47,XXX females.

We used X-linked DNA polymorphisms to study the parental origin of the missing or additional X chromosome in conceptuses with 45,X or 47,XXX chromosome constitutions. Fifty-three (80.3%) of 66 cases of sex chromosome monosomy had a maternal X, demonstrating that paternal sex chromosome loss is the most common error leading to this condition. In contrast, 29 (93.5%) of 31 47,XXX cases resulted from maternal nondisjunction. In studies of parental age, we detected no obvious parental age effect for sex chromosome monosomy. For the 47,XXXs, there was an apparent association between increasing maternal age and errors at maternal meiosis I, but not maternal meiosis II. In other analyses, we detected no obvious effect of parental origin on the phenotype of either 45,X or 47,XXX conceptuses, at least as measured by comparing the ratio of paternal:maternal errors among different ascertainment categories.

Aneuploidy↗
PubMed1990

The parental origin of 47,XXY males.

We report the results of our investigation using DNA markers, of the parental origin of 61 XXY males ascertained during cytogenetic studies of consecutive liveborn babies and compare our results with those obtained from a study of 50 XXY males ascertained through clinical referral or amniocentesis. In the former group 44% of newborn XXY males obtained the additional X chromosome from their father and 56% from their mother, while in the latter "referral" group the additional X chromosome was paternally derived in 54% and maternally derived in 46% of the cases. The precise maternal cell division at which nondisjunction occurred was determined in 39 cases of maternal origin. Twenty eight (72%) resulted from an error in the first meiotic division and 11 (28%) from an error in the second meiotic division. There was no evidence of an origin due to a postzygotic mitotic error. There was no significant difference in the parental age at birth between those patients who received the additional X from their father and those who received it from their mother. However, those patients who received the additional X chromosome as a result of a maternal meiotic I error had a higher maternal age than any other category, but the difference reached a level of formal significance only for the clinically referred patients.

Age Factors↗
PubMed1988

Cytogenetic studies of couples with repeated spontaneous abortions of known karyotype.

Several cytogenetic studies have reported an increased frequency of aneuploidy in peripheral blood cultures of couples with multiple spontaneous abortions. However, in none of the studies have the chromosome constitutions of the fetuses been known, making it difficult to interpret these observations. In the present study, we summarize our cytogenetic observations on 23 couples with multiple miscarriages, 12 of whom had repeated chromosomally normal spontaneous abortions, and 11 repeated trisomic spontaneous abortions. We were unable to demonstrate a significant difference in the level of aneuploidy between the two groups. Therefore, it seems unlikely that aneuploidy detectable in peripheral blood preparations is an important indicator of fetal aneuploidy.

Abortion, Habitual↗
PubMed1988

Maternal age in trisomy.

By comparison with a more general theory, data on trisomy in live births, amniocenteses, and spontaneous abortions by year of maternal age are shown to fit a logistic augmented by a proportion independent of maternal age. The frequency of trisomy increases monotonically, with no discrepancy at extremely low or high maternal age. Trisomy 16 is exceptional in that all cases appear to be age-dependent. For groups A, B, and C most trisomies arise by a process independent of maternal age. A small proportion of these trisomies and about half of trisomies for smaller chromosomes (excluding trisomies 16 and perhaps 22) originate by some process dependent on maternal (but not paternal) age and therefore presumably independent of crossingover, which in the female takes place before birth.

Abortion, Spontaneous↗
PubMed1988

A cytogenetic study of 47,XXY males of known origin and their parents.

A number of patients with both sex chromosome aneuploidy and the fragile X syndrome have been reported and this has led to the hypothesis that females heterozygous for the fragile X mutation have an increased rate of meiotic nondisjunction. Furthermore the suggestion has frequently been made that a predisposition to meiotic nondisjunction is associated with an increase in mitotic nondisjunction. We have tested these two hypotheses by examining the chromosomes of a series of 47,XXY males and their parents. In the majority the parental origin of the additional sex chromosome was known. The cells were cultured under conditions suitable for demonstrating the fragile X and 100 cells were scored 'blind' from the patients and both parents. No fragile X individual was seen and there was no difference in the proportion of aneuploid cells between the parents in whom the nondisjunction event occurred and the control parents. Therefore, our results lend no support to the suggestions that the fragile X is associated with an increase in sex chromosome aneuploidy or that individuals in whom meiotic nondisjunction occurs have an increased level of mitotic nondisjunction.

Adolescent↗