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1.
Inherited structural cytogenetic abnormalities detected incidentally in fetuses diagnosed prenatally: frequency, parental-age associations, sex-ratio trends, and comparisons with rates of mutants 总被引:5,自引:2,他引:3
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E B Hook D M Schreinemachers A M Willey P K Cross 《American journal of human genetics》1984,36(2):422-443
Rates of structural chromosome abnormalities were analyzed in 24,951 fetuses studied prenatally in which there were no grounds to suspect an inherited abnormality. In about one in 200 prenatal cytogenetic diagnoses, an unexpected structural abnormality was found. The observed rate was 5.3 per 1,000, of which 1.7 per 1,000 were unbalanced and 3.6 per 1,000 balanced. The rate of inherited abnormalities was 3.1-3.7 per 1,000 (0.4-0.9 per 1,000 for unbalanced abnormalities and 2.6-2.8 per 1,000 for balanced abnormalities). The rate of mutants in this series was, by contrast, 1.6-2.2 per 1,000 (0.8-1.2 per 1,000 for unbalanced abnormalities and 0.8-1.0 per 1,000 for balanced abnormalities). The rate of balanced Robertsonian translocation carriers was 0.6 per 1,000 (about 0.25 per 1,000 for mutants and 0.35 per 1,000 for inherited abnormalities), and for other balanced abnormalities, 3.0 per 1,000 (about 0.6 per 1,000 for mutants and 2.4 per 1,000 for inherited abnormalities). The rates of unbalanced Robertsonian translocations was about 0.1 per 1,000, almost all of which were mutants. For supernumerary rearrangements, the rate was 0.9 per 1,000 (about 0.4 per 1,000 inherited and 0.5 per 1,000 mutant). The rates of all unbalanced (nonmosaic) inherited abnormalities (4.0-5.2 per 10,000) were intermediate between higher rates estimated in all conceptuses (9.1-15.8 per 10,000) and rates observed in newborns (1.5-2.5 per 10,000). This trend is probably attributable to fetal mortality associated with unbalanced rearrangements. The rates of balanced (nonmosaic) inherited abnormalities (26.0-28.0 per 10,000), however, were considerably higher than the rates in all conceptuses (13-16.7 per 10,000) or in all live births (12.2-16.0 per 10,000). The major difference was in the rate of inversions. The use of "banding" methods in the studies of amniocentesis but not in most of the live births or abortus studies probably contributes to at least some of these differences. One trend in parental age among the inherited abnormalities was noteworthy. Paternal age was elevated for inherited balanced reciprocal structural abnormalities of paternal origin but not of maternal origin. With regard to sex ratio, there was a greater proportion of females than males among the unbalanced rearrangements both inherited and mutant. There was no obvious sex difference among the balanced rearrangements. 相似文献
2.
Paternal age and Down's syndrome genotypes diagnosed prenatally: No association in New York State data 总被引:5,自引:0,他引:5
Summary An investigation of a paternal age effect independent of maternal age was undertaken for 98 cases of Down's syndrome genotypes diagnosed prenatally compared to 10,329 fetuses with normal genotype diagnosed prenatally in data reported to the New York State Chromosome Registry. The mean of the difference (delta) in paternal age of cases compared to those with normal genotypes after controlling for maternal age, was slightly negative,-0.27 with a 95% confidence interval of-1.59 to +1.06. A regression analysis was also done in which the data were first fit to an equation of the type lny=(bx+c) and then to the equation ln y=(bx+dz+c) where y = rate of Down's syndrome, x = maternal age, z = paternal age, and b, d, and c are parameters. This also revealed no evidence for a paternal age effect. The value of d (the paternal age coefficient) was in fact slightly negative,-0.0058, with an asymptotic 95% confidence interval of-0.0379 to +0.0263. Lastly, multiple applications of the Mantel-Haenszel test considering various boundaries in paternal age also revealed no statistically significant evidence for a paternal age effect independent of maternal age. These results are at variance with claims of others elsewhere of a very strong paternal age effect detected in studies at prenatal diagnoses. Five different hypotheses are suggested which may account for discrepancies among studies to date in findings on paternal age effects for Down's syndrome: (i) there are temporal, geographic, or ethnic variations in paternal age effects, (ii) there is no paternal age effect and statistical fluctuation accounts for all trends to date; (iii) methologic artifacts have obscured a paternal age effect in some studies which did not find a positive outcome; (iv) methodologic artifacts are responsible for the positive results in some studies to date; (v) there is a rather weak paternal age effect independent of maternal age in most if not all populations, but because of statistical fluctuation the results are significant only in some data sets. The results of all data sets to date which we have been able to analyze by one year intervals are consistent with a mean delta of +0.04 to +0.48 and in the value of d (the paternal age coefficient) of +0.006 to +0.017, and it appears the fifth hypothesis cannot be excluded. Projections based on this assumption are presented. 相似文献
3.
Nikitina NV Bushueva OA Nikolaeva EB Pavlov GV Lurie IW 《Genetic counseling (Geneva, Switzerland)》2003,14(2):181-186
A 5-year-old boy with Silver-Russell-like phenotype and developmental delay was found to have a ring chromosome 15. The same r(15) was found in his slightly mentally retarded mother with mild dysmorphism. Analysis of the literature showed 34 families with direct vertical transmission of a ring autosome. In 30 of these families abnormal chromosomes were inherited from the mothers; both maternal and paternal transmission was shown in different generations of one family; and only in 3 families ring chromosomes were inherited from the fathers. The possible explanations of preponderance of maternal transmission are briefly discussed. 相似文献
4.
Rates of mutant structural chromosome rearrangements in human fetuses: data from prenatal cytogenetic studies and associations with maternal age and parental mutagen exposure. 总被引:5,自引:3,他引:2
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E B Hook D M Schreinemachers A M Willey P K Cross 《American journal of human genetics》1983,35(1):96-109
In 27,225 prenatal cytogenetic studies of amniotic fluid reported to the New York State Chromosome Registry and the United States Interregional Chromosome Register System, there were 61 cases with a structural chromosomal abnormality not known inherited, a rate per 1,000 of 2.24. Of these 33, 1.21 per 1,000 were known de novo and nonmosaic; consequently, the rate of events resulting from germinal mutation is highly likely to be between these two limits. The rates per 1,000 of unbalanced abnormalities were 0.59-1.29; of balanced abnormalities, 0.62-0.96; of balanced Robertsonian translocations, 0.22-0.29; and of unbalanced Robertsonian translocations, 0.07-0.11. The rates of fetuses with supernumerary markers and fragments were unexpectedly high: 0.26-0.70 per 1,000. These abnormalities were associated with increased maternal age (38.0 +/- 5.4 to 38.4 +/- 3.6 compared to 35.6 +/- 4.3 in controls), but even after adjustment for the bias to preferential study of older women, the observed rates of these supernumerary abnormalities were greater than would be expected from live-birth studies or rates estimated in all recognized conceptuses. There were trends to elevated maternal age for the group of all balanced rearrangements, and to diminished maternal age for the nonsupernumerary, non-Robertsonian unbalanced rearrangements. In 136 women studied primarily because of exposure to a putative mutagen, a de novo deletion and an inversion not known inherited were detected. The rate of abnormality in these 136, 1.47%, was significantly greater than the rate of abnormality in the remainder: 0.14%-0.22%. 相似文献
5.
A search for a paternal-age effect upon cases of 47, +21 in which the extra chromosome is of paternal origin 总被引:4,自引:2,他引:2
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If there is a paternal-age effect for 47, +21, it would appear most likely to be present primarily, if not exclusively, in cases in which the extra chromosome is of paternal origin. To search for such an effect, data were reviewed from seven series reporting at least four cases of 47, +21 of paternal origin. The mean of the paternal age-maternal-age difference of such cases (dp) in each series was compared with the mean of the paternal-age differences of cases in the same series that were of maternal origin (dm). If the difference between these (dp - dm or delta) is greater than zero, then this would imply a positive paternal-age effect among cases of paternal origin, at least compared to those of maternal origin. In the seven series, the values of delta ranged from -2.2 years to +3.4 years, and there was no evidence in these comparisons for any consistent trend. A second analysis controlled for any effect of maternal-age variation upon this difference. Each case of paternal origin was matched with a case of maternal origin in the same series that was of the same maternal age. Of 60 cases of paternal origin, exact matches were found for 38. In these 38, the mean value of the difference in parental ages, dp - dm or delta, was negative, about -1.1 (+/- 5.1 years). The difference was highest for the nine cases of paternal origin in which the extra chromosome resulted from presumptive second-division non-disjunction, -1.8 (+/- 3.8 years).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
6.
Uniparental heterodisomy for chromosome 14 in a phenotypically abnormal familial balanced 13/14 Robertsonian translocation carrier. 总被引:16,自引:8,他引:8
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J C Wang M B Passage P H Yen L J Shapiro T K Mohandas 《American journal of human genetics》1991,48(6):1069-1074
A 9-year-old mentally retarded girl with multiple congenital anomalies was found to carry a balanced 13/14 Robertsonian translocation [45,XX,t(13q14q)] which was also present in her father. Her mother carried a balanced reciprocal translocation between chromosomes 1 and 14 [46,XX,t(1;14) (q32;q32)]. Both of her parents were phenotypically normal. Molecular studies were carried out to determine the parental origin of chromosomes 1, 13, and 14 in the patient. Using probes for D14S13 and D14S22, we could show that the patient inherited both chromosomes 14 from her father and none from her mother. Similar studies using probes for chromosomes 1 (D1S76) and 13 (D13S37) loci showed the presence of both maternal and paternal alleles in the patient. Our findings indicate that paternal uniparental heterodisomy for chromosome 14 most likely accounts for the phenotypic abnormalities observed in our patient. It is suggested that uniparental disomy may be the basis for abnormal development in at least some phenotypically abnormal familial balanced-translocation carriers. 相似文献
7.
Five polymorphic index markers were analyzed by polymerase chain reaction (PCR) to ascertain the parental origin of the extra X chromosomes in seven polysomic cases (one 49,XXXXX, three 49,XXXXY, two 48,XXXY, and one 48, XXYY). All four X chromosomes in 49, X polysomies were maternal in origin and the extra X chromosomes in 48 X polysomies were paternal. In each case the multiple X chromosomes were contributed by a single parent. Taken together with previously reported cases, these data support a single mechanism of sequential nondisjunction during either maternal or paternal gametogenesis as the cause of higher order sex chromosome polysomy. 相似文献
8.
Claudia Hepperger Andreas Mayer Julia Merz Dirk K. Vanderwall Steffen Dietzel 《Chromosoma》2009,118(3):335-347
Whether chromosome sets inherited from father and mother occupy separate spaces in the cell nucleus is a question first asked
over 110 years ago. Recently, the nuclear organization of the genome has come increasingly into focus as an important level
of epigenetic regulation. In this context, it is indispensable to know whether or not parental genomes are spatially separated.
Genome separation had been demonstrated for plant hybrids and for the early mammalian embryo. Conclusive studies for somatic
mammalian cell nuclei are lacking because homologous chromosomes from the two parents cannot be distinguished within a species.
We circumvented this problem by investigating the three-dimensional distribution of chromosomes in mule lymphocytes and fibroblasts.
Genomic DNA of horse and donkey was used as probes in fluorescence in situ hybridization under conditions where only tandem
repetitive sequences were detected. We thus could determine the distribution of maternal and paternal chromosome sets in structurally
preserved interphase nuclei for the first time. In addition, we investigated the distribution of several pairs of chromosomes
in human bilobed granulocytes. Qualitative and quantitative image evaluation did not reveal any evidence for the separation
of parental genomes. On the contrary, we observed mixing of maternal and paternal chromosome sets. 相似文献
9.
Norio Niikawa Han-Xiang Deng Kyohko Abe Naoki Harada Toshihisa Okada Hiroyuki Tsuchiya Izumi Akaboshi Ichiro Matsuda Yoshimitsu Fukushima Yasuhiko Kaneko Akira Kuwano Tadashi Kajii 《Human genetics》1991,87(5):561-566
Summary The parental origin of the extra chromosome 21 was studied in 20 patients with trisomy 21-associated transient myeloproliferative syndrome (TMS) using chromosomal heteromorphisms as markers; this was combined with a study of DNA polymorphisms in 5 patients. Of these, 10 were shown to result from duplication of a parental chromosome 21, viz., maternal in 8 and paternal in 2. A patient with Down syndrome-associated TMS had a paracentric inversion in two of his three chromosomes 21 [47,XY,-21, +inv(21)(q11.2q22.13)mat, +inv(21)(q11.2 q22.13)mat). These findings support our hypothesis of disomic homozygosity of a mutant gene on chromosome 21 in 21-trisomic cells as being a mechanism responsible for the occurrence of TMS. The finding also suggests that the putative TMS gene locus is at either 21q11.2 or 21q22.13, assuming that the gene is interrupted at either site because of the inversion. The study of 5 TMS patients using DNA polymorphic markers detected a cross-over site on the duplicated chromosomes 21 between 21q11.2 (or q21.2) and 21q21.3 in one patient, and a site between 21q21.3 and q22.3 in another patient, evidence that confined the gene locus to the 21cen-q21.3 segment. These findings suggest that the putative TMS gene is located at 21q11.2. The extra chromosome 21 in the latter two TMS patients probably resulted from maternal second meiotic non-disjunction, in view of the presence of recombinant heterozygous segments on their duplicated chromosomes 21. 相似文献
10.
A J Staples G R Sutherland E A Haan S Clisby 《American journal of human genetics》1991,49(5):1014-1024
During 1960-89 687 Down syndrome live births and 46 Down syndrome pregnancy terminations were identified in South Australia. Ascertainment was estimated to be virtually complete. The sex distribution of Down syndrome live births was found to be statistically different from the non-Down syndrome live-birth sex distribution (P less than .01). Smoothed maternal age-specific incidence was derived using both maternal age calculated to the nearest month and a discontinuous-slope regression model. The incidence of Down syndrome at birth for the study period was estimated to be 1.186 Down syndrome births/1,000 live births. Annual population incidence was shown to be correlated with trends in the maternal age distribution of confinements. If current trends in the maternal age distribution of confinements continue, the population incidence of Down syndrome in South Australia is predicted to exceed 1.5 Down syndrome births/1,000 live births during the 1990-94 quinquennium. 相似文献
11.
Ernest B. Hook 《Human genetics》1981,59(3):235-239
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. 相似文献
12.
E B Hook 《American journal of human genetics》1983,35(6):1307-1313
Preferential survival in older mothers of fetuses with Down syndrome has been proposed as contributing to the maternal-age effect of this condition. If correct, this provocative hypothesis, which may be termed "relaxed selection," has major implications for approaches to prevention of Down syndrome live births in older women. Several predictions of this hypothesis are examined here by comparisons of parental ages among various populations. These revealed that: (1) mean maternal age of Down syndrome live births is slightly lower than that of Down syndrome spontaneous fetal deaths; (2) mean maternal age of those with mutant D/21 translocation Down syndrome is about the same as that of controls; (3) the ages of Down syndrome mothers who have Down syndrome live births is slightly lower than ages of Down syndrome mothers who have unaffected live births; and (4) in recent data on 47, +21 cases in which the extra chromosome 21 is of paternal origin, the mean maternal ages are 4-5 years lower than the maternal ages of cases of maternal origin (in contrast to earlier reports). All of these observations are contrary to the hypothesis that relaxed selection contributes significantly to the maternal-age association of Down syndrome. If there is any effect of relaxed selection, it is likely to be very weak and/or act primarily upon abortions that occur before recognition of pregnancy. 相似文献
13.
J H Knoll K A Glatt R D Nicholls S Malcolm M Lalande 《American journal of human genetics》1991,48(1):16-21
Genetic imprinting has been implicated in the etiology of two clinically distinct but cytogenetically indistinguishable disorders--Angelman syndrome (AS) and Prader-Willi syndrome (PWS). This hypothesis is derived from two lines of evidence. First, while the molecular extents of de novo cytogenetic deletions of chromosome 15q11q13 in AS and PWS patients are the same, the deletions originate from different parental chromosomes. In AS, the deletion occurs in the maternally inherited chromosome 15, while in PWS the deletion is found in the paternally inherited chromosome 15. The second line of evidence comes from the deletion of an abnormal parental contribution of 15q11q13 in PWS patients without a cytogenetic and molecular deletion. These patients have two maternal copies and no paternal copy of 15q11q13 (maternal uniparental disomy) instead of one copy from each parent. By qualitative hybridization with chromosome 15q11q13 specific DNA markers, we have now examined DNA samples from 10 AS patients (at least seven of which are familial cases) with no cytogenetic or molecular deletion of chromosome 15q11q13. Inheritance of one maternal copy and one paternal copy of 15q11q13 was observed in each family, suggesting that paternal uniparental disomy of 15q11q13 is not responsible for expression of the AS phenotype in these patients. 相似文献
14.
Coveler KJ Yang SP Sutton R Milstein JM Wu YQ Bois KD Beischel LS Johnson JP Shaffer LG 《Human genetics》2002,110(3):251-256
Uniparental disomy of chromosome 14 (UPD 14) results in one of two distinct abnormal phenotypes, depending upon the parent of origin. This discordance may result from the reciprocal over-expression and/or under-expression of one or more imprinted genes. We report a case of segmental paternal isodisomy for chromosome 14 with features similar to those reported in other paternal disomy 14 cases. Microsatellite marker analysis revealed an apparent somatic recombination event in 14q12 leading to proximal biparental inheritance, but segmental paternal uniparental isodisomy distal to this site. Analysis of monochromosomal somatic cell hybrids containing either the paternally inherited or the maternally inherited chromosome 14 revealed no deletion of the maternally inherited chromosome 14 and demonstrated the presence of paternal sequences from D14S121 to the telomere on both chromosomes 14. Thus, the patient has paternal isodisomy for 14q12-14qter. Because the patient shows most of the features associated with paternal disomy 14, this supports the presence of the imprinted domain(s) distal to 14q12 and suggests that the proximal region of chromosome 14 does not contain imprinted genes that contribute significantly to the paternal UPD 14 phenotype. 相似文献
15.
Paola Maraschio Orsetta Zuffardi Franca Bernardi M. Bozzola C. De Paoli Christa Fonatsch Sibylle D. Flatz Loretta Ghersini G. Gimelli M. Loi Renata Lorini Diletta Peretti Lisa Poloni Daniela Tonetti Roberta Vanni G. Zamboni 《Human genetics》1981,57(4):345-350
Summary Eight patients are reported with a de nov extra inverted duplicated chromosome 15. The abnormal chromosome was considered to be the same in all cases, but its precise delineation remained uncertain and was defined as either 15qter15q12::15q1215pter or 15pter15q11::15q1315pter. Analysis with various techniques of the satellite regions of the bisatellited chromosomes demonstrated maternal derivation in six and paternal derivation in one of the seven families. A nonsister chromatid exchange between the two homologous chromosomes 15 is considered a likely origin of the inv dup(15) in the cases with maternal derivation; in the only case of paternal derivation, however, the abnormal chromosome originated from one single chromosome 15. The clinical findings confirm that patients with inv dup(15) have mental and developmental retardation and are frequently affected by seizures, while severe physical malformations are absent. 相似文献
16.
Parent-of-origin effects on seed development in Arabidopsis thaliana require DNA methylation 总被引:3,自引:0,他引:3
Adams S Vinkenoog R Spielman M Dickinson HG Scott RJ 《Development (Cambridge, England)》2000,127(11):2493-2502
Some genes in mammals and flowering plants are subject to parental imprinting, a process by which differential epigenetic marks are imposed on male and female gametes so that one set of alleles is silenced on chromosomes contributed by the mother while another is silenced on paternal chromosomes. Therefore, each genome contributes a different set of active alleles to the offspring, which develop abnormally if the parental genome balance is disturbed. In Arabidopsis, seeds inheriting extra maternal genomes show distinctive phenotypes such as low weight and inhibition of mitosis in the endosperm, while extra paternal genomes result in reciprocal phenotypes such as high weight and endosperm overproliferation. DNA methylation is known to be an essential component of the parental imprinting mechanism in mammals, but there is less evidence for this in plants. For the present study, seed development was examined in crosses using a transgenic Arabidopsis line with reduced DNA methylation. Crosses between hypomethylated and wild-type diploid plants produced similar seed phenotypes to crosses between plants with normal methylation but different ploidies. This is consistent with a model in which hypomethylation of one parental genome prevents silencing of alleles that would normally be active only when inherited from the other parent - thus phenocopying the effects of extra genomes. These results suggest an important role for methylation in parent-of-origin effects, and by inference parental imprinting, in plants. The phenotype of biparentally hypomethylated seeds is less extreme than the reciprocal phenotypes of uniparentally hypomethylated seeds. The observation that development is less severely affected if gametes of both sexes (rather than just one) are 'neutralized' with respect to parent-of-origin effects supports the hypothesis that parental imprinting is not necessary to regulate development. 相似文献
17.
Lebo RV Shapiro LR Fenerci EY Hoover JM Chuang JL Chuang DT Kronn DF 《American journal of human genetics》2000,67(3):750-754
A child with maple syrup urine disease type 2 (MSUD2) was found to be homozygous for a 10-bp MSUD2-gene deletion on chromosome 1. Both purported parents were tested, and neither carries the gene deletion. Polymorphic simple-sequence repeat analyses at 15 loci on chromosome 1 and at 16 loci on other chromosomes confirmed parentage and revealed that a de novo mutation prior to maternal meiosis I, followed by nondisjunction in maternal meiosis II, resulted in an oocyte with two copies of the de novo mutant allele. Fertilization by a sperm that did not carry a paternal chromosome 1 or subsequent mitotic loss of the paternal chromosome 1 resulted in the propositus inheriting two mutant MSUD2 alleles on two maternal number 1 chromosomes. 相似文献
18.
Reexamination of paternal age effect in Down's syndrome 总被引:2,自引:0,他引:2
Summary The recent discovery that the extra chromosome in about 30% of cases of 47, trisomy 21 is of paternal origin has revived interest in the possibility of paternal age as a risk factor for a Down syndrome birth, independent of maternal age. Parental age distribution for 611 Down's syndrome 47,+21 cases was studied. The mean paternal age was 0.16 year greater than in the entire population of live births after controlling for maternal age. There was no evidence for a significant paternal age effect at the 0.05 level. For 242 of these Down's syndrome cases, control subjects were selected by rigidly matching in a systematic manner. Paternal age was the variable studied, with maternal age and time and place of birth controlled. There was no statistically significant association between paternal age and Down's syndrome. After adjustment for maternal age, these two studies were not consistent with an increase of paternal age in Down's syndrome. 相似文献
19.
Paternal age and trisomy among spontaneous abortions 总被引:4,自引:0,他引:4
Maureen Hatch Jennie Kline Bruce Levin Michelle Hutzler Dorothy Warburton 《Human genetics》1990,85(3):355-361
Summary The relationship of paternal age to specific types of trisomy and to chromosomally normal loss was investigated in data drawn from a case-control study of spontaneous abortions. Differences in paternal age between karyotype groups and controls delivering after 28 weeks gestation were tested using an urn model analysis which adjusted, by regression, for maternal age and, by stratification, for the effects of design variables (payment status, phase of study) and demographic factors (language, ethnicity). The magnitude of paternal age differences was estimated using least squares regression analysis. For chromosomally normal cases there was no association with paternal age. Among the fourteen trisomy categories examined, four (7, 9, 18, 21) showed increased paternal age ( 1 year above expectation), three (13, 20, 22) showed decreased paternal age and the rest, including the most common, trisomy 16, showed negligible differences. Only the association with trisomy 22 was statistically significant (P = 0.012), with a predicted reduction in paternal age of 2.1 years (95% CI -4.9, -0.5 years). This association did not vary with maternal age, payment status, phase of study, language or ethnicity. Because previous observations are extensive, the relation of paternal age to trisomy 21 was examined further. The overall association was not significant ( = 0.8 years; 95% CI -0.8, 2.4 years). Moreover, there was evidence that the magnitude and direction of paternal age associations vary significantly within the sample, although not between subgroups defined on the basis of payment, phase of study, language or ethnicity. With respect to maternal age, the trend is towards a greater paternal age difference for trisomy 21 losses in younger women (P = 0.058). Given the number of tests performed, the finding for trisomy 22 and reduced paternal age could be due to chance. Among trisomy types, the direction of paternal age associations was not consistent for chromosomes grouped according to characteristics that might relate to the probability of nondisjunction, such as size, arm ratio, or nucleolar organizer region content, or to the potential viability of the trisomy. Thus, neither on statistical nor biological grounds do the data provide compelling evidence of paternal age effects on the trisomies found among spontaneous abortions, or on chromosomally normal losses. 相似文献
20.
Gómez D Solsona E Guitart M Baena N Gabau E Egozcue J Caballín MR 《Annales de génétique》2000,43(1):23-28
We have carried out a population-based study on the origin of the extra chromosome 21 in 38 families with Down syndrome (DS) offspring in El Vallès (Spain). From 1991 to 1994, a higher prevalence of DS (22.7/10000 live births, stillbirths and induced abortions) was found compared to the majority of EUROCAT registries. The distribution of trisomy 21 by origin was 88% maternal (90.6% meiosis I, 6.2% meiosis II, 3.1% maternal mosaicism), 5.6% paternal (50% meiosis I, 50% meiosis II) and 5.6% mitotic. The percentage of parental mosaicism was 2.7%. These percentages are similar to those previously reported. Recombination study revealed a maternal meiosis I genetic map of 32.68 cM (approximately one-half the length of the normal female map). Mean maternal age among non-recombinant cases involving MI errors was significantly lower (31.1 years) than among those cases showing one observable crossover (36.1 years) (P<0.05); this could support the hypothesis that 'achiasmate' chromosomes may be subject to aberrant segregation regardless of maternal age. 相似文献