Human trisomy is attributable to many different mechanisms and the relative importance of each mechanism is highly chromosome specific. The association between altered recombination and maternal non-disjunction is well documented: reductions in recombination have been reported for maternal meiosis I (MI) errors involving chromosomes 15, 16, 18 and 21 and increased recombination has been reported for meiosis II (MII) errors involving chromosome 21. We therefore investigated maternal X chromosome non-disjunction, to determine whether the effects of recombination are unique to the X chromosome or similar to any of the autosomes thus far studied. We genotyped 45 47,XXX females and 95 47,XXY males of maternal origin. Our results demonstrate that 49% arose during MI, 29% during MII and 16% were postzygotic events; a further 7% were meiotic but could not be assigned as either MI or MII because of recombination at the centromere. Among the MI cases, a majority (56%) had no detectable transitions and so absent recombination is an important factor for X chromosome non-disjunction. However, similar to trisomy 15 and unlike trisomy 21, we observed a significant increase in the mean maternal age of transitional MI errors compared with nullitransitional cases. In our studies of MII errors, recombination appeared normal and there was no obvious effect of maternal age, distinguishing our results from MII non-disjunction of chromosomes 18 or 21. Thus, surprisingly, the risk factors associated with both MI and MII non-disjunction appear to be different for virtually every chromosome that has been adequately studied.

INTRODUCTION

Trisomy is the most common chromosomal abnormality in humans and affects 4% of all clinically recognized human pregnancies (1). The rate of non-disjunction varies between different chromosomes and the factors underlying non-disjunction appear to be highly chromosome specific. Most trisomies arise from an error during maternal meiosis (MI). However, there are exceptions and among 47,XXY males the origin is divided almost equally between maternal and paternal non-disjunction (2,3). Among autosomes, paternal non-disjunction accounts for a significant number of cases of trisomies 2 and 8 (4) and, for trisomy 18, maternal meiosis II (MII) errors predominate (5).

The mechanisms underlying non-disjunction are poorly understood, although both increased maternal age and altered recombination are strong aetiological factors. Reduction in recombination has been reported for all autosomal maternal trisomies. For MI errors involving chromosomes 18 (5) and 21 (6,7) this is caused both by absent recombination (achiasmate tetrads) and diminished recombination (a reduced number of exchanges per tetrad). However, for chromosome 16 only diminished recombination is important (8). The effects of maternal age on recombination in MI and MII errors are less clear and may be chromosome specific. For example, in maternal MI errors, there is a direct correlation between exchange frequency and maternal age for trisomy 15 (9), but no such effect has been reported for other autosomal trisomies; in maternal MII errors, increases in maternal age are associated with both trisomies 18 and 21, but recombination is normal for trisomy 18 and increased for trisomy 21.

For maternal sex chromosome trisomies, Macdonald et al. (10) reported that both absent and altered recombination were important in non-disjunction. However, the X centromere marker used in this study, DXZ1, is extremely difficult to interpret reliably (3) and retyping of 94 cases revealed that many actual MII and postzygotic mitotic event (PZM) errors had mistakenly been interpreted as MI. In total, the centromere status had been misassigned in >30% of cases and thus some of the conclusions of McDonald et al. (10) are wrong. We have now determined the stage of origin and the extent and location of recombination in these 94 cases and an additional 46 trisomies. From these data we have determined that the effects of recombination and maternal age on the X chromosome show both similarities and differences to the autosomes thus far studied.

RESULTS

Nomenclature

The terminology used in this paper is similar to that of Robinson et al. (9). Briefly, a chiasma, also called an exchange, occurs between pairs of chromatids during the 4 strand stage. A transition refers to an observed change in marker state from non-reduced (N) to reduced (R), or vice versa, in two non-disjoined strands. Therefore, non-disjoined strands in which no transitions are observed are referred to as nullitransitional, instead of achiasmate, because this term should be applied only to the absence of chiasma in a tetrad. A crossover refers to an observable change in the marker state in a single chromosome.

It should be noted that not all of the exchanges which have occurred in a meiotic tetrad will subsequently be observed as crossovers or transitions. Similarly not all nullitransitional cases observed will have derived from an achiasmate tetrad, rather a proportion will have derived from a tetrad in which an exchange took place but which is not represented in the two non-disjoined strands recovered.

Origin of additional X chromosome

Utilizing 54 loci, which were grouped into 40 megaloci (Table 1) covering the entire X chromosome, we were able to subdivide all 140 cases into groups according to the origin of trisomy. A total of 68 cases (49%) were consistent with an error at MI, of which 38 showed no transitions and 30 showed at least one transition. There were 40 cases (29%) with MII errors, by definition having at least one transition. A total of 22 cases did not exhibit any transitions and were reduced at all informative loci: these were either the result of a PZM or an MII error following a nullitransitional but disjoined MI. In the remaining 10 cases we observed a change in marker state (see Materials and Methods), from N to R or vice versa, between the proximal loci on one chromosome arm and the proximal loci on the other chromosome arm. Thus these cases were clearly meiotic but, with recombination apparently occurring at, or near, the centromere, it was not possible to classify the cases as MI- or MII-derived. A summary of the distribution of the origins of aneuploidy throughout the sample is shown in Table 2

Non-disjunction mapping

Using the map+ program (11) the standard map length of the X chromosome was calculated to be 190.13 cM. Non-disjunction analysis was also performed using the map+program (Table 3). When all MI cases were considered together, the calculated map was considerably shorter than the standard map, suggesting that reduced recombination is an important factor in MI non-disjunction. However, when the MI transitional cases were considered separately, the map length was not significantly different from the standard map length. We also compared the non-disjunction linkage maps with the standard map to assess the possible role of aberrant recombination (Fig. 1). Although there is a small increase in recombination in the p arm, the MI transitional class non-disjunction map did not deviate significantly from the standard curve. This suggests that aberrant recombination is not involved in transitional MI non-disjunction. For the MII class there was also a small increase in p arm recombination, but overall no significant deviation in recombination pattern and no significant change in total map length.

Non-disjunction maps were also prepared by incorporating the unassigned meiotic group into each of the three groups: MI-all, MI transitional and MII. The effect of the 10 unassigned cases was to increase the level of recombination around the centromere but with little effect on recombination in the chromosome arms (data not shown).

Transition and chiasma frequency estimates

The distribution of transitions observed for each non-disjunction class is shown in Table 4. We applied the EXCHANGE program (5) to these data to estimate the chiasma frequency in tetrads and the corresponding map length. There are small differences in the map lengths generated by the EXCHANGE and map+ programs because the EXCHANGE program does not incorporate error filtration or chiasma interference. The length of the standard map, constructed using the map+ program, was 190 cM, corresponding to a mean of 3.8 chiasmata per tetrad. For the MI group, the EXCHANGE program estimated that 47% of tetrads have no chiasmata, χ21 = 25.95, when tested against the null hypothesis that the frequency of achiasmate tetrads (q0) is zero (Table 5). Therefore, of the 38 observed nullitransitionals, ∼32 are derived from achiasmate tetrads. The chiasma distribution estimated for all the MI cases gives a mean of 1.5 chiasmata per tetrad (∼75 cM map length). The same analysis carried out on the MI transitional and MII classes gave mean chiasma frequencies of 3.2 per tetrad (∼160 cM map length) and 3.4 per tetrad (∼170 cM map length), respectively.

Parental age

Parental ages were available for the majority of the 140 cases and we have calculated a mean maternal age for each class of non-disjunction (Table 6). The families in this study were recruited via multiple centres worldwide, over a 12 year period and with a variety of prenatal and postnatal referral reasons. The dates of birth and prenatal sampling ranged from 1948 to 1999. During this time there has been a marked increase in the overall mean maternal age. Therefore, it is not possible to use an appropriate normal control for maternal age. Instead we have calculated a control mean maternal age (28.47 years) from a cohort of mothers of paternally derived sex chromosome trisomies, which are unlikely to be associated with an age effect (12,13).

The t-test statistic was used to ascertain whether any of the groups had a significantly different mean maternal age compared with the control maternal age. The mean maternal age for the group containing all MIs was found to differ significantly from that of the control group (two-tailed P = 0.0003). When the MI group was split into transitionals and nullitransitionals, the nullitransitionals’ mean maternal age was non-significant compared with controls. However, the difference between MI transitionals and normals was extremely significant (two-tailed P = 0.0001). A direct comparison between the two MI classes showed the MI nullitransitionals to have a significantly younger mean maternal age (P = 0.0163).

Correlation analysis was then performed to investigate whether this advanced maternal age effect was related to the observed number of transitions (Table 4). This was not significant for the MI transitional class (P = 0.7525) and therefore the number of transitions is independent of any maternal age effect. In a study on the origin of trisomy 15, Robinson et al. (9) found the mean maternal age of the three or four transition class was significantly higher compared with the one and two transition class considered together. When tested in our cohort of X chromosome aneuploidies, this result was also non-significant.

To test whether significant differences in mean maternal age between MI transitionals and MI nullitransitionals is a feature of other non-disjoined chromosomes, we re-analysed our sample of trisomy 18 data (5). Much of this sample was ascertained through advanced maternal age and so could not be compared with a normal mean maternal age. However, within-sample comparisons are valid. The mean maternal age for the MI nullitransitionals is 32.94 (n = 16, SE = 1.73) and for the MI transitionals is 36.48 (n = 25, SE = 1.31). Although the difference between these groups was not statistically significant (two-tailed P = 0.1059), a larger sample of these data may corroborate the results found in this study.

Neither the MII nor the unassigned classes had significantly different mean maternal ages compared with the controls. However, a statistically significant difference was found between the PZM mean maternal age of 31.65 years and the control mean maternal age (two-tailed P = 0.04). A maternal age effect would not be expected for a postzygotic event and so we tested the ascertainment of the PZM class compared with the others. All data were divided on the basis of ascertainment into postnatal and prenatal groups. Comparison of the PZMs with the remainder of the cohort showed that the PZMs were not enriched for either group (χ21 = 0.09).

Assessment of PZM cases

For genuine PZM cases there should be an equal probability of the duplicated chromosome being maternal or paternal. Therefore, we compared the incidence of maternal and paternal PZM cases among our cohort of 47,XXX females. Seven of the 45 maternal 47,XXX cases were apparently mitotic. From the same project we had ascertained seven 47,XXX cases of paternal origin (10) (N.S. Thomas, unpublished data). Five were informative for the most distal PAR1 or PAR2 markers with three cases resulting from MII errors and only two from a PZM error. Thus there is a slight excess of maternal cases. Although this is not statistically significant, it suggests that a proportion of maternal PZM errors may arise from a nullitransitional MI that does not disjoin at MII. However, as the nullitransitional MI class is not associated with an increased maternal age, contamination with a proportion of nullitransitional cases would not explain the increased maternal age of the PZM class.

From the observed transmission data for the MII class, the EXCHANGE program estimated that the frequency of achiasmate tetrads among MII errors was zero (Table 5). However, by definition all MII errors had at least one observed transition. Therefore, we used the SEGRAN program (14) to determine whether any of the apparent PZM cases were due to an MII error following a nullitransitional MI. We used a hypergeometric distribution (14) to calculate the probable number of zero transitions that occur given the actual distribution of the number of transitions within the MII class. These raw data are 3, 15, 17, 3 and 2, respectively, for the number of transitions 1–5. The hypergeometric distribution was used because it had two advantages over the Poisson distribution, producing a better fit for these data and incorporating interference modelling. The program estimates a value for Π which is the probability of there being >0 transitions given the complete distribution. Given an estimate of Π = 0.9921, the number of cases with zero transitions (x) was calculated, by the formula x = [(1 – Π)N]/Π, to be 0.3185 of the 22 apparent PZM cases. As this value was close to zero and, in agreement with the estimate of the EXCHANGE program, we were content that these cases had been accurately assigned and that the actual PZM distribution did not need correcting with this estimate.

DISCUSSION

Analysis of 140 families has shown that maternal sex chromosome trisomy can arise by several different mechanisms. Some of these mechanisms have parallels with autosomal trisomies whereas others are unique to the X chromosome.

MI nullitransitional

Consistent with most maternal trisomies, MI errors were the single biggest class for the X chromosome, accounting for nearly half of all cases. A majority, 56%, had no observable transitions and 47% were estimated to have derived from achiasmate tetrads. Therefore, complete absence of recombination accounts for a significant proportion of maternal sex chromosome trisomy. This effect appears to be independent of maternal age, in which case the absence of chiasmata may be incompatible with normal chromosome segregation, resulting in non-disjunction irrespective of maternal age. Absent recombination is also important for maternal trisomy of chromosomes 15 (9), 18 (5) and 21 (6,15) and for paternal sex chromosome non-disjunction (12). However, for the maternal trisomies 18 and 21 achiasmate tetrads are associated with advanced maternal age.

MI transitional

The remaining MI cases have apparently normal recombination with no change in map length and no significant deviation from the normal pattern of recombination. Therefore, the overall decrease in recombination associated with all maternal MI trisomies can now be explained in three different ways: (i) a significant proportion of achiasmate tetrads (X chromosome); (ii) a decrease in the mean number of exchanges per tetrad among the MI transitional class (chromosome 16); and (iii) both absent and altered recombination (chromosomes 15, 18 and 21).

However, this class was associated with a significant increase in maternal age compared with both the controls (P = 0.0001) and the MI nullitransitional class (P = 0.016). This is unlike maternal trisomies for chromosomes 16 (8), 18 (5) and 21 (6), which display age-related alterations in recombination. Maternal MI transitional errors of chromosome 15 are associated with a 50% decrease in pericentromeric recombination (9), otherwise the significant difference in mean maternal age between the transitional and nullitransitional classes closely parallels the X chromosome. However, although maternal age was independent of the number of transitions for the X chromosome, for chromosome 15 the maternal age was associated with the level of recombination.

Although non-significant, our re-analysis of trisomy 18 data (5) suggested that for MI errors the mean maternal age of the transition class was also greater than the mean maternal age of the nullitransitional class. For trisomy 21, Lamb et al. (16) found no significant difference in the map lengths of young and old mothers and no difference in the distribution of exchanges. Data from chromosome 16 suggest that the maternal age effect on MI errors is linked to the frequency and location of recombination events (8). Thus, there is no simple relationship between maternal age and recombination. However, the diverse effects of maternal age could all be encompassed by the ‘two-hit’ model proposed by Lamb et al. (16). It is possible that with increasing maternal age the ability to process tetrads with certain ‘at risk’ exchange configurations will decrease and these configurations will be more likely to non-disjoin in older mothers. What constitutes an ‘at risk’ configuration, i.e. the number and/or position of chiasmata on which the maternal age-dependent second hit will act, is chromosome specific. Thus the effect of maternal age will be related to the normal distribution of chiasmata for a particular chromosome or to the presence of chromosome‐specific factors which ensure normal segregation (9).

MII

The third mechanism of X chromosome non-disjunction occurs during MII. Amongst this class, recombination was normal and thus appeared independent of events at MI. There was also no association with increased maternal age, distinguishing maternal MII non-disjunction of the X chromosome from autosomal trisomies. Increases in maternal age are associated with both trisomies 18 (5) and 21 (6), but recombination is normal for trisomy 18 and increased for trisomy 21. Therefore, the effects of maternal age and recombination on MII errors appear to be highly chromosome specific.

Unassigned meiotic errors

The fourth mechanism of X chromosome non-disjunction occurs meiotically but, because of recombination at or very close to the centromere, cannot be classified as MI or MII. This class of error was rare but, given the exceptionally low rate of recombination around the human X centromere (17), the identification of 10 of 140 cases is highly significant. Like MII errors, they do not appear to be associated with advanced maternal age, although they have a greater number of mean transitions than either the MII class (P = 0.0699) or the MI transition class (P = 0.0016). The distribution of transitions in the unassigned cases was also unusual, with increased proximal recombination in addition to recombination at the centromere and the presence of double recombinations within relatively short distances. Thus, this seems to be a novel type of non-disjunction.

A similar mechanism for autosomal trisomies has not been reported, but would be difficult to detect in short or acrocentric chromosomes. Nevertheless, altered recombination around the centromere is an important factor in non-disjunction. The unassigned class closely parallels MII errors of trisomy 21 which are associated with increased proximal recombination and also show an overall excess of recombination (6,16). Proximal chiasmata may predispose to ‘chromosome entanglement’, preventing the bivalent from separating (16), or the resolution of proximal chiasmata may result in premature chromosome separation (18). Alternatively, the effect of recombination on the X chromosome may be unique because the X centromere is different from nearly all autosomal centromeres, being composed of both α and γ satellite DNA (19).

PZM

The fifth mechanism of X chromosome non-disjunction results from a mitotic duplication early in the zygote. This class of maternal error appears more common for the X chromosome than for autosomal trisomies. Since the zygote is presumably formed from two normal monosomic gametes and the error occurs after conception there should be no bias regarding the parental origin of the additional chromosome and no effect of advanced maternal age. Surprisingly, however, this class was associated with a significantly elevated maternal age and there was a slight excess of maternal cases. It is possible that some of these cases are actually MII errors following a nullitransitional MI, as by molecular analysis such cases would also appear to be reduced along the whole length of the chromosome. This cannot explain the effect of maternal age because, for the X chromosome, both maternal MII errors and nullitransitional MI errors are independent of maternal age. However, for chromosome 21, Lamb et al. (7,16) have demonstrated that certain chiasmata distributions laid down during MI predispose to age-dependent non-disjunction at MII, i.e. events at MI and MII are not always independent. We can speculate that for the X chromosome, nullitransitional cases that survive MI may be peculiarly susceptible to some form of maternal age-dependent non-disjunction at MII. If the observed PZM cases can arise by two different mechanisms, one maternal age-dependent and the other maternal age-independent, in a larger sample we would expect the maternal ages of the PZM case to be distributed bimodally.

For MII/nullitransitional MI errors to occur, achiasmate tetrads must be able to segregate at MI. Although this may be able to happen at random, two pieces of evidence from our X chromosome data suggest that there is no ‘back up’ system in humans to allow proper segregation of non-recombined homologous pairs. Firstly, achiasmate MI non-disjunction occurs frequently and, secondly, the SEGRAN program calculated that nearly all MII errors were chiasmate. Similarly, for the autosomes there is no evidence for normal disjunction of achiasmate tetrads (5). The frequency of achiasmate tetrads in normal meiosis is estimated to be zero or near zero for chromosomes 18 (5) and 21 (16), although there may be a low background rate of achiasmate tetrads for chromosome 15 (9). For most autosomal trisomies the numbers of maternal and paternal PZM cases are reported to be roughly equal (7,2022). Therefore, there is no compelling evidence to re-classify any of the apparent PZM cases.

Conclusions

At least five different mechanisms are associated with maternal sex chromosome non-disjunction. Absent recombination is an important factor but, except for the 10 ‘unassigned’ cases, there was no other association with aberrant recombination. Only two of the five mechanisms are associated with increased maternal age, including, surprisingly, the PZM cases. The unassigned class appears to be a novel type of non-disjunction and both the MI and MII mechanisms are distinct from autosomal trisomies. The relationship between maternal age, recombination and non-disjunction appears to be highly chromosome specific. Thus the risk factors associated with non-disjunction appear to be different for virtually every chromosome that has been adequately studied.

MATERIALS AND METHODS

Study population

We have studied 140 cases of maternal sex chromosome trisomy, 95 with a 47,XXY constitution and 45 with a 47,XXX constitution. All karyotypes were apparently non-mosaic. A total of 51 of the 47,XXY cases and 43 of the 47,XXX cases have been described previously by McDonald et al. (10). Of the 44 new 47,XXY cases, 29 were recruited as part of a study into the effect of the parental origin of an additional sex chromosome on behavioural and cognitive phenotypes, 10 were diagnostic referrals and the remaining five were identified during a school survey screening for carriers of the fragile X. Both new cases of 47,XXX were diagnostic referrals. Overall the 47,XXY population comprised 80 postnatal referrals and 15 prenatal referrals (11 for advanced maternal age, 2 because of an elevated serum screen risk, 1 because of maternal anxiety and 1 intrauterine death). The 47,XXX population comprised 35 postnatal referrals and 10 prenatal referrals (8 for advanced maternal age, 1 because of maternal anxiety and 1 because of in vitro fertilization). DNA was extracted from all probands and their parents from either peripheral blood or cheek cells.

Molecular studies

Each case was tested using a panel of markers spanning the X chromosome and, where informative, their results were recorded as either R (where heterozygosity in the mother is reduced to homozygosity in the proband) or N (where heteozygosity in the mother is retained in the proband). The X chromosome contains two pseudoautosomal regions, PAR1 and PAR2, and these are located at the distal tips of the p and q arms, respectively. Diallelic intercrosses with the Y chromosome in these regions were scored as D (if aaa or bbb) or X (if aab or abb) (23).

The panel contains 54 microsatellites. Ten markers within PAR1 and PAR2 have been described previously (12), otherwise all primer sequences and conditions are available from the Genome Data Base (http://www.gdb.org ). There are 21 markers on the p arm and 23 on the q arm. Adjacent markers were grouped into megaloci when recombination was absent between a set of markers. There were 40 megaloci in the standard map (Table 1). The average spacing was 4.75 cM with a maximum gap between loci of 12 cM, with the exception of one interval of 14 cM and one of 15 cM. The meiotic stage of non-disjunction was assigned using a number of pericentromeric markers on the p arm (megalocus e) and on the q arm (megalocus f). The genetic distance between these markers is <1 cM (17) and the intervals between the centromere and megaloci 5 and 6 are 5–6 Mb and <2 Mb, respectively (24) (Location Database: http://cedar.genetics.soton.ac.uk/public_html/ ).

Non-disjunctional mapping

The standard map for the X chromosome was created using the map+ program (http://cedar.genetics.soton.ac.uk/public_html/programs.html ) (11) (for pairwise lods generated from CEPH version 8.2) which constructs maps with an estimable typing error frequency (ε) and a mapping parameter (p). The location of SKK-1 (25) is not known in relation to DXS1073 and so the distance between these loci was arbitrarily assumed to be 1 cM. Non-disjunction analysis was also performed using the map+program to generate linkage maps for the disjoined chromosomes according to the origin of aneuploidy.

ACKNOWLEDGEMENTS

The authors are grateful to all the families and the referral centres who took part in this study and to the staff at the Wessex Regional Genetics Laboratory. This work was supported by the Wellcome Trust.

+

To whom correspondence should be addressed. Tel: +44 1722 429080; Fax: +44 1722 338095; Email: wessex.genetics@dial.pipex.com

Figure 1. Comparison of the standard and non-disjunction genetic maps. The non-disjunction maps are plotted against the standard map on the x-axis with the p telomere at the origin. All genetic distances are given in centiMorgans. The standard map itself appears as a straight line through the origin.

Figure 1. Comparison of the standard and non-disjunction genetic maps. The non-disjunction maps are plotted against the standard map on the x-axis with the p telomere at the origin. All genetic distances are given in centiMorgans. The standard map itself appears as a straight line through the origin.

Table 1.

Loci/megaloci used and their position on the standard map

Locus Standard map location Locus Standard map location 
SHOXa DXS8380 88.69 
DXYS232Xb 2.45 DXS8092 93.83 
DXS2497 3.52 DXS6793 94.07 
DXS1060 8.54 DXS6803 94.87 
DXS996 9.24 DXS990 102.12 
DXS8378 12.85 DXS6809 103.41 
DXS207 23.55 DXS6789 104.91 
DXS999 25.83 DXS8063 111.79 
DXS1226 33.08 DXS6797 114.68 
DXS451 35.7 DXS6804 118.39 
DXS989 38.74 DXS1220 123.5 
DMD 41.48 DXS1001 132.95 
DXS538 51.93 DXS8057 137.21 
DXS1068 53.21 DXS1047 141.77 
DXS993 62.7 DXS984 154.02 
DXS8379c 63.37 DXS8043 167.75 
DXS8083 72.4 DXS6806 169.92 
DXS1199d 84.82 DXS998 174.41 
DXS8032e 84.82 DXS1073g 189.13 
DXS7132f 85.25 SKKh 190.13 
Locus Standard map location Locus Standard map location 
SHOXa DXS8380 88.69 
DXYS232Xb 2.45 DXS8092 93.83 
DXS2497 3.52 DXS6793 94.07 
DXS1060 8.54 DXS6803 94.87 
DXS996 9.24 DXS990 102.12 
DXS8378 12.85 DXS6809 103.41 
DXS207 23.55 DXS6789 104.91 
DXS999 25.83 DXS8063 111.79 
DXS1226 33.08 DXS6797 114.68 
DXS451 35.7 DXS6804 118.39 
DXS989 38.74 DXS1220 123.5 
DMD 41.48 DXS1001 132.95 
DXS538 51.93 DXS8057 137.21 
DXS1068 53.21 DXS1047 141.77 
DXS993 62.7 DXS984 154.02 
DXS8379c 63.37 DXS8043 167.75 
DXS8083 72.4 DXS6806 169.92 
DXS1199d 84.82 DXS998 174.41 
DXS8032e 84.82 DXS1073g 189.13 
DXS7132f 85.25 SKKh 190.13 

aSHOX = DXYS233, SHOX, DXS201, DXS6814, DXS234.

bDXYS232X = DXYS228, DXYS232X.

cDXS8379 = DXS8379, MAOB.

dDXS1199 = DXS1199, DXS1204.

eDXS8032 = DXS8032, AI7, DXS991.

fDXS7132 = DXS7132, HUMAR, DXS1213.

gDXS1073 = DXS1073, DXS1108, DXS1107.

hSKK = SKK–1, DXYS225.

Table 2.

Distribution of all aneuploidies

Origin n Percentage of total 
MI, nullitransitional 38 27.1 
MI, transitional 30 21.4 
MII 40 28.6 
PZM 22 15.7 
Unassigned meiotic errors 10 7.1 
Total 140 100 
Origin n Percentage of total 
MI, nullitransitional 38 27.1 
MI, transitional 30 21.4 
MII 40 28.6 
PZM 22 15.7 
Unassigned meiotic errors 10 7.1 
Total 140 100 
Table 3.

Map length estimates from map+ program

Map Length (cM) SE 
Standard 190.13 6.09 
MI, all 85.57 11.43 
MI, transitionals 186.25 24.06 
MII 204.07 16.80 
Unassigned meiotic errors 213.94 50.16 
Map Length (cM) SE 
Standard 190.13 6.09 
MI, all 85.57 11.43 
MI, transitionals 186.25 24.06 
MII 204.07 16.80 
Unassigned meiotic errors 213.94 50.16 
Table 4.

Observed distribution of transitions within groups

Group No. of transitions         
 Total Mean SE 
MI, all  0.5588 0.0882 0.2353 0.0882 0.0294 0.0000 64 0.94 0.1955 
MI, transitional 0.0000 0.2000 0.5333 0.2000 0.0666 0.0000 64 2.13 0.1496 
MII 0.0000 0.0750 0.3750 0.4250 0.0750 0.0500 106 2.65 0.1457 
Unassigned meiotic errors 0.0000 0.1000 0.1000 0.4000 0.2000 0.2000 33 3.30 0.3958 
Group No. of transitions         
 Total Mean SE 
MI, all  0.5588 0.0882 0.2353 0.0882 0.0294 0.0000 64 0.94 0.1955 
MI, transitional 0.0000 0.2000 0.5333 0.2000 0.0666 0.0000 64 2.13 0.1496 
MII 0.0000 0.0750 0.3750 0.4250 0.0750 0.0500 106 2.65 0.1457 
Unassigned meiotic errors 0.0000 0.1000 0.1000 0.4000 0.2000 0.2000 33 3.30 0.3958 
Table 5.

Estimated chiasma distribution from EXCHANGE program

Group Frequency of chiasmata       
 q0 q1 q2 q3 q4 q5 Mean 
MI, all 0.4698 0.0278 0.1577 0.2239 0.1208 0.0000 1.4981 
MI, transitional 0.0000 0.0000 0.0959 0.6312 0.2729 0.0000 3.1770 
MII 0.0000 0.0000 0.1085 0.5796 0.1183 0.1937 3.3975 
Group Frequency of chiasmata       
 q0 q1 q2 q3 q4 q5 Mean 
MI, all 0.4698 0.0278 0.1577 0.2239 0.1208 0.0000 1.4981 
MI, transitional 0.0000 0.0000 0.0959 0.6312 0.2729 0.0000 3.1770 
MII 0.0000 0.0000 0.1085 0.5796 0.1183 0.1937 3.3975 
Table 6.

Effect of maternal age

 Maternal age   Versus mean control age  
 n Mean SE Difference P value 
Control 70 28.47 0.73 – – 
MI, all 63 32.71 0.88 +4.24 0.0003 
MI, nullitransitional 33 30.73 1.04 +2.26 Not significant 
MI, transitional 30 34.90 1.36 +6.43 0.0001 
MII 38 28.29 1.18 –0.18 Not significant 
PZM 20 31.65 1.39 +3.18 0.0400 
Unassigned meiotic errors 28.89 2.37 +0.42 Not significant 
 Maternal age   Versus mean control age  
 n Mean SE Difference P value 
Control 70 28.47 0.73 – – 
MI, all 63 32.71 0.88 +4.24 0.0003 
MI, nullitransitional 33 30.73 1.04 +2.26 Not significant 
MI, transitional 30 34.90 1.36 +6.43 0.0001 
MII 38 28.29 1.18 –0.18 Not significant 
PZM 20 31.65 1.39 +3.18 0.0400 
Unassigned meiotic errors 28.89 2.37 +0.42 Not significant 

The mean paternal age for the entire sample was 32.99 years (n = 114, SE = 0.75).

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