DNA Polymorphism Analysis in Families with Recurrence of Free Trisomy 21

Constantinos G. Pangalos1, C. Conover Talbot, Jr.2, John G. Lewis2, Patricia A. Adelsberger2, Michael B. Petersen2, Jean-Louis Serre3, Marie-Odile Rethoré1, Marie-Christine de Blois1, Philippe Parent4, Albert A. Schinzel5, Franz Binkert5, Joelle Boue6, Elisabeth Corbin7, M. F. Croquette8, Simone Gilgenkrantz9, Jean de Grouchy10, M. F. Bertheas11, Marguerite Prieur1, Odile Raoul1, Francoise Serville12, J. P. Siffroi13, Francois Thepot14, Jerome Lejeune1, and Stylianos E. Antonarakis2

Am J. Hum. Genet. 51:1015-1027, 1992


Résumé :

Summary: We used DNA polymorphic markers on the long arm of human chromosome 21 in order to determine the parental and meiotic origin of the extra chromosome 21 in families with recurrent free trisomy 21. A total of 22 families were studied, 13 in which the individuals with trisomy 21 were siblings (category 1), four families in which the individuals with trisomy 21 were second-degree relatives (category 2), and five families in which the individuals with trisomy 21 were third-degree relatives, that is, their parents were siblings (category 3). In five category 1 families, parental mosaicism was detected, while in the remaining eight families, the origin of nondisjunction was maternal. In two of the four families of category 2 the nondisjunctions originated in individuals who were related. In only one of five category 3 families, the nondisjunctions originated in related individuals. These results suggest that parental mosaicism is an important etiologic factor in recurrent free trisomy 21 (5 of 22 families) and that chance alone can explain the recurrent trisomy 21 in many of the remaining families (14 of 22 families). However, in a small number of families (3 of 22), a familial predisposing factor or undetected mosaicism cannot be excluded.

Sommaire

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Introduction

Trisomy 21 is the most common known genetic cause of mental retardation. Free trisomy 21 accounts for approximately 95 % of cases (Giraud and Mattei 1975). Free trisomy 21 in more than one sibling occurs rarely; the recurrence risk in families with one affected child was estimated to be 1 % - 2 %, on the basis of empiric or prenatal data (Mikkelsen and Stene 1979; Daniel et al. 1982). The frequency of trisomy 21 in second-degree (uncle--aunt/nephew-niece combinations or third-degree (first cousins) relatives is not firmly established (Tamaren et al. 1983; Abuelo et al. 1986; Eunpu et al. 1986).

Possible explanations for the recurrence of free trisomy 21 in families include: (i) parental mosaicism, as has been reported by Harris et al. (1982), Uchida and Freeman (1985), and Nielsen et al. (1988); (ii) a genetic predisposition or factor that favors nondisjunction (for discussion of this hypothesis, see Alfi et al. 1980; Yokohama et al. 1981; De Voto et al. 1985); (iii) environmental predisposing factors, including hypothyroidism, toxins, etc. (Epstein 1989); (iv) the presence of double nucleolus organizing regions in acrocentric chromosomes (Jackson-Cook et al. 1985), however, this hypothesis has not been confirmed by other laboratories (Schwartz et al. 1989); and (v) chance alone.

Analysis of DNA polymorphisms on the long arm and the pericentromeric region of chromosome 21 in families with trisomy 21 can be used to establish the parental origin and meiotic stage of nondisjunction (Antonarakis et al. 1991, 1992; Sherman et al. 1991) in almost all families. The analysis of DNA polymorphism in the rare families with more than one individual affected with free trisomy 21 (47,+ 21) can provide valuable information far any possible genetic predisposing factor. In this paper we have collected and studied 22 families with more than one individual affected with free trisomy 21. The parental and meiotic origin of nondisjunction has been determined in all cases. The interpretation of the results is discussed below.

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Patients, Materials, and Methods

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Patients

A total of 22 families, each with more than one individual affected with free trisomy 21, were included in the study. Figure 1 shows the pedigrees of the families studied. The families were divided into the following three categories: (i) There were 12 nuclear families, each with two affected siblings (families RDS-01-RDS-O5, RDS-O7-RDS-11, RDS-13, and RDS-14) and one family (RDS-06) with three affected siblings. (ii) In four additional families (families RDS15-RDS-18), the individuals with trisomy 21 were second-degree relatives. They were all related through a male individual who was the father and sibling of the patients. (iii) In five families (families RDS-19-RDS-23), the individuals with trisomy 21 were third degree relatives, that is, they were offspring of siblings. The families of all three categories were collected from cytogenetic laboratories in France and Switzerland. The ages of mothers and fathers at the time of birth of each individual with Down syndrome are included in table 1.

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Cytogenetic Analysis

Chromosomal analysis of blood lymphocytes was performed on all individuals with trisomy 21 and on their parents. Chromosome banding was performed by the RHG or GTG technique (Dutrillaux and Lejeune 1971; Seabright 1971). In order to detect mosaicism, a total of 30 metaphases per individual with trisomy 21 were analyzed, as well as 200 metaphases in each of their parents. Mosaicism in our sample is defined as the presence of at least two trisomic cells in 200 metaphases examined. No cytogenetic heteromorphisms were studied since a considerable number of DNA polymorphisms were analyzed, including several pericentromeric markers (see below).

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DNA Polymorphism Analysis

The parental origin of the supernumerary chromosome 21 and the meiotic stage of the nondisjunction were detected by using DNA polymorphic markers. The following DNA polymorphisms were used after Southern blot hybridization (Southern 1975): D21S13, D21S110, D21S11, D21S8, D21S111, D21S82, D21S3, D21S112, D21S113, MX1, and COL6A1. Description of the probe-enzyme combinations, the detection method of these polymorphic markers and their mapping position on the long arm of human chromosome 21 can be found in Warren et al. (1989) and Petersen et al. (1991b). In addition, the following DNA polymorphisms were used after PCR amplification (Saiki et al. 1915) and detection of the alleles due to short sequence repeats (SSR) by PACE: D21S215 (21GT14) Warren et al. (1992), D21S120 (Burmeister et al. 1990), D21S192 (Van Camp et al. 1991), D21S213 (21-GTO5) and D21S212 (21-GT10) (A. C. Warren and S. E. Antonarakis, unpublished data), D21S210 (21-CT12) Warren et al. (1992), IFNAR (McInnis et al. 1991), D21S156 (Lewis et al. 1990), and HMG14 (Petersen et al. 1990). All of these polymorphisms are due to (GT)n dinucleotide repeats, except IFNAR, which is due to a (TAAA)n repeat in the poly(A) tail of an Alu sequence. Description of the detection method and the scoring of polymorphic alleles per family can be found elsewhere (Petersen et al. 1991a). Several of the markers used are considered pericentromeric in the long arm of the chromosome (Antonarakis et al. 1992). These markers are D21S215, D21S120, D21S13, D21S192, and D21S172. The last four markers show approximately 6 % recombination with a rare chromosome 21-specific polymorphism of alphoid sequences (Jabs et al. 1991), while marker D21S215 shows no recombination with the alphoid polymorphism (Warren et al. 1992). All pericentromeric markers can be used to determine the meiotic origin of nondisjunction. Not all the DNA markers were determined in all families.

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Results and Discussion

Table 1 presents the genotypes of the DNA polymorphisms examined in the members of all families. This table also presents the parental and meiotic origin of each trisomy 21 and the presence of crossovers in chromosomes 21 that participated in nondisjunction.

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Category I Families

There are 13 families that belong to the first category, in which the individuals with trisomy are siblings (preliminary analysis of families RDS-01 and RDS-02 has been described by Pangalos et al. 1988). Cytogenetic analysis showed that, in 3 of these 13 families, there was parental mosaicism in blood leukocytes. In families RDS-09 and RDS-10 there was a 2 % maternal mosaicism for trisomy 21 (46,XX/47,XX +21), while in family RDS-02 there was a 2 % paternal mosaicism for trisomy 21 (46,XY/47,XY + 21). Analysis of DNA polymorphisms confirmed that the parental origin of the trisomy 21 in individuals DS1 and DS2 of family RDS-02 and individual DS2 of family RDS-10 was from the parent with the mosaicism. Moreover, in family RDS-09, the DNA analysis revealed a chromosome 21 present in the individual with trisomy 21 that was not detected in the DNA of blood from either parent (see markers D21S82 and D21S112 in table 1 and D21S212 in table 1 and fig. 2), confirming the results from the cytogenetic analysis. Furthermore, analysis of DNA polymorphisms revealed potential mosaicism in two other families (RDS-13 and RDS-14) of this category, since polymorphic alleles for chromosome 21 markers found in the offspring with trisomy 21 were not present in the parents (see markers D21S156 for family RDS-13 and D21S112 for family RDS-14 in table 1; the mosaicism in family RDS-14 is probably maternal, since the "new" polymorphic allele for DNA marker D21S112 was not found in the paternal grandparents). Mosaicism that remains undetected by cytogenetic analysis can therefore be recognized after DNA analysis; however, there are cases in which mosaicism was only detected by cytogenetic analysis and was not confirmed by DNA analysis. Theoretically, mosaicism can never be detected by DNA analysis if the polymorphic alleles in the parental trisomic cells are identical.

It is of interest to note that the mosaic individuals in families RDS-09, RDS-13, and RDS-14 are probably themselves the products of meiotic nondisjunction, since they each have, in some of their cells, three different alleles at certain chromosome 21 loci tested. Far example, the data suggest that the mother in family RDS-09 contains, in some of her cells, alleles 2, 3, and 5, for polymorphic marker D21S212 (see table 1).

In summary, in the set of 13 nuclear families with two siblings with trisomy 21, we detected five cases (38 %) of parental mosaicism as the cause of the recurrence of trisomy 21. The mean maternal age for the first offspring with Down syndrome in these five families was 28.6 years, and the mean paternal age was 29.3 years. The presence of parental mosaicism for trisomy 21 has been previously shown to occur in families with more than one sibling with free trisomy 21 (Harris et a1.1982; Uchida and Freeman 1985; Nielsen et al. 1988). In those studies, the mean maternal age far the first offspring with Down syndrome in 11 families with more than one offspring with Down syndrome and parental mosaicism was 24.6 years.

In eight category 1 families, parental mosaicism was not detected. In these eight families there were 17 individuals with trisomy 21. The parental origin of the extra chromosome 21 in all 17 cases with Down syndrome was maternal. In all families (RDS-O1, RDS03--RDS-O8, and RDS-11 ), there was concordance of the parental origin of the trisomy 21 for the affected siblings. The mean maternal age for the first affected offspring in these eight families was 33.6 years, and the mean paternal age was 34.5 years. These ages are not different from the mean maternal or paternal ages in large series of families with trisomy 21. Analysis of pericentromeric DNA polymorphisms revealed that the nondisjunction had occurred in maternal meiosis I in 10 (58.8 %) of the 17 cases, while in 7 (41.2 %) of the 17 cases the error had occurred in maternal meiosis II. There is an excess of meiosis-II errors in this small sample compared with the observed 23 % among maternal meiosis errors in the study of 200 families with one child with free trisomy 21 (Antonarakis et al. 1992); however, the difference is not statistically significant (?2 = 2.48). In three families (RDS-03, RDS-06, and RDS-07), all offspring with Down syndrome were the result of meiosis I error, while in two families (RDS-04 and RDS-11) both offspring with Down syndrome were the result of meiosis II error. However, in the remaining three families (RDS-01, RDS-05, and RDS-08), the trisomy 21 in the first affected individual was due to meiosis I error, and the trisomy in the second affected individual was the result of meiosis II error. There are two families with affected DZ twins (or, in theory, polar-body twins). In one family (RDS-04) the trisomy 21 in both affected twins was due to maternal meiosis II errors. In the other family (RDS-08) the trisomy 21 in one affected twin was the result of maternal meiosis I error, while the trisomy 21 in the second affected twin originated from a maternal meiosis II error (see DNA marker D21S215 of table 1). In all seven cases with maternal meiosis II errors, crossovers have been observed in the chromosomes 21 that participated in nondisjunction. These results exclude the possibility of postzygotic (mitotic) error as the cause of these trisomies. In 9 of the 10 cases of maternal meiosis I errors in which enough DNA polymorphic markers on the long arm of chromosome 21 have been studied, crossovers have been observed in four cases, while in the remaining five cases no crossovers have been detected. This is in agreement with the proposed hypothesis of reduced recombination in meiosis I in trisomy 21 (Warren et al. 1987), which has been subsequently confirmed by Sherman et al. (1991) and Antonarakis et al. (1992).

In summary, in these eight families with two affected siblings and no paternal mosaicism, there is no apparent difference from the usual families with one affected child. We therefore presume that the recurrence of individuals with trisomy 21 in the same nuclear family is the result of chance alone. Assuming that the frequency of trisomy 21 in the population is 1/700 liveborn, we expect that 1/490 000 families with two children will have two affected individuals with trisomy 21 by chance. In conclusion, this study suggests that parental mosaicism is an important and frequent cause of recurrent trisomy 21 in nuclear families, since it has been found in about 40 % of the families; however chance alone accounts for the remaining 60 % of the families.

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Category 2 Families

In this category of four families, the individuals with Down syndrome are second-degree relatives. In all of these families the individuals with trisomy are related through a male individual (families RDS-15-RDS-18 of fig. 1). In families RDS-16 and RDS-17, the parental origin of nondisjunction in the Down syndrome of the third generation (designated "DS2" in the appropriate pedigrees in fig. 1) was maternal, and, therefore, the nondisjunction originated in unrelated individuals in those pedigrees. Data on the meiotic origin of nondisjunction in these families are included in table 1.

In families RDS-15 and RDS-18 the parental origin of nondisjunction in the Down syndrome of the third generation (designated DS3 for pedigree RIDS-15 and DS1 in pedigree RDS-18 in fig. 1) was paternal, and, therefore, the nondisjunction apparently originated in individuals in those pedigrees who were related. In these fathers (individuals "Fa" of pedigree RDS-15 and "Fa" of pedigree RDS-18 in fig. 1), no mosaicism has been observed either by cytogenetic or DNA analysis. The relationship of the origin of nondisjunction in families RDS-15 and RDS-18 can he attributed to chance alone; however, the fact that paternal nondisjunction for trisomy 21 is rare (about 5 %; Antonarakis et al. 1991; Sherman et al. 1991) in the general population suggests that these two families may be different from the ordinary families with trisomy 21. In family RDS-1 S, DNA polymorphism analysis ofpericentromeric markers showed that the paternal nondisjunction of individual DS3 occurred in the second meiotic division. Further analysis of DNA polymorphisms in 21q suggested that there was no recombination in the chromosomes that participated in nondisjunction. The presence of two chromosomes identical at all polymorphic loci analyzed that originate from one parent can be explained by (i) meiosis II error without a crossover event in the preceding meiosis I; (ii) paternal mosaicism that has not been discovered by the cytogenetic and DNA analysis, or (iii) mitotic error. In the last case the origin of trisomy 21 is somatic, involving the paternal chromosome. The paternal chromosome 21, which is present in two copies in individual DS3 of family RDS-15, is identical at the pericentromeric region to one of the grandmaternal chromosomes that participated in the maternal nondisjunction that causes trisomy 21 in the monozygotic twins DS1 and DS2. In family RD-18 the trisomy 21 in individual DS1 was due to an error in meiosis I in the paternal germ cells. DNA was not available from all members of this pedigree in order to study the nature of the chromosomes 21 that participated in the two nondisjunction events.

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Category 3 Families

In this category of five families, the individuals with Down syndrome are third-degree relatives, that is, their parents are siblings. In pedigrees RDS-19, RDS-22, and RDS-23 the parents of the individuals with Down syndrome are brothers and sisters, while in pedigrees RDS-20 and RDS-21, the parents of the individuals with Down syndrome are brothers (see fig. 1). In four pedigrees, namely RDS-20-RDS-23, the parents in which nondisjunction had occurred were not blood relatives, and, therefore, the occurrence of two individuals with Down syndrome in these extended pedigrees can be attributed to chance. In family RDS-19 the parents in whom nondisjunction had occurred were a brother and sister. The analysis of pericentromeric DNA markers in this pedigree showed that the error for individual DS1 was in maternal meiosis I, while for individual DS2 the error was in paternal meiosis II. A mitotic error in the latter case has been excluded, since crossover events have been detected in chromosomes 21 that participated in the paternal nondisjunction. Although a predisposing factor to nondisjunction cannot be excluded in this family, chance alone also can be the explanation of the recurrent Down syndrome. It is of interest that, among the nine individuals with Down syndrome studied in this category, there was an excess of paternally derived trisomy 21 (two of nine cases), but the sample is too small to derive any conclusions.

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Concluding Remarks

The aim of the study was to detect a possible genetic predisposing factor in trisomy 21. We therefore chose and collected 22 families with two affected individuals, in order to maximize the possibility of detecting such a genetic predisposition by using the powerful and unequivocal analysis of DNA markers on chromosome 21. With the exception of parental mosaicism in the relatively small sample studied, no other major genetic predisposing factor has been identified, and chance alone seems to be the main reason for the recurrence of free trisomy 1 within families.


Figure I. - Pedigrees of families with two or more individuals with free trisomy 21. Blackened squares indicate males affected with Down syndrome. Blackened circles indicate affected females. Unblackened squares and circles indicate unaffected males and females, respectively. Numbers inside unblackened symbols indicate total number of unaffected siblings. The diamond enclosing a square indicates a male fetus, and the diamond enclosing a circle indicates a female fetus. Small dots indicate abortuses or miscarriages, for which no other information is known. Fa = father; Mo = mother; DS = Down syndrome; NS = normal sibling. The abbreviations for the origin of the supernumerary chromosome 21 are as in the legend to table 1.


Figure 2. - Representative autoradiogram of the study of the origin of the extra chromosome 21 in individuals with Down syndrome. The alleles for DNA dinucleotide repeat marker D21S212 (21-GT10) are shown. The father (Fay) has alleles 1 and 2; the mother (Mo) shows alleles 3 and 4. The first offspring with Down syndrome (DS1) has alleles, 2, 3, and 5, while the second offspring with Down syndrome (DS2) has alleles 1, 3, and 5. Allele 5 comes from the mother, who cytogenetically shows mosaicism for trisomy 21.

Table I. - Families with recurrent Trisomy 21
Families ID N° Age of Father/Mother Parental origina Meiotic originb Cross-Over N° of crossovers DS relation Karyotype Alleles per marker at loci
D21S215b,c (21-gt14) D21S120b,c D21S13b,c (Taql) D21S13 (PCR) D21S192b,c D21S11010c,d
RDS-01
Fa15981222121112
Mo15991213121112
DS1160036/43MatM1No0Trisomy 21112123 M1122111
DS2 160138/45MatM2Yes1Trisomy 21222 M2112 M2111 M2111
RDS-02
Fa1602Pat Mos 2%232212
Mo1603131211
DS1 160434/28 Pat MosTrisomy 21333 P122111
DS2 160540/34 Pat MosTrisomy 21122 P122122 P
NS1 16061211
RDS-03
Fa1607231212
Mo1608121211
DS1160948/38Mat M1No 0Trisomy 21123 M1122111
DS2161054/44 Mat M1 Yes1Trisomy 21122 Ml112112
NS1611132211
RDS-04
Fa16121211
Mo16131212
DS1161432/31 Mat M2 Yes1Trisomy 21222 M2112 nr
DS2 161532/31 Mat M2 Yes1Trisomy 21222 M2122 M r
RDS-05
Fa1616122212
Mo1617231211
DS1161828122 Mat M1 No0Trisomy 21123 M1122 M1112
DS2161935/29 Mat M2Yes1Trisomy 21122 M2112 M2112
NS11621221211
NS21620121211
NS31622221211
RDS-06
Fa16232222
Mo16241211
DS1162525/24MatM1No0Trisomy 21122 M1112 M
DS2162630/29 Mat M1Yes1Trisomy 21122 M1112 M
DS3162736/35 Mat M1Yes1Trisomy 21122 M1112 M
NS116281212
RDS-07
[Fa][?2][12][?1]
Mo1629132211
DS1163036/36Mat M1No0Trisomy 21123 M1122111
DS2163144/44 Mat M1Yes1Trisomy 21123 M1122111
NS11632122211
NS21633232211
NS31634232211
RDS-08
Fa1612231211
Mo1613122211
DS1161430/36MatM1No0Trisomy 21 123 M1222111
DS2161530/36MatM2Yes1Trisomy 21222 M2222111
RDS-09
Fa2218122212
Mo2219Mat Mos 2%231211
DS1222023/26Mat MosTrisomy 21123122111
DS2222126/29 Mat MosTrisomy 21123122111
RDS-10
Fa325412122212
Mo3255Mat Mos 2%13221211
DS1325630/28Trisomy 21123 122122111
DS2325734/32Mat MosTrisomy 21133 M122122
RDS-11
Fa3258122211
[Mo][?2][12][?1]
DS13259 41/39MatM2Yes2Trisomy 21122222 M2111
DS2326044/42 Mat M2 Yes1Trisomy 21222222 M211
NS13261221211
NS23262121211
NOTE.-DNA polymorphism analysis of members of families with recurrent free trisomy 21. The individuals studied correspond to members of the pedigrees shown in figure 1. The DNA polymorphic markers studied have been arranged from left to right, from the more centromeric to the most telomeric (the order of the polymorphic loci has been determined in Petersen et al. (1991) and by S, E. Antonarakis and A. Chakravarti, unpublished linkage map). Informative data are printed in boldface type. Alleles in brackets are those inferred from the other data in the family. The meiotic origin of the extra chromosome 21 using pericentromeric DNA markers was often established, given the parental origin determined, by using the results from ether markers (e.g., in family RDS-03 the meiotic origin of the extra chromosome 21 in individual DS1 was assigned as maternal meiosis I error since the parental origin of nondisjunction was maternal, as determined by markers D21S82 and D21S112).

a. Mat = Maternal; Pat = paternal; Mos = mosaicism.

b. M1 = Maternal meiosis I error; M2 = maternal meiosis II error; P1 = paternal meiosis I error; P2 = paternal meiosis II error.

c. M - Maternal origin of the extra chromosome 21; P = paternal origin of the extra chromosome 21.

d. nr = Nonreduction to homozygosity; r = reduction to homozygosity.

e. The meiotic origin of nondisjunction was determined by haplotyping pericentromeric polymorphism.

Families ID N° Alleles per marker at loci
D21S115c,d D21S8c,d D21S210c,d (21-gt12) D21S111c,d D21S213d 21-gt05) D21S82a,c,d IFNARc,d D21S3c,d D21S156a,c,d HMG14c,d MX1c,d D21S212a,c,d (21-gt10) D21S113d D21S112a,c,d COL6A1c,d
RDS-01
Fa15981111231112111211
Mo15992212132212123311
DS11600122 M112 nr123 nr122 M112112 nr133 M111
DS2 1601122 M112 nr133 nr122 M112 nr133 M111
RDS-02
Fa1602121211221211121211
Mo1603221122331212132311
DS1 1604222122 P112 P223 P122111111222111
DS2 1605112 P122 P112 P223 P222112113223111
NS1 160622112233 ?11132311
RDS-03
Fa1607221112221112121211
Mo1608221112131222233411
DS11609222111122123 M nr112 nr122223 nr234 M nr111
DS21610222111112123 M nr112 nr122 223 nr233 M r111
NS16112211221222121311
RDS-04
Fa16121212231211122224111211
Mo16131212231212342213111311
DS11614122122223122112 nr134 M nr222134 M nr111113 nr111
DS2 1615122111 r233111 r122 M r133 M r222134 M nr111113 nr111
RDS-05
Fa161612111112121312
Mo161711111312121234
DS11618111111113 nr122122112 nr134 M nr
DS21619111111133 M r112122123 nr134 M nr
NS1162112111122121123
NS2162011111311122314
NS3162212111311121114
RDS-06
Fa1623121212222212111212
Mo1624112212222222223423
DS11625111122112222222222122 M234 M nr223 nr
DS21626112222112222222222122 M233 M r222 r
DS31627112222112222222222122 M244 M r233 M r
NS116281112222212121413
RDS-07
[Fa][?1][?1][?2][12][?2][14][12][12)
Mo16291111221212233412
DS11630111111222122123 M nr234 M nr112
DS21631111111222222 r222 r122 M r133 M r112
NS116321111221112341422
NS216331111222222122311
NS316341111221112341422
RDS-08
Fa1612121112232212121211
Mo1613121122221211113413
DS11614112111222222122 nr112111234 M nr113 nr
DS21615122111122223122 nr111234 M nr113 nr
RDS-09
Fa221811121212121211
Mo221911111212343412
DS12220111112123 Mos122235 Mos135 Mos111
DS22221111112112112135 Mos235 Mos111
RDS-10
Fa325412122322122311
Mo325512131222121311
DS13256122122123123222112123111
DS23257122122123123222333111
RDS-11
Fa3258121312121111111224
[Mo][?1][?2][23][13][?1][?1][?1][34][13]
DS13259 122122 M123 nr123 nr111111111133 M r112 M r
DS23260111223 M223 nr113 nr111111111234 M nr134 M nr
NS13261122313121111111312
NS23262121213121111111312
Table I. - (continued)
Families ID N° Age of Father/Mother Parental origina Meiotic originb Cross-Over N° of crossovers DS relation Karyotype Alleles per marker at loci
D21S215b,c (21-gt14) D21S120b,c D21S13b,c (Taql) D21S13 (PCR) D21S192b,c D21S11010c,d
RDS-13
DS1326625/25Mat MosTrisomy 21112122
[Fa1]
Mo32641212
Fa232631211
DS2326529/29Mat MosTrisomy 21122122
RDS-14
Fa3301121211
Mo3300222311
DS1329930/36Mat MosTrisomy 21122123111
DS2358432/38Mat MosTrisomy 21122111
PGFa3916
PGMo3915
MoSib3917
RDS-15
GFa163922131211
GMo16401223221211
DS1164133/27MatM1No0Trisomy 21122 M1123 M1222112 M112
DS2164233/27MatM1No0Trisomy 21122 M1123 M1222112 M1112 nr
Fa1643333322[12]112 nr
Mo16441212121212
DS3164533/33PatP2No0RelatedTrisomy 21233 P233 P122222 P2122
RDS-16
[GFa][?1][13]
GMo164611111212
DS1164742/39PatP1No0Trisomy 21111113 P1122112122
Fa16481113221211
Mo16491212121111
DS2165039/33MatM1Yes2UnrelatedTrisomy 21112 M1112 M1122 M1112111
NS116511113221111
NS216521113221111
RDS-17
[GFa][12][1?][2][2][12](12]
GMo1662221211121122
DS11663??/38MatM1eTrisomy 21122112112122112222
NS11664221112221112
Fa1665221212121112
Mo1666221312222211
DS2166733/32MatM1No0UnrelatedTrisomy 21222123 M1112122122 M112
NS21668221112221211
RDS-18
Fa32731212
Mo32721112
DS1327441/39PatP1Yes1RelatedTrisomy 21112 P1112
NS132711212
RDS-19
Fa13275232212
Mo13276142211
DS1327745/37MatM1No0Trisomy 21134 M1222112
Fa23278142211
Mo23279242212
DS2328042/39PatP2Yes2RelatedTrisomy 21112 P2222111
RDS-20
Fa13799241112
Mo13800221333
DS1380133/23MatM1No0Trisomy 21224113 M1133 M
NS13805221123
Fa23802132211
Mo23803221113
DS2380435/36MatM1Yes1UnrelatedTrisomy 21122 M112 M113 M1
NS23806231213
RDS-21
GMo16532311
Fa11654232312
Mo11655221211
DS1165627/25MatM2Yes1Trisomy 21222112 M2111
NS116572312
Fa21658131211
Mo21659231211
DS2166026/22MatM2Yes2UnrelatedTrisomy 21223 M2112111
NS2166111
RDS-22
Fa13608123422
Mo13607221424
DS1360624/24MatM1Yes3Trisomy 21222144 M1224 M1
Fa23611332313
Mo23610123422
DS2360923/27PatP2Yes1UnrelatedTrisomy 21133 P223 P2233 P2
RDS-23
Fa32842211
Mo32851211
DS1328637/30MatM1Yes1UnrelatedTrisomy 21122 M1111
Families ID N° Alleles per marker at loci
D21S115c,d D21S8c,d D21S210c,d (21-gt12) D21S111c,d D21S213d 21-gt05) D21S82a,c,d IFNARc,d D21S3c,d D21S156a,c,d HMG14c,d MX1c,d D21S212a,c,d (21-gt10) D21S113d D21S112a,c,d COL6A1c,d
RDS-13
DS13266112222145 M Mos113112112111244
[Fa1][?2][?3][?1][?2]
Mo32641222141122121214
Fa232631123231212123412
DS23265112222125 M Mos112122122124 M114
RDS-14
Fa33011212221213122215
Mo3300231213221223123 M24
DS13299133 M122112 M122122 M133 M123 M134 Mos
DS23584223112123 M222124 M
PGFa391615
PGMo391516
MoSib391726
RDS-15
GFa163911111222331112
GMo164011121212121233
DS11641111112 nr122122 nr123 M nr112 nr234 nr133 M123 nr
DS21642111112 nr122122 nr123 M nr112 nr234 nr133 M123 nr
Fa16411112[23][?1]2313
Mo1644111111331411154512
DS31645111111111113 P r122 P r111335 P r334 P r111
RDS-16
[GFa][1][23]
GMo16461111112312232311
DS11647111111111223122123 nr123 nr123 P nr
Fa16481111111312121323
Mo16491111121312[34]45
DS21650111111112 nr333 r112134 M nr145 nr233
NS116511111111312131433
NS216521111111312131433
RDS-17
[GFa][2][12][3][2][1][14][1]
GMo16621211121211232312
DS11663122112122112112123 nr123 M nr122
NS116642211231212133411
Fa16651211131212131322
Mo16661212131222115634
DS21667112112 nr113122113356 M nr234 M nr
NS216682212332212133524
RDS-18
Fa32731223121212232212123
Mo3272222313341211122313
DS13274122 nr223123 nr124 P nr112123 P nr222123 nr223 P r
NS13271122212231212221312
RDS-19
Fa13275112213132214123412
Mo13276122224122234111211
DS13277112 nr222124 M nr112 nr222344 nr112124 M nr111
Fa23278122244142234122312
Mo23279121211451212231423
DS23280122222144 P115 P r122234 P nr123 nr123 P nr112 P r
RDS-20
Fa1379912121123221122
Mo1380013111211131213
DS13801113 nr111112 nr112 M123 M nr112 nr123 M nr
NS1380512111213121112
Fa2380211121123241212
Mo2380314221114223423
DS23804114 nr222111112 M r222144 M r222 r
NS2380614121113241322
RDS-21
GMo1653121212232211441313
Fa11654111122232212221213
Mo11655121112121122352423
DS11656122 M r111122 nr123 nr112 M222235 M nr224 nr123 nr
NS11657111222 1121222232412
Fa21658121212232211442311
Mo21659111112111211161512
DS21660112112111 r112 M122 nr111146 M nr125 M nr122 M r
NS216611111121322114612
RDS-22
Fa13608111211231211
Mo13607231223131323
DS13606123 M nr112133 M r133 nr123 nr133 M r
Fa23611221212121422
Mo23610121322342212
DS23609122112 nr122 nr124 P nr124 P nr122
RDS-23
Fa328411121122121411
Mo328512341211132312
DS13286112 nr234 m nr112 nr112 M112 r122 M r122 M r

Haut

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