Haut
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.
Haut
Patients, Materials, and MethodsHaut
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.
Haut
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).
Haut
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.
Haut
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.
Haut
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.
Haut
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.
Haut
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.
Haut
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 |
Fa | 1598 | | | | | | | | 12 | 22 | 12 | | 11 | 12 |
Mo | 1599 | | | | | | | | 12 | 13 | 12 | | 11 | 12 |
DS1 | 1600 | 36/43 | Mat | M1 | No | 0 | | Trisomy
21 | 112 | 123 M1 | 122 | | 111 | |
DS2
| 1601 | 38/45 | Mat | M2 | Yes | 1 | | Trisomy
21 | 222 M2 | 112 M2 | 111
M2 | | 111 | |
RDS-02 |
Fa | 1602 | | | | | | Pat Mos
2% | 23 | | 22 | | | | 12 |
Mo | 1603 | | | | | | | | 13 | | 12 | | | 11 |
DS1 | 1604 | 34/28 | Pat
Mos | | | | | Trisomy 21 | 333
P | | 122 | | | 111 |
DS2 | 1605 | 40/34 | Pat
Mos | | | | | Trisomy 21 | 122
P | | 122 | | | 122 P |
NS1
| 1606 | | | | | | | | | | 12 | | | 11 |
RDS-03 |
Fa | 1607 | | | | | | | | 23 | | 12 | | | 12 |
Mo | 1608 | | | | | | | | 12 | | 12 | | | 11 |
DS1 | 1609 | 48/38 | Mat
| M1 | No | 0 | | Trisomy 21 | 123
M1 | | 122 | | | 111 |
DS2 | 1610 | 54/44 | Mat | M1
| Yes | 1 | | Trisomy 21 | 122
Ml | | 112 | | | 112 |
NS | 1611 | | | | | | | | 13 | | 22 | | | 11 |
RDS-04 |
Fa | 1612 | | | | | | | | | | 12 | | | 11 |
Mo | 1613 | | | | | | | | | | 12 | | | 12 |
DS1 | 1614 | 32/31 | Mat | M2
| Yes | 1 | | Trisomy
21 | | | 222 M2 | | | 112 nr |
DS2 | 1615 | 32/31 | Mat | M2
| Yes | 1 | | Trisomy
21 | | | 222 M2 | | | 122 M r |
RDS-05 |
Fa | 1616 | | | | | | | | 12 | | 22 | | | 12 |
Mo | 1617 | | | | | | | | 23 | | 12 | | | 11 |
DS1 | 1618 | 28122 | Mat | M1
| No | 0 | | Trisomy 21 | 123
M1 | | 122 M1 | | | 112 |
DS2 | 1619 | 35/29 | Mat
| M2 | Yes | 1 | | Trisomy 21 | 122
M2 | | 112 M2 | | | 112 |
NS1 | 1621 | | | | | | | | 22 | | 12 | | | 11 |
NS2 | 1620 | | | | | | | | 12 | | 12 | | | 11 |
NS3 | 1622 | | | | | | | | 22 | | 12 | | | 11 |
RDS-06 |
Fa | 1623 | | | | | | | | | | 22 | | | 22 |
Mo | 1624 | | | | | | | | | | 12 | | | 11 |
DS1 | 1625 | 25/24 | Mat | M1 | No | 0 | | Trisomy
21 | | | 122 M1 | | | 112 M |
DS2 | 1626 | 30/29 | Mat
| M1 | Yes | 1 | | Trisomy
21 | | | 122 M1 | | | 112 M |
DS3 | 1627 | 36/35 | Mat
| M1 | Yes | 1 | | Trisomy
21 | | | 122 M1 | | | 112 M |
NS1 | 1628 | | | | | | | | | | 12 | | | 12 |
RDS-07 |
[Fa] | | | | | | | | | [?2] | | [12] | | | [?1] |
Mo | 1629 | | | | | | | | 13 | | 22 | | | 11 |
DS1 | 1630 | 36/36 | Mat
| M1 | No | 0 | | Trisomy 21 | 123
M1 | | 122 | | | 111 |
DS2 | 1631 | 44/44 | Mat
| M1 | Yes | 1 | | Trisomy 21 | 123
M1 | | 122 | | | 111 |
NS1 | 1632 | | | | | | | | 12 | | 22 | | | 11 |
NS2 | 1633 | | | | | | | | 23 | | 22 | | | 11 |
NS3 | 1634 | | | | | | | | 23 | | 22 | | | 11 |
RDS-08 |
Fa | 1612 | | | | | | | | 23 | | 12 | | | 11 |
Mo | 1613 | | | | | | | | 12 | | 22 | | | 11 |
DS1 | 1614 | 30/36 | Mat | M1 | No | 0 | | Trisomy
21 | 123 M1 | | 222 | | | 111 |
DS2 | 1615 | 30/36 | Mat | M2 | Yes | 1 | | Trisomy
21 | 222 M2 | | 222 | | | 111 |
RDS-09 |
Fa | 2218 | | | | | | | | 12 | | 22 | | | 12 |
Mo | 2219 | | | | | | | Mat
Mos 2% | 23 | | 12 | | | 11 |
DS1 | 2220 | 23/26 | Mat
Mos | | | | | Trisomy
21 | 123 | | 122 | | | 111 |
DS2 | 2221 | 26/29 | Mat
Mos | | | | | Trisomy
21 | 123 | | 122 | | | 111 |
RDS-10 |
Fa | 3254 | | | | | | | | 12 | 12 | 22 | | | 12 |
Mo | 3255 | | | | | | | Mat
Mos 2% | 13 | 22 | 12 | | | 11 |
DS1 | 3256 | 30/28 | | | | | | Trisomy
21 | 123 | 122 | 122 | | | 111 |
DS2 | 3257 | 34/32 | Mat
Mos | | | | | Trisomy 21 | 133
M | 122 | 122 | | | |
RDS-11 |
Fa | 3258 | | | | | | | | 12 | | 22 | | | 11 |
[Mo] | | | | | | | | | [?2] | | [12] | | | [?1] |
DS1 | 3259
| 41/39 | Mat | M2 | Yes | 2 | | Trisomy
21 | 122 | | 222 M2 | | | 111 |
DS2 | 3260 | 44/42 | Mat | M2
| Yes | 1 | | Trisomy
21 | 222 | | 222 M2 | | | 11 |
NS1 | 3261 | | | | | | | | 22 | | 12 | | | 11 |
NS2 | 3262 | | | | | | | | 12 | | 12 | | | 11 |
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 |
Fa | 1598 | 11 | 11 | | | | 23 | | 11 | | | | 12 | 11 | 12 | 11 |
Mo | 1599 | 22 | 12 | | | | 13 | | 22 | | | | 12 | 12 | 33 | 11 |
DS1 | 1600 | 122 M | 112
nr | | | | 123 nr | | 122
M | | | | 112 | 112 nr | 133
M | 111 |
DS2 | 1601 | 122 M | 112
nr | | | | 133 nr | | 122
M | | | | | 112 nr | 133
M | 111 |
RDS-02 |
Fa | 1602 | 12 | 12 | | 11 | | 22 | | 12 | | | 11 | 12 | | 12 | 11 |
Mo | 1603 | 22 | 11 | | 22 | | 33 | | 12 | | | 12 | 13 | | 23 | 11 |
DS1 | 1604 | 222 | 122
P | | 112 P | | 223
P | | 122 | | | 111 | 111 | | 222 | 111 |
DS2 | 1605 | 112 P | 122
P | | 112 P | | 223
P | | 222 | | | 112 | 113 | | 223 | 111 |
NS1
| 1606 | 22 | 11 | | 22 | | 33
? | | 11 | | | | 13 | | 23 | 11 |
RDS-03 |
Fa | 1607 | 22 | 11 | | 12 | | 22 | | 11 | | | 12 | 12 | | 12 | 11 |
Mo | 1608 | 22 | 11 | | 12 | | 13 | | 12 | | | 22 | 23 | | 34 | 11 |
DS1 | 1609 | 222 | 111 | | 122 | | 123
M nr | | 112 nr | | | 122 | 223
nr | | 234 M nr | 111 |
DS2 | 1610 | 222 | 111 | | 112 | | 123
M nr | | 112 nr | | | 122 | 223
nr | | 233 M r | 111 |
NS | 1611 | 22 | 11 | | 22 | | 12 | | | | | 22 | 12 | | 13 | 11 |
RDS-04 |
Fa | 1612 | 12 | 12 | | | | 23 | | 12 | 11 | 12 | 22 | 24 | 11 | 12 | 11 |
Mo | 1613 | 12 | 12 | | | | 23 | | 12 | 12 | 34 | 22 | 13 | 11 | 13 | 11 |
DS1 | 1614 | 122 | 122 | | | | 223 | | 122 | 112
nr | 134 M nr | 222 | 134 M nr | 111 | 113
nr | 111 |
DS2 | 1615 | 122 | 111
r | | | | 233 | | 111 r | 122 M
r | 133 M r | 222 | 134 M nr | 111 | 113
nr | 111 |
RDS-05 |
Fa | 1616 | 12 | 11 | | | | 11 | | 12 | | | 12 | 13 | | 12 | |
Mo | 1617 | 11 | 11 | | | | 13 | | 12 | | | 12 | 12 | | 34 | |
DS1 | 1618 | 111 | 111 | | | | 113
nr | | 122 | | | 122 | 112
nr | | 134 M nr | |
DS2 | 1619 | 111 | 111 | | | | 133
M r | | 112 | | | 122 | 123
nr | | 134 M nr | |
NS1 | 1621 | 12 | 11 | | | | 11 | | 22 | | | 12 | 11 | | 23 | |
NS2 | 1620 | 11 | 11 | | | | 13 | | 11 | | | 12 | 23 | | 14 | |
NS3 | 1622 | 12 | 11 | | | | 13 | | 11 | | | 12 | 11 | | 14 | |
RDS-06 |
Fa | 1623 | 12 | 12 | | 12 | | 22 | | 22 | | | 12 | 11 | | 12 | 12 |
Mo | 1624 | 11 | 22 | | 12 | | 22 | | 22 | | | 22 | 22 | | 34 | 23 |
DS1 | 1625 | 111 | 122 | | 112 | | 222 | | 222 | | | 222 | 122
M | | 234 M nr | 223 nr |
DS2 | 1626 | 112 | 222 | | 112 | | 222 | | 222 | | | 222 | 122
M | | 233 M r | 222 r |
DS3 | 1627 | 112 | 222 | | 112 | | 222 | | 222 | | | 222 | 122
M | | 244 M r | 233 M r |
NS1 | 1628 | 11 | | | 12 | | 22 | | 22 | | | 12 | 12 | | 14 | 13 |
RDS-07 |
[Fa] | | [?1] | [?1] | | | | [?2] | | [12] | | | [?2] | [14] | | [12] | [12) |
Mo | 1629 | 11 | 11 | | | | 22 | | 12 | | | 12 | 23 | | 34 | 12 |
DS1 | 1630 | 111 | 111 | | | | 222 | | | | | 122 | 123
M nr | | 234 M nr | 112 |
DS2 | 1631 | 111 | 111 | | | | 222 | | 222
r | | | 222 r | 122 M r | | 133 M
r | 112 |
NS1 | 1632 | 11 | 11 | | | | 22 | | 11 | | | 12 | 34 | | 14 | 22 |
NS2 | 1633 | 11 | 11 | | | | 22 | | 22 | | | 22 | 12 | | 23 | 11 |
NS3 | 1634 | 11 | 11 | | | | 22 | | 11 | | | 12 | 34 | | 14 | 22 |
RDS-08 |
Fa | 1612 | 12 | 11 | | 12 | | 23 | | 22 | | | 12 | 12 | | 12 | 11 |
Mo | 1613 | 12 | 11 | | 22 | | 22 | | 12 | | | 11 | 11 | | 34 | 13 |
DS1 | 1614 | 112 | 111 | | 222 | | 222 | | 122
nr | | | 112 | 111 | | 234 M
nr | 113 nr |
DS2 | 1615 | 122 | 111 | | 122 | | 223 | | 122
nr | | | | 111 | | 234 M nr | 113
nr |
RDS-09 |
Fa | 2218 | 11 | | | 12 | | 12 | | | | | 12 | 12 | | 12 | 11 |
Mo | 2219 | 11 | | | 11 | | 12 | | | | | 12 | 34 | | 34 | 12 |
DS1 | 2220 | 111 | | | 112 | | 123
Mos | | | | | 122 | 235
Mos | | 135 Mos | 111 |
DS2 | 2221 | 111 | | | 112 | | 112 | | | | | 112 | 135
Mos | | 235 Mos | 111 |
RDS-10 |
Fa | 3254 | 12 | | | | | | | | 12 | 23 | 22 | | 12 | 23 | 11 |
Mo | 3255 | 12 | | | | | | | | 13 | 12 | 22 | | 12 | 13 | 11 |
DS1 | 3256 | 122 | | | | | | 122 | | 123 | 123 | 222 | | 112 | 123 | 111 |
DS2 | 3257 | 122 | | | | | | 122 | | 123 | 123 | 222 | | | 333 | 111 |
RDS-11 |
Fa | 3258 | 12 | | | | | 13 | | | 12 | 12 | 11 | 11 | 11 | 12 | 24 |
[Mo] | | [?1] | | | | | [?2] | | | [23] | [13] | [?1] | [?1] | [?1] | [34] | [13] |
DS1 | 3259
| 122 | | | | | 122
M | | | 123 nr | 123
nr | 111 | 111 | 111 | 133 M r | 112 M r |
DS2 | 3260 | 111 | | | | | 223
M | | | 223 nr | 113
nr | 111 | 111 | 111 | 234 M nr | 134 M nr |
NS1 | 3261 | 12 | | | | | 23 | | | 13 | 12 | 11 | 11 | 11 | 13 | 12 |
NS2 | 3262 | 12 | | | | | 12 | | | 13 | 12 | 11 | 11 | 11 | 13 | 12 |
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 |
DS1 | 3266 | 25/25 | Mat
Mos | | | | | Trisomy
21 | | | 112 | | | 122 |
[Fa1] | | | | | | | | | | | | | | |
Mo | 3264 | | | | | | | | | | 12 | | | 12 |
Fa2 | 3263 | | | | | | | | | | 12 | | | 11 |
DS2 | 3265 | 29/29 | Mat
Mos | | | | | Trisomy
21 | | | 122 | | | 122 |
RDS-14 |
Fa | 3301 | | | | | | | | 12 | 12 | 11 | | | |
Mo | 3300 | | | | | | | | 22 | 23 | 11 | | | |
DS1 | 3299 | 30/36 | Mat
Mos | | | | | Trisomy
21 | 122 | 123 | 111 | | | |
DS2 | 3584 | 32/38 | Mat
Mos | | | | | Trisomy
21 | 122 | | 111 | | | |
PGFa | 3916 | | | | | | | | | | | | | |
PGMo | 3915 | | | | | | | | | | | | | |
MoSib | 3917 | | | | | | | | | | | | | |
RDS-15 |
GFa | 1639 | | | | | | | | 22 | 13 | 12 | | 11 | |
GMo | 1640 | | | | | | | | 12 | 23 | 22 | | 12 | 11 |
DS1 | 1641 | 33/27 | Mat | M1 | No | 0 | | Trisomy
21 | 122 M1 | 123 M1 | 222 | | 112
M1 | 12 |
DS2 | 1642 | 33/27 | Mat | M1 | No | 0 | | Trisomy
21 | 122 M1 | 123 M1 | 222 | | 112
M1 | 112 nr |
Fa | 1643 | | | | | | | | 33 | 33 | 22 | | [12] | 112
nr |
Mo | 1644 | | | | | | | | 12 | 12 | 12 | | 12 | 12 |
DS3 | 1645 | 33/33 | Pat | P2 | No | 0 | Related | Trisomy
21 | 233 P | 233 P | 122 | | 222
P2 | 122 |
RDS-16 |
[GFa] | | | | | | | | | [?1] | [13] | | | | |
GMo | 1646 | | | | | | | | 11 | 11 | 12 | | | 12 |
DS1 | 1647 | 42/39 | Pat | P1 | No | 0 | | Trisomy
21 | 111 | 113 P1 | 122 | | 112 | 122 |
Fa | 1648 | | | | | | | | 11 | 13 | 22 | | 12 | 11 |
Mo | 1649 | | | | | | | | 12 | 12 | 12 | | 11 | 11 |
DS2 | 1650 | 39/33 | Mat | M1 | Yes | 2 | Unrelated | Trisomy
21 | 112 M1 | 112 M1 | 122
M1 | | 112 | 111 |
NS1 | 1651 | | | | | | | | 11 | 13 | 22 | | 11 | 11 |
NS2 | 1652 | | | | | | | | 11 | 13 | 22 | | 11 | 11 |
RDS-17 |
[GFa] | | | | | | | | | [12] | [1?] | [2] | [2] | [12] | (12] |
GMo | 1662 | | | | | | | | 22 | 12 | 11 | 12 | 11 | 22 |
DS1 | 1663 | ??/38 | Mat | M1e | | | | Trisomy
21 | 122 | 112 | 112 | 122 | 112 | 222 |
NS1 | 1664 | | | | | | | | 22 | 11 | 12 | 22 | 11 | 12 |
Fa | 1665 | | | | | | | | 22 | 12 | 12 | 12 | 11 | 12 |
Mo | 1666 | | | | | | | | 22 | 13 | 12 | 22 | 22 | 11 |
DS2 | 1667 | 33/32 | Mat | M1 | No | 0 | Unrelated | Trisomy
21 | 222 | 123 M1 | 112 | 122 | 122
M | 112 |
NS2 | 1668 | | | | | | | | 22 | 11 | 12 | 22 | 12 | 11 |
RDS-18 |
Fa | 3273 | | | | | | | | 12 | | 12 | | | |
Mo | 3272 | | | | | | | | 11 | | 12 | | | |
DS1 | 3274 | 41/39 | Pat | P1 | Yes | 1 | Related | Trisomy
21 | 112 P1 | | 112 | | | |
NS1 | 3271 | | | | | | | | 12 | | 12 | | | |
RDS-19 |
Fa1 | 3275 | | | | | | | | 23 | | 22 | | | 12 |
Mo1 | 3276 | | | | | | | | 14 | | 22 | | | 11 |
DS1 | 3277 | 45/37 | Mat | M1 | No | 0 | | Trisomy
21 | 134 M1 | | 222 | | | 112 |
Fa2 | 3278 | | | | | | | | 14 | | 22 | | | 11 |
Mo2 | 3279 | | | | | | | | 24 | | 22 | | | 12 |
DS2 | 3280 | 42/39 | Pat | P2 | Yes | 2 | Related | Trisomy
21 | 112 P2 | | 222 | | | 111 |
RDS-20 |
Fa1 | 3799 | | | | | | | | 24 | 11 | | | 12 | |
Mo1 | 3800 | | | | | | | | 22 | 13 | | | 33 | |
DS1 | 3801 | 33/23 | Mat | M1 | No | 0 | | Trisomy
21 | 224 | 113 M1 | | | 133 M | |
NS1 | 3805 | | | | | | | | 22 | 11 | | | 23 | |
Fa2 | 3802 | | | | | | | | 13 | 22 | | | 11 | |
Mo2 | 3803 | | | | | | | | 22 | 11 | | | 13 | |
DS2 | 3804 | 35/36 | Mat | M1 | Yes | 1 | Unrelated | Trisomy
21 | 122 M | 112 M | | | 113 M1 | |
NS2 | 3806 | | | | | | | | 23 | 12 | | | 13 | |
RDS-21 |
GMo | 1653 | | | | | | | | 23 | | | | | 11 |
Fa1 | 1654 | | | | | | | | 23 | 23 | | | | 12 |
Mo1 | 1655 | | | | | | | | 22 | 12 | | | | 11 |
DS1 | 1656 | 27/25 | Mat | M2 | Yes | 1 | | Trisomy
21 | 222 | 112 M2 | | | | 111 |
NS1 | 1657 | | | | | | | | 23 | | | | | 12 |
Fa2 | 1658 | | | | | | | | 13 | 12 | | | | 11 |
Mo2 | 1659 | | | | | | | | 23 | 12 | | | | 11 |
DS2 | 1660 | 26/22 | Mat | M2 | Yes | 2 | Unrelated | Trisomy
21 | 223 M2 | 112 | | | | 111 |
NS2 | 1661 | | | | | | | | | | | | | 11 |
RDS-22 |
Fa1 | 3608 | | | | | | | | 12 | 34 | | | 22 | |
Mo1 | 3607 | | | | | | | | 22 | 14 | | | 24 | |
DS1 | 3606 | 24/24 | Mat | M1 | Yes | 3 | | Trisomy
21 | 222 | 144 M1 | | | 224 M1 | |
Fa2 | 3611 | | | | | | | | 33 | 23 | | | 13 | |
Mo2 | 3610 | | | | | | | | 12 | 34 | | | 22 | |
DS2 | 3609 | 23/27 | Pat | P2 | Yes | 1 | Unrelated | Trisomy
21 | 133 P | 223 P2 | | | 233 P2 | |
RDS-23 |
Fa | 3284 | | | | | | | | | | 22 | | | 11 |
Mo | 3285 | | | | | | | | | | 12 | | | 11 |
DS1 | 3286 | 37/30 | Mat | M1 | Yes | 1 | Unrelated | Trisomy
21 | | | 122 M1 | | | 111 |
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 |
DS1 | 3266 | 112 | | | | | 222 | | | 145
M Mos | 113 | 112 | | 112 | 111 | 244 |
[Fa1] | | | | | | | [?2] | | | | [?3] | | | | [?1] | [?2] |
Mo | 3264 | 12 | | | | | 22 | | | 14 | 11 | 22 | | 12 | 12 | 14 |
Fa2 | 3263 | 11 | | | | | 23 | | | 23 | 12 | 12 | | 12 | 34 | 12 |
DS2 | 3265 | 112 | | | | | 222 | | | 125
M Mos | 112 | 122 | | 122 | 124
M | 114 |
RDS-14 |
Fa | 3301 | | | 12 | | 12 | 22 | 12 | | 13 | 12 | | 22 | | 15 | |
Mo | 3300 | | | 23 | | 12 | 13 | 22 | | 12 | 23 | | 123
M | | 24 | |
DS1 | 3299 | | | 133
M | | 122 | 112 M | 122 | | 122
M | 133 M | | 123 M | | 134 Mos | |
DS2 | 3584 | | | 223 | | 112 | 123
M | 222 | | | | | | | 124
M | |
PGFa | 3916 | | | | | | | | | | | | | | 15 | |
PGMo | 3915 | | | | | | | | | | | | | | 16 | |
MoSib | 3917 | | | | | | | | | | | | | | 26 | |
RDS-15 |
GFa | 1639 | 11 | 11 | | 12 | | 22 | 33 | 11 | | | | | | 12 | |
GMo | 1640 | 11 | 12 | | 12 | | 12 | 12 | 12 | | | | | | 33 | |
DS1 | 1641 | 111 | 112
nr | | 122 | | 122 nr | 123 M nr | 112
nr | | | | 234 nr | | 133 M | 123
nr |
DS2 | 1642 | 111 | 112
nr | | 122 | | 122 nr | 123 M nr | 112
nr | | | | 234 nr | | 133 M | 123
nr |
Fa | 1641 | | | | 11 | | 12 | [23] | [?1] | | | | 23 | | 13 | |
Mo | 1644 | 11 | 11 | | 11 | | 33 | 14 | 11 | | | | 15 | | 45 | 12 |
DS3 | 1645 | 111 | 111 | | 111 | | 113
P r | 122 P r | 111 | | | | 335 P
r | | 334 P r | 111 |
RDS-16 |
[GFa] | | | | | | | | | | | | | [1] | | | [23] |
GMo | 1646 | 11 | 11 | | 11 | | 23 | | 12 | | | | 23 | | 23 | 11 |
DS1 | 1647 | 111 | 111 | | 111 | | 223 | | 122 | | | | 123
nr | | 123 nr | 123 P nr |
Fa | 1648 | 11 | 11 | | 11 | | 13 | | 12 | | | | 12 | | 13 | 23 |
Mo | 1649 | 11 | 11 | | 12 | | 13 | | 12 | | | | [34] | | 45 | |
DS2 | 1650 | 111 | 111 | | 112
nr | | 333
r | | 112 | | | | 134 M
nr | | 145 nr | 233 |
NS1 | 1651 | 11 | 11 | | 11 | | 13 | | 12 | | | | 13 | | 14 | 33 |
NS2 | 1652 | 11 | 11 | | 11 | | 13 | | 12 | | | | 13 | | 14 | 33 |
RDS-17 |
[GFa] | | [2] | [12] | | | | [3] | | | | | [2] | [1] | | [14] | [1] |
GMo | 1662 | 12 | 11 | | | | 12 | | 12 | | | 11 | 23 | | 23 | 12 |
DS1 | 1663 | 122 | 112 | | | | 122 | | 112 | | | 112 | 123
nr | | 123 M nr | 122 |
NS1 | 1664 | 22 | 11 | | | | 23 | | 12 | | | 12 | 13 | | 34 | 11 |
Fa | 1665 | 12 | 11 | | | | 13 | | 12 | | | 12 | 13 | | 13 | 22 |
Mo | 1666 | 12 | 12 | | | | 13 | | 12 | | | 22 | 11 | | 56 | 34 |
DS2 | 1667 | 112 | 112
nr | | | | 113 | | | | | 122 | 113 | | 356
M nr | 234 M nr |
NS2 | 1668 | 22 | 12 | | | | 33 | | 22 | | | 12 | 13 | | 35 | 24 |
RDS-18 |
Fa | 3273 | 12 | | | | | 23 | 12 | | | 12 | 12 | 23 | 22 | 121 | 23 |
Mo | 3272 | 22 | | | | | 23 | 13 | | | 34 | 12 | 11 | 12 | 23 | 13 |
DS1 | 3274 | 122
nr | | | | | 223 | 123
nr | | | 124 P nr | 112 | 123 P
nr | 222 | 123 nr | 223 P r |
NS1 | 3271 | 12 | | | | | 22 | 12 | | | 23 | 12 | 12 | 22 | 13 | 12 |
RDS-19 |
Fa1 | 3275 | 11 | | | | | 22 | | | 13 | 13 | 22 | 14 | 12 | 34 | 12 |
Mo1 | 3276 | 12 | | | | | 22 | | | 24 | 12 | 22 | 34 | 11 | 12 | 11 |
DS1 | 3277 | 112
nr | | | | | 222 | | | 124
M nr | 112 nr | 222 | 344 nr | 112 | 124 M
nr | 111 |
Fa2 | 3278 | 12 | | | | | 22 | | | 44 | 14 | 22 | 34 | 12 | 23 | 12 |
Mo2 | 3279 | 12 | | | | | 12 | | | 11 | 45 | 12 | 12 | 23 | 14 | 23 |
DS2 | 3280 | 122 | | | | | 222 | | | 144
P | 115 P r | 122 | 234 P nr | 123 nr | 123 P
nr | 112 P r |
RDS-20 |
Fa1 | 3799 | | | 12 | | | 12 | 11 | | | 23 | | 22 | | 11 | 22 |
Mo1 | 3800 | | | 13 | | | 11 | 12 | | | 11 | | 13 | | 12 | 13 |
DS1 | 3801 | | | 113
nr | | | 111 | 112 nr | | | 112
M | | 123 M nr | | 112 nr | 123 M nr |
NS1 | 3805 | | | 12 | | | 11 | 12 | | | 13 | | 12 | | 11 | 12 |
Fa2 | 3802 | | | 11 | | | 12 | 11 | | | 23 | | 24 | | 12 | 12 |
Mo2 | 3803 | | | 14 | | | 22 | 11 | | | 14 | | 22 | | 34 | 23 |
DS2 | 3804 | | | 114
nr | | | 222 | 111 | | | 112 M
r | | 222 | | 144 M r | 222 r |
NS2 | 3806 | | | 14 | | | 12 | 11 | | | 13 | | 24 | | 13 | 22 |
RDS-21 |
GMo | 1653 | 12 | 12 | | 12 | | 23 | | 22 | | | 11 | 44 | | 13 | 13 |
Fa1 | 1654 | 11 | 11 | | 22 | | 23 | | 22 | | | 12 | 22 | | 12 | 13 |
Mo1 | 1655 | 12 | 11 | | 12 | | 12 | | 11 | | | 22 | 35 | | 24 | 23 |
DS1 | 1656 | 122 M
r | 111 | | 122 nr | | 123
nr | | 112 M | | | 222 | 235 M
nr | | 224 nr | 123 nr |
NS1 | 1657 | 11 | 12 | | 22 | |
112 | | 12 | | | 22 | 23 | | 24 | 12 |
Fa2 | 1658 | 12 | 12 | | 12 | | 23 | | 22 | | | 11 | 44 | | 23 | 11 |
Mo2 | 1659 | 11 | 11 | | 12 | | 11 | | 12 | | | 11 | 16 | | 15 | 12 |
DS2 | 1660 | 112 | 112 | | 111
r | | 112 M | | 122
nr | | | 111 | 146 M nr | | 125 M
nr | 122 M r |
NS2 | 1661 | 11 | 11 | | 12 | | 13 | | 22 | | | 11 | 46 | | 12 | |
RDS-22 |
Fa1 | 3608 | | | 11 | | 12 | 11 | 23 | | | | | 12 | | 11 | |
Mo1 | 3607 | | | 23 | | 12 | 23 | 13 | | | | | 13 | | 23 | |
DS1 | 3606 | | | 123 M
nr | | 112 | 133 M r | 133
nr | | | | | 123 nr | | 133 M
r | |
Fa2 | 3611 | | | 22 | | 12 | 12 | 12 | | | | | 14 | | 22 | |
Mo2 | 3610 | | | 12 | | 13 | 22 | 34 | | | | | 22 | | 12 | |
DS2 | 3609 | | | 122 | | 112
nr | 122 nr | 124 P
nr | | | | | 124 P
nr | | 122 | |
RDS-23 |
Fa | 3284 | 11 | | | | | | | | 12 | 11 | 22 | | 12 | 14 | 11 |
Mo | 3285 | 12 | | | | | | | | 34 | 12 | 11 | | 13 | 23 | 12 |
DS1 | 3286 | 112
nr | | | | | | | | 234 m
nr | 112 nr | 112 M | | 112 r | 122 M
r | 122 M r |
Haut
References
Abuelo D, Darsel-Bowers G, Busch W, Pueschel S, Pezzullo J (1986) Risk
for trisomy 21 in offspring of individuals who have relatives with trisomy 21.
Am J Hum genet 25:365-369
Alfi O, Chang R, Azen S (1980) Evidence for genetic control of
nondisjunction in man. Am J Hum Genet 32:477-483
Antonarakis SE, Petersen MB, McInnis MG, Adelsberger PA, Schinzel A,
Binkert F, Pangalos G, et al (1992) The meiotic stage of nondisjunction in
trisomy 21: determination using DNA polymorphisms. Am J Hum genet
50:544-550
Antonarakis SE, and the Down syndrome collaborative group (1991)
Parental origin of the extra chromosome in trisomy 21 using DNA polymorphism
analysis. N Engl J Med 324:872-876
Burmeister M, Cox DR, Myers RM (1990) Dinucleotide repeat polymorphism
located at D21 S120. Nucleic Acids Res 18:4969
Daniel A, Stewart L, Saville T, Brookwell R, Paull H, Purvis-Smith S,
Lang-Po-Tang PR (1982) Prenatal diagnosis in 3000 women far chromosome,
X-linked and metabolic disorders. Am J Med Genet 11:61-75
Devoto M, Prosperi L., Dagna-Bricarelli F, Coviello DA, Groci G,
Zelante L, Ferranti G, et al (1985) Frequency of consanguineous marriages among
parents and grandparants of Down syndrome patients. Hum Genet 70:256-258
Dutrillaux B, Lejeune J (1971) Sur une nouvelle technique d'analyse du
caryotype humain. C R Acad Sci 273:2638-2640
Epstein CJ (1989) Down syndrome (trisomy 21). In: Scriver CR, Beaudet
AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, 6th ed.
McGraw-Hill, New York, pp 291-326
Eunpu DL, McDonald DM, Zackai EH (1986) Trisomy 21: rate in second
degree relatives. Am J Med Genet 25:361-363
Giraud F, Mattei JF (1975) Aspects epidemiologues de la trisomy 21. J
Genet Hum 23:1-30
Harris DJ, Begleiter ML, Chamberlin J, Haukins L, Magenis RE (1982)
Parental trisomy 21 mosaicism. Am J Hum Genet 34:125-133
Jabs EW, Warren AC, Taylor EW, Colyer CR, Meyers DA, Antonarakis SE
(1991) Alphoid DNA polymorphisms for chromosome 21 can be distinguished from
those on chromosome 13 using probes homologous to both. Genomics 9:141-146
Jackson-Cook CK, Flannery DB, Corey LA, Nance WE, Brown JA (1985)
Nuclear organizer region variants as a risk factor for Down syndrome. Am J Hum
Genet 37:1049-1061
Lewis JG, Weber JL, Petersen MB, Slaugenhaupt SA, Kwitek A, May PE,
Warren AC, et al (1990) Linkage mapping of the highly informative DNA marker
D21S156 to human chromosome 21 using a polymorphic GT dinucleotide repeat.
Genomics 8:400-402
McInnis MG, Lutfalla G, Slaugenhaupt SA, Petersen MB, Uze G,
Chakravarti A, Antonarakis SE (1991) Linkage mapping of highly informative
polymorphisms of the human interferon alpha receptor gene on chromosome 21.
Genomics 11:573-576
Mikkelsen M, Stene J (1979) Previous child with Down syndrome and
other chromosome aberration: group report. In: Murken JD, Stengel-Rutkowski S,
Schwinger E (eds) Prenatal diagnosis: proceedings of the 3rd European
Conference on Prenatal Diagnosis of Genetic Disorders. Enke, Stuttgart, pp
22-29
Nielsen KG, Poulsen H, Mikkelsen M, Steuber E (1988) Multiple
recurrence of trisomy 21 Down syndrome. Hum Genet 78:103-105
Pangalos C, Serre JL, Ghica M, Abazis D, Sinet PM, Rethore MO, Lejeune
J (1988) Molecular analysis of the parental origin of trisomy in two families
with two children having regular trisomy 21. Ann Genet 31:151-154
Petersen MB, Economou EP, Slaugenhaupt SA, Chakravarti A, Antonarakis
SE (1990) Linkage analysis of the human HMG14 gene on chromosome 21 using a GT
dinucleotide repeat as polymorphic marker. Genomics 7:136-138
Petersen MB, Schinzel AA, Binkert F, Tranebjaerg L, Mikkelsen M,
Collins FA, Economou EP, et al (1991a) Use of short sequence repeat DNA
polymorphisms, after PCR amplification to detect the parental origin of the
additional chromosome 21 in Down syndrome. Am J Hum Genet 48:65-71
Petersen MB, Slaugenhaupt SA, Lewis JG, Warren AC, Chakravarti A,
Antonarakis SE (1991b) A genetic linkage map of 27 markers on human chromosome
21. Genomics 9:407-419
Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, Arnheim
N (1985) Enzymatic amplification of betaglobin genomic sequences and
restriction site analysis for diagnosis of sickle cell anemia. Science
230:1350-1354
Schwartz S, Roulston D, Cohen MM (1989) dNORs and meiotic
nondisjunction. Am J Hum Genet 44:627-430
Seabright M (1971) A rapid banding technique for human chromosomes.
Lancet 2:971-972
Sherman SL, Takeasu N, Freeman SB, Grantham M, Phillips C, Blackston
RD, Jacobs PA, et al (1991) Trisomy 21: association between reduced
recombination and nondisjunction. Am J Hum Genet 49:608-620
Southern EM (1975) Detection of specific sequences among DNA fragments
separated by gel electrophoresis. J Mol Biol 98:503-517
Tamaren J, Spuhler K, Sujansky E (1983) Risk of Down syndrome among
second and third degree relatives of a proband with trisomy 21. Am J Med Genet
15:393-404
Uchida IA, Freeman VCP (1985) Trisomy 21 Down syndrome: parental
mosaicism. Hum Genet 70:246-248
Van Camp G, Backhovens H, Cruts M, Wehnert A, Van Hul W, Stinissen P,
Van Broeckhoven C (1991) Identification of chromosome 21 DNA polymorphisms for
genetic studies in Alzheimer disease and Down syndrome. Hum Genet 87:49-653
Warren AC, Chakravarti A, Wang C, Slaugenhaupt SA, Halloran SL,
Watkins PC, Metaxotou C, et al (1987) Evidence for reduced recombination an the
nondisjoined chromosome 21 in Down syndrome. Science 237:652-654
Warren AC, Petersen MB, van Hul W, McInnis M.G, van Broeckhoven C, Cox
TK, Chakravarti A, Antonarakis SE (1992) D21S215 is a (GT)n polymorphic marker
close to the centromeric alphoid sequences on chromosome 21. Genomics
13:1365-1367
Warren AC, Slaugenhaupt SA, Lewis JG, Chakravarti A, Antonarakis SE
(1989) A genetic linkage map of 17 markers on human chromosome 21. Genomics
4:579-591
Yokohama S, Reich T, Morgan K (1981) Inbreeding and the genetic
control of nondisjunction. Hum Genet 59:125-128
|