Deleterious effects of the reciprocal translocations are widely known,
but their relation to the topologic changes of the chromatids needs further
investigation. Thus, it seemed useful to analyze carefully the 95 reciprocal
translocations observed among the 9183 patients studied since banding
techniques became available in our laboratory.
Our intention was to seek a correlation among the localization of
break points, the chromosomes or segments there of involved in the
rearrangements, and the types of segregation observed in the families
Materials and Methods
1. Samples Studied
All our structural rearrangements were ascertained through
pathologic circumstances that provoked a karyotype study. Of 9183 patients
examined by chromosome banding, 3211 were children of 15 years or less with
malformations and/or mental retardation.
An unbalanced chromosomal anomaly was detected in 870 of these
(trisomies 21: 762; trisomies 18: 29; trisomies 13: 23; and 56 other
miscellaneous aberrations, including unbalanced translocation carriers).
In the 2341 other children, clinical examination did not suggest any
known chromosomal syndrome. The remaining 5972 patients were adults seeking
consultation essentially for reproductive difficulties (spontaneous abortion,
infertility, malformed children).
It is noteworthy that the proportion of adults referred to us has
increased progressively in recent years and now constitutes the majority of our
2. Cytogenetic Studies
Lymphocyte cultures were carried out according to the usual
micromethod. All of our patients were analyzed with the use of R banding (RHG).
Among the translocation carriers, 37 were also studied by Q banding (QFQ).
Finally, many of the translocations were observed by T banding (THA), C banding
(CBG), or after treatment for 7 h with BrdU followed by staining with acridine
3. Ascertainment and Classification of the
Our 95 translocations (see attached list) were separated into two
groups and eight classes according to their mode of ascertainment and the type
of malsegregation observed:
Balanced parental translocations ascertained through children with
unbalanced karyotype as follows:
46 chromosomes (2:2 segregation): 30 cases;
47 chromosomes (3:1 segregation): 18 cases;
45 chromosomes (1:3 segregation): 5 cases.
Balanced translocations found:
in couples having had several spontaneous abortions (S.A.): 12
in children with malformations and/or mental retardation (Bal.):
in children with free trisomy 21 or in one of their parents
(possible interchromosomal effect: I.C.E.): 5 cases;
in sterile patients (Ster.): 7 cases;
miscellaneous (Misc.): 3 cases.
4. Definition of the knits of Chromosome Length Used for
Considering that the haploid human karyotype in metaphase consists
of approximately 300 bands, we have used 1/300 of the karyotype 24,XY as a
basic unit (U) of length in order to quantify the length of the segments
involved in the rearrangements. The relative length of the different
chromosomal arms was measured on the schema of the Descriptive Plates of Human
Chromosomes (Prieur et al., 1973). Thus, for example, the short arm of
chromosome 1 measures 12 U and the long arm, 14 U.
Having voluntarily excluded translocations involving sex chromosomes
(whose combined length represents 20 U), we base our calculations on the 280 U
of length of the autosomes.
1. Localization of Break Points
The break points of each translocation were determined by two
independent groups of observers and the results compared. The localizations
retained for our 190 points are represented in Figure 1.
1. Localization of break points
a) Localization of Break Paints in Relation to Bands
We have retained, for this part of the analysis, only the 37
translocations that were studied both by R bands and Q bands. The distribution
of the 74 break points at the level of R bands, Q bands and their interfaces,
and tips of the chromosomes is indicated in Table I. It is clear from this
table that there is an obvious excess at the level of the interfaces.
b) Distribution of Breakpoints According to the
In Figure 1, we have noted, next to each chromosome arm, the
number of break points expected in function of its length. Certain chromosome
arms present an obvious deficiency or excess of break points. In order to
consider only those translocations whose malsegregation leads to an unbalanced
state known a priori to be compatible with life, and in order to normalize the
length of the segments involved, we have taken into account only those break
points situated on terminal segments 3.5-U-long carried on chromosome arms of
at least that length (a length of 3.5 U corresponds to the long arm of
chromosome 21 and represents 1/80 of the haploid karyotype); 71 break points
situated on non terminal segments are thus excluded. In addition, this method
of weighting has obliged us to exclude a certain number of chromosome arms
whose length is clearly less than 3.5 U (smallest arms: Sm.a.). Thus, we have
not considered the 15 break points situated on the short arms of the
acrocentrics, and on the 17p, 18p, 19p, and 20p (total length of these arms is
18.5 U). There remain 104 break points situated on the 122.5 U of the 35
terminal segments (each of which is 3.5 U long). The distribution of these 104
terminal break points is given in Table 2. Here again, we have subdivided the
sampling into two classes according to whether the break points sit on large
arms L (greater than 6 U) or on small arms S (less than, or equal to, 6 U).
A total of 175 break points was observed on chromosome arms longer
than 3.5 U (104 on terminal segments plus 71 on non terminal segments, as noted
above). If these had been evenly distributed throughout the length of the
chromatids, we would have expected 81.6 terminal break points instead of the
104 observed (?2 = 11.52 for v = 1).
There is, therefore, a significant excess of terminal break
points, the mean observed being 2.97 break points per terminal segment. In
order to determine if certain of these segments present an excess of break
points, the probability of finding k break points on a given terminal segment
can be calculated by applying Poisson's law: P(k) =
This law shows that the excess becomes significant in the case of
seven o more break points (probability of observing at least seven points: P=
0.032). In our sampling, this excess exists for the 4p, 9p, 10q, 21q, and 22q.
The mode of ascertainment of the translocations involving these chromosome arms
is indicated in Table 3.
We could not detect a possible deficiency of break points on
certain arms because the absence of break points on a terminal segment is at
the limit of statistical significance (P = 0.051). For this reason, we have
grouped our data with that obtained by two other authors (Jacobs et al., 1974b;
Turleau et al., 1975) which permits us to add 57 terminal break points to our
sampling (Table 2). The average expected number of break points per terminal
segment is thus 4.6. The absence of break points on a terminal segment has a
probability of only 0.01 and becomes significant for the 1p, 2p and 6q. The
excess of break points becomes significant with nine or more (probability of
observing at least nine points: P=0.045) and still exists for the 4p, 9p, 10q,
21q, and 22q, and only for these.
Table I. - Localization of 74 break points in the 37
translocations studied both in R and Q banding
|R: R bands; Q: Q bands; I: interfaces; Tips:
tips of the chromatids; Group I: unbalanced translocation carriers; S.A.:
spontaneous abortion; Bal.: malformed children carriers of a balanced
translocation; I.C.E.: possible interchromosomal effect; Ster.: sterility;
Table 2. - Distribution of break points on terminal
segments 3.5 U long
|Large Arms, L (> 6 U)
Table 3. - Ascertainment of translocations involving arms
with an excess of break points
|Group I: unbalanced-translocation carriers;
S.A.: spontaneous abortion; Bal.: malformed children carriers of a balanced
translocation; Ster.: sterility; Misc.: miscellaneous
|Small Arms, S (= 6 U)
|I.P.: present study of lnstitut de
Progenese; J.: study of Jacobs et al., 1974 b; T.: study of Turleau et aL,
1975). * Significant deficiency ** Significant excess
c) Distribution of Break Points Along the Chromatids.
We looked for a possible accumulation of break points in the
centromeric or telomeric regions of the chromosome arms. In view of this, we
have arbitrarily decided that a break point is telomeric or centromeric when it
is situated at a distance less than, or equal to, one length unit from the
telomere or the centromere. The arms previously excluded (short arms of the
acrocentrics, and 17p, 18p, 19p, and 20p) form a separate category (smallest
arms: Sm.a.) for which it is impossible to define the centromeric (C), median
(M), and telomeric (T) regions.
Table 4 represents the observed distribution (o) of break points
according to this classification (T, C, M, and Sm.a.) and takes into account
the mode of ascertainment of the translocation. It also indicates the
theoretical distribution (t) in function of length for each of the
Among the translocations taken as a whole, we do indeed find the
excess of telomeric and centromeric break points previously noted (Lejeune et
al., 1972; Jacobs et al., 1974b). Furthermore, close analysis of our data shows
that most of this excess falls into group I.
Let us recall that:
Group I is composed of translocations ascertained though live-born
'unbalanced' children (segregation 2:2, 3:1, and 1:3). This group farms a
statistically homogeneous ensemble; after having grouped together the 3:1 and
1:3 segregation classes of translocations (for reasons of insufficient
individual samples), the test for homogeneity gives:
?2 (2:2)/(3:1 + 1:3) = 4,98, for v = 3.
Group II is composed of translocations ascertained through a
balanced carrier (S.A., Bal., Ster., I.C.E., Misc.) and also forms a
statistically homogeneous ensemble. Grouping together translocations Ster.,
I.C.E., and Mist. and classes M and Sm.a., the test for homogeneity gives:
?2 (S.A.)/(Bal.)/(Ster. + I.C.E. + Misc.) =
3.32, for v=4.
The distributions observed in these two groups are significantly
different (test for homogeneity: ?2 = 8.06 for v = 3).
The first group of translocations differs from the theoretical
distribution (?2 = 42.5 for v = 3) as a consequence of:
- an excess of telomeric break points in the 3:1 and 1:3 classes
(?2 = 7.74 for V =1);
- an excess of centromeric break points in the 3:1 and 1:3 classes
(?2 = 5.48 for v = 1);
- a large excess of telomeric break points in the 2:2 class
(?2 = 23.8 for v = 1).
The second group of translocations does not differ from the
theoretical distribution (?2 = 5.45 for v = 3).
The slight excess of telomeric break points is not significant
(?2 = 3.29 for v = 1).
Table 4. - Distribution of break points along the
|N||Telomeric region||Centromeric region||Median region||Smallest
arms||?2 v = 3
I||2/2||60||20||7.50||5||7.50||27||41.00||8||4.00|| ?2 homogeneity: 4.98 v=3
II||S.A.||24||5||3.00||3||3.00||15||16.40||1||1.60|| ?2 homogeneity: 3.318 v=4 (a)
|Total group I +
|(a) see text. o: observed; t:
2. Analysis of the Types of Translocations
a) Distribution of the Classes of Translocations
Described Above in Function of Break Points.
We have just localized the break points in telomeric (T), median
(M), and centromeric (C) regions, or on the smallest chromosome arms (Sm.a.).
This permits us to define a translocation by localization of its two break
points. Thus, one may observe TT, TM, or TC translocations, etc. The
distribution of our translocations according to this classification is
indicated in Table 5. Several casses of translocations contain a sampling
sufficiently large to permit statistical analysis. Thus we observe:
2:2 class: clear-cut excess of forms TM in relation to the other
classes of transiocation (?2 = 10.36 for v = 1, P <
3:1 class: excess of forms CM (?2 = 5.69 for v =
1, P < 0.0125) and no excess of forms TM;
S.A. class: excess of MM (?2 = 4.45 for v = 1, P
Bal. class: no significant excess of any of the forms.
The other classes of translocations contain a sampling too small
to justify statistically study.
b) Distribution of the Classes of Translocation in
Function of the Length of the Arms evolved.
Let us recall that the definition of large arm (L) is any arm
measuring more than 6 U, and that an arm is considered small (S) when it
measures 6 U at the most. (6 U corresponds to the short arm of chromosome 6.)
For purposes of this analysis, the short arms of the acrocentrics, and 17p,
18p, 19p, and 20p, have yen included in the category of small arms (S).
The total length of the small arms of the autosomes is 93 U; that
of the large arms is 187 U (i.e., a ratio of 1/3 S to 2/3 L). Our
translocations may thus be classified as SS, LS, SL, and LL where the
theoretical distribution is 1/9, 2/9, 2/9, and 4/9, respectively. Table 6 gives
the distribution of our 95 translocations according to this classification. The
two categories SL and LS are distinguished by placing first the chromosome arm
(L or S) that is lengthened by the rearrangement.
The distribution observed in the total sampling differs
significantly from the theoretical distribution (?2 = 14.05
for v=3). This discrepancy is the consequence of an excess of forms SS and SL
and a deficiency of forms LL and LS. However, the abnormal distribution is not
found uniformly among the classes of translocations denoted, not being observed
in the group of translocations ascertained in a balanced carrier (group II),
but observed in the group of translocations ascertained through an unbalanced
carrier (group I) (?2 = 27 for v = 3, P < 0.0005). In this
group I, the excess of small arms involved (2 SS + SL + LS) is marked
(?2 = 21.8 for v = 1).
We wanted to know if this excess of small arms (S) would persist
if we were to exclude translocations involving any of the smallest arms (Sm.a.:
short arms of the acrocentrics, and 17p, 18p, 19p, and 20p). In fact, even
after this correction, the excess of small arms (S) in translocation group I is
still very significant (?2 = 11.12 for v = 1, P <
c) Analysis in Function of the Possible Induced
For each class of translocation, we can calculate in length units
the possible unbalanced states induced at the time of malsegregation. The
results of this analysis are indicated in Table 7 and 8.
Translocations of the 2:2 segregation class and of the
telomeric-median category (TM) generally lead to an unbalanced karyotype,
consisting of trisomy of a medium-sized segment, with a small terminal
monosomy. However, several translocations in the same category have led, on the
contrary, to a small terminal trisomy and a monosomy for a medium-sized
segment. In these three particular cases, the monosomic segments are: the 4p
(two instances, IP No. 12563 and If` No.14619) and the 5p (one instance,
Laurent et al., 1974).
In the class of the 3:1 segregation translocations, four have
produced an imbalance longer than 6 U. These four observations were ascertained
through a child carrying a trisomy of the short arm of chromosome 9.
Table 6. - Distribution of the classes of translocation in
function of the length of the arms involved
|SS||LS||SL||LL||Total ||?2 v = 3
|a 10 translocations involving smallest arms;
b 2 translocations involving smallest arms. (S: small arms < 7 U; L: large
arms > 6 U; o: observed; t: theoretical)
Table 7. - Observed mean imbalance. Group I
|Classes of segregation||Mean trisomy||Mean
monosomy||Total mean imbalance
|2:2||TM : 3.85 ± 1.83 n =
17||TM : 0.47 n = 17||4.03 ± 1.63 n = 30
|non-TM: 2.63 ± 1.42 n = 13||non-TM: 1.01 n =
|3:1||4.22 ± 2.43 n = 18||0||4.22 ±
2.43 n = 18
|1:3||0||1.68 ± 0.90 n = 5||1.68 ±
0.90 n = 5
Table 8. Possible mean imbalance. Group II
(balanced-translocation carriers) in case of 2:2 segregation
|Classes of segregation||Possible mean
|S.A.||7.47 ± 3.39
|Bal.||8.14 ± 3.60
|Ster.||8.46 ± 4.60
In this section we intend to discuss the different steps in our
analysis, but will begin with a discussion of the frequency of balanced
translocations observed in malformed children, and in trisomics 21 and their
Balanced Translocations Found in Children Kith
Malformations and/or Mental Retardation
In the 2341 children not suspected of having chromosomal
abnormalities whose karyotypes we recently studied, we end 13 reciprocal
balanced translocations (see attached list, numbers greater than 10,000). Four
translocations figuring in this list represent reexaminations and are not taken
Routine study of the karyotypes of newborn children carried out in
various laboratories (Lubs and Ruddle, 1970; Walzer and Gerald, 1972; Jacobs et
al., 1974a; Nielsen and Sillesen, 1975; Hamerton et al., 1975) shows that the
frequency of this type of rearrangement in the general population is
approximately 1 in 1200 births.
The probability of observing, as in our sampling, 13 balanced
translocations among 2341 children is furnished by the binomial
P = 1.5 x 10-7.
Our sampling thus differs significantly from the general
To explain this difference, we might suppose that the translocations
observed de novo in a proband are slightly unbalanced, the loss or alteration
of genetic material remaining undetectable by current banding techniques. There
remain seven familial translocations for which no cytologic technique has
permitted us to demonstrate a difference between the translocation carried by
the relatives with normal phenotype and that observed in the proband. We might
therefore suppose that these seven translocations are not unbalanced. The
binomial law, applied only to these seven translocations, furnished a
P = 4 x 10-3.
In function of these results, it seems reasonable to consider the
possibility in these cases of a relationship of causality between the
translocation and the observed syndrome, as several authors have proposed
(Jacobs, 1974; Tharapel et al., 1977; Viguié, 1977; Funderburk et al.,
It should be noted that the great majority of these balanced
translocations are accompanied by a marked modification of the centromere index
of the involved chromosomes. These topologic changes, while modifying the
respective positions of different segments of the genome, might also disturb
its replication or regulation (position effect).
This explanation seems to have received cytologic confirmation for X
chromosome translocations which we have voluntarily eliminated from our study
(Dutrillaux, 1974; Dutrillaux et al., 1974a).
The phenotypic discordance observed between a parent carrying the
translocation and the malformed child is not easily understood. One hypothesis
could be that the phenotype depends upon the alleles carried by the
translocated chromosomes and by their normal counterparts. Allelic differences
between parent and child are expected both by cross-over and normal
It is interesting to note that the diseases observed in these
children are often genie disorders considered dominant with variable
expression. One of the translocations involving chromosome 2 was ascertained
through two children affected by Crouton's syndrome (craniofacial dysostosis).
We have observed the same syndrome in a child with a pericentric inversion of
chromosome 2. In addition, a translocation involving chromosome 15 was found in
a child who had Prader-Willi's syndrome. Besides this, two observations of
translocations involving chromosome 15 and associated with the same disorder
have already been published (Hawkey and Smithies, 1976; Emberger et al.,
Although outside the framework of this study, let us note that
reciprocal translocations do not seem to be the only rearrangements capable of
modifying the phenotype. In the same sampling of 2341 phenotypically abnormal
children, we observed five translocations t(13q14q) and two pericentric
inversions. In the general population, the estimated incidence of these
rearrangements is, respectively, 1 in 1200 and 1 in 10,000. The probability of
observing in our sampling five translocations t(13q14q) is thus 4.8 x
10-2 and that of observing two pericentric inversions is 2.3 x
Balanced Translocations Found in Children With Trisomy 21
and Their Parents
In the 762 children with trisomy 21, we observe three inherited
balanced reciprocal translocations affecting other chromosomes than No. 21. The
two other translocations observed in our general sample represent reexamination
and are therefore eliminated from this analysis. The probability of observing
these three translocations in a population of 762 children is:
P = 2.6 x 10-2 (binomial distribution).
This excess of reciprocal translocations is in harmony with the
hypothesis of the interchromosomal effect (I.C.E.) postulated by Lejeune
(1963). These observations would lead one to think that balanced structural
rearrangements may influence the segregation of other elements, and the
chromosome 21 in particular.
This interchromosomal effect does not seem to be limited to
reciprocal translocations since, in the parents of these 792 children with
trisomy 21, we observed also two pericentric inversions (excluding those
affecting chromosome 9). Among the chromosomes involved in the five
translocations and the two pericentric inversions we observed, it is noteworthy
that the majority are carriers of DNA coding for ribosomal RNA (Henderson et
al., 1972; Johnson et al., 1974; Pardo et al., 1975) or of segments with very
late replication, seemingly corresponding to heterochromatin
Localization of Break Points in Relation to Bands and
We observed an excess of break points at the level of the interfaces
between chromosome bands. This observation may be compared with the results
obtained by analysis of the exchange of chromatids (Dutrillaux et al., 1974b),
of break points in Fanconi's anemia (Dutrillaux et al., 1977), and of
radiation-induced chromosomal rearrangements (Buckton, 1976; Dubos et al.,
1978) where the same excess has been noted.
This reinforces the idea that there may be 'fragile' sites at the
level of the interfaces whose particular structure favors the occurrence of
chromosomal rearrangements (Dutrillaux,1977).
Chromosome Arms Showing an Excess of Break
With the notable exception of chromosome 22, all of the chromosomes
tending to show an excess of break points are implicated in the etiologies of
well known and relatively frequent chromosomal disorders (4p-, tri4p, 9p-,
tri9p, tri 10q, tri21).
Two hypotheses may account for this observation:
These chromosome arms manifest a particular fragility and the excess
of break points observed in our translocations and in the 'classical' syndromes
is merely a reflection of this fragility.
These chromosome arms have no particular fragility, but monosomies
and trisomies of these segments are relatively well tolerated. The
translocations involving these chromosome arms are thus more readily
ascertained, especially in children carrying unbalanced karyotypes.
This second hypothesis seems the more probable. However, it does not
permit us to explain the excess of break points observed an chromosome 22, an
excess all the more surprising because pathology of this chromosome is
exceptionally rare and limited to small segments. In the translocations of
chromosome 22 that we present, when an imbalance was observed in a child, the
contribution of chromosome 22 was always very slight, mostly limited to the
juxtacentromeric or the telomeric regions of the long arm.
It is interesting to note that we have three identical
translocations t(8;22) and two identical translocations t(11;22). In addition,
this last translocation is found very frequently at the time of ascertainment
through a child with trisomy 11q.
These remarks lead us to believe that chromosome 22 possesses a
preferential subcentromeric break point (which is also found in the formation
of the Philadelphia chromosome) and that it manifests, in addition, a certain
'affinity for translocation' with specific chromosomes such as 8, 9, and
Chromosome Arms Manifesting a Deficiency of Break
In our sampling, three chromosome arms, the 1p, 2p, and 6q, manifest
very few break points. Trisomies and monosomies involving these segments are
extremely rare in human pathology but have already been observed in the
products of early spontaneous abortions.
One might think that an aneusomy involving these chromosome segments
permits only brief intrauterine survival. The absence of break points observed
in these segments would therefore be the consequence of a bias of
Localization of Break Points on the
When translocations are ascertained through a balanced carrier
(group II), the break points distribute themselves regularly along the
different chromosome segments. There is, nevertheless, a slight excess of
telomeric break points that is not felt to be significant.
On the other hand, the excess of telomeric break points among the
translocations ascertained through a child with an unbalanced karyotype (group
I) is significant. This is particularly clear for the class of 2:2
translocations and corresponds, in unbalanced probands, to monosomy (and far
more rarely to trisomy) for very small segments.
This situation is probably directly related to the eventual survival
of subjects with unbalanced karyotypes. The excess of telomeric break points
observed here may also be explained by a bias of ascertainment.
In the 3: and 1:3 segregation classes of translocations, we note in
addition an excess of centromeric break points. This type of translocation
always corresponds to the formation of a small element that malsegregates at
the time of parental meiosis. The majority of these translocations involves an
acrocentric chromosome that furnishes the short arm and the centromeric region
of the small element.
Analysis of the Malsegregations Observed in Group I
(translocations ascertained through a proband with unbalanced
The translocations with 2:2 segregation of this group are
ascertained through unbalanced carriers. This presupposes that a segregation of
the adjacent type occurs at the time of parental meiosis.
The type of meiotic segregation of translocation probably depends on
the number of crossing-over that can occur between the centromere and the point
of exchange of the translocation (McClintock, 194; Burnham, 1956; Hamerton,
If there is no crossing-over on the segment, an adjacent segregation
is to be expected and the gametes will be unbalanced.
If there is a single crossing-over, half of the gametes could be
If there is a crossing-over on each of the chromatids, the
segregation will generally be of the alternate type and the gametes will be
If the segment situated between the centromere and the point of
exchange of the translocation is small, one can expect an excess of unbalanced
gametes. For large segments, the number of crossing-over becomes random and
this excess of unbalanced gametes should not, theoretically, be noted.
Perhaps these theoretical remarks furnish an explanation for the
clear excess of chromosomal small arms involved in this class of 2:2
We have seen that the 3:1 segregation translocations correspond to
the malsegregation of a small structurally rearranged element at the time of
In the 18 cases that we present, this malsegregation always occurred
during the first meiotic division so that the proband received, along with the
small supernumerary element, 46 other normal chromosomes. It is therefore
indispensable to study the parent's karyotypes to determine the precise nature
of this small element.
One might conclude that the malsegregation of the small element is
the consequence of a particular topological configuration imposed by the size
of this element at the time of the pairing of the chromosomes in the first
It is interesting to note that, of our 18 cases, 17 are the
consequence of maternal translocation. This preponderance of maternal origin
has already been noted for trisomy 9p, where the 16 cases collected by Lurie et
al. (1976) corresponding to a malsegregation of the 3:1 type, all result from
maternal translocation. The same is true for the seven published cases of
trisomy 11q by translocation t(11;22) (Aurias et al., 1975; Laurent et al.,
1975; Giraud et al., 1975; Ayraud et al., 1976; Noel et al., 1976; Kessel and
This maternal preponderance is not found among translocations having
undergone a segregation of the 2:2 type. 0f the 28 cases that we report, 12 are
of paternal origin and 16 of maternal origin.
We have not found any obvious bias of ascertainment that would allow
us to explain the excess of maternal translocations in the 3:1 segregations.
There is no increase in the mean maternal age.
Perhaps explicable in terms of diminished fertility or even
sterility among men carrying such translocations (Dutrillaux,1973a; Laurent et
al., 1977), this excess probably reflects a fundamental difference between the
male and female meiosis, a difference whose precise nature remains unknown.
Average :Length of Possible Induced Imbalance in Cases of
Our results permit us to quantify to a certain degree the importance
of the observed chromosomal imbalances.
Thus, 1:3 segregation (leading to monosomies) manifest an average
imbalance of 1.68 U, while 3:1 segregations (leading to trisomies) yield an
average imbalance of 4.22 U. This could indicate that the trisomies are
relatively better tolerated than the monosomies. This feeling is strengthened
by the analysis of 2:2 segregations, where the segment in triplicate is
generally longer than the monosomic segment, and where the length of the
trisomic segment is reciprocally proportional to that of the monosomic one (TM
translocations: 3.85 U long trisomy for a 0.47 U long monosomy; non TM
translocations: 2.63 U trisomy for 1 U Long monosomy).
The translocations ascertained through spontaneous abortions (S.A.)
present a total imbalance of 7.5 U, which is less marked than that observed in
cases of sterility (8.46 U) or balanced translocations (8.14 U).
These results are on the whole satisfying and permit us to relate
the severity of the resulting disorders to the length of the involved
However, a certain number of translocations disobey this rule
appreciably. Other parameters beside length must therefore influence the
severity of chromosome disorders. Among these, two seem to play an important
the genic content of the involved segments;
the replication time of these segments.
It seems quite possible to us that trisomy or monosomy of early
replicating R bands are less well tolerated than imbalances of late replicating
R bands or Q bands (whose replication is always late) (Dutrillaux et al.,
Aurias, A., Turc, C., Michiels, Y., Sinet, P. M., Graveleau, D.,
Lejeune, J.: Deux cas de trisomie 11q(q231? qter) par translocation
t(11;22)(q23.1;q11.1) dans deux familles différentes. Ann. Génét. (Paris)
18, 185-188 (1975)
Ayraud, N., Galiana, A., Llyod, M., Deswarte, M.: Trisomie
11q(q231?qter) par translocation maternelle t(1 1;22)(q23.1;q11.1). Une
nouvelle observation. Ann. Génét. (Paris) 19, 65-68 (1976)
Buckton, K. E.: Identification with G and R banding of the position of
breakage points induced in human chromosomes by `in vitro' X irradiation. Int.
J. Radiat. Biol. 29, 475-488 (1976)
Burnham, C. R.: Chromosome interchanges in plants. Bot. Rev. 22,
Carpentier, S., Rethoré, M. O., Lejeune, J.: Trisomie partielle 7q
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Dutrillaux, B.: Chromosomal aspects of human male sterility. In: Nobel
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Dutrillaux, B., Jonasson, J., Kerstin, L., Lejeune, J., Lindsten, J.,
Petersen, G. B., Saldana- P.: An unbalanced 4q/21 q translocation identified by
the R but not by the G and Q chromosome banding techniques. Ann. Genet. (Paris)
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Dutrillaux, B.: Study of human X chromosomes with the 5-BrdU-acridine
orange technique. Application to X chromosome pathology. In: Chromosome today,
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Dutrillaux, B., Laurent, C., Gilgenkrantz, S., Frederic, J.,
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Etude après traitement par le, BUDS et coloration par l'acridine orange. Helv.
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Dutrillaux, B., Fosse, A.-M., Prieur, M., Lejeune, J.: Analyse des
échanges de chromatides dans les cellules somatiques humaines. Chromosome 48,
Dutrillaux, B., Laurent, C., Farabosco, A., Noel, B.. Suerinc, E.,
Biemont, M. C., Cotton, JB.: La trisomie 4q partielle. A propos de trois
observations. Ann. Genet. (Paris) 18, 21--27 (1975)
Dutrillaux, B.: Qbtention simultanée de plusieurs marquages
chromosomiques sur les même preparations, après traitement par le BrdU.
Humangenetik 30, 297-306 (1975)
Dutrillaux, B., Couturier, J., Richer, C. L., Viegas-Pequignot, E.:
Sequence of DNA replication in 227 R and Q bands of human chromosomes using a
BrdU treatment. Chromosome 58, 51-61 (1976)
Dutrillaux, B., Couturier, J., Viegas-Pequignot, E., Schaison, G.:
Localisation of chromatid breaks in Fanconi's anemia using three consecutive
stains. Hum. Genet. 37, 65-71 (1977)
Dutrillaux, B:: Models théorique de I'induction des remaniements
structuraux des chromosomes. Ann. Génét. (Paris) 20, 221-226 (1977)
Emberger, J. M., Rodiere, M., Astruc, J., Brunei, D.: Syndrome de
Prader-Willi et translocation 15-15. Ann. Génét. (Paris) 20, 297-300
Forabosco, A., Dutrillaux, B., Toni, G., Tamborino, G., Cavazzuti, G.:
Translocation équilibrée t(2;13)(q32;q33) familiale et trisomie 2q partielle.
Ann. Génét. (Paris) 16, 255-258 (1973)
Funderburk, J., Spence, M. A., Sparkes, R. S.: Mental retardation with
'balanced' chromosomal rearrangements. Am. J. Hum. Genet. 29, 136-141
Giovannelli, G., Forabasco, A., Dutrillaux, B.: Translocation
familiale t(4;22)(p11;p12) et trisomie 4p chez deux germains. Ann. Génét.
(Paris) 17, 119-124 (1974)
Giraud, F., Matteï, J. F., Matteï, M. G., Bernard, R.: Trisomie
partielle 11q et translocation familiale 11-22. Humangenetik 28, 343-347
Hamerton, J. L.: Human cytogenetics, Vol. 1, pp. 248-251. New
York-London: Academic Press 1971
Hamerton, J. L., Canning, N., Ray, M., Smith, S.: A cytogenetic survey
of 14,069 newborn infants. I. Incidence of chromosome abnormalities. Clin.
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Hawkey, C., Smithies, A.: The Prader-Willi syndrome with a 15/15
translocation. Case report and review of the literature. J. Med. Genet. 13,
Henderson, A. S., Warburton, D., Atwood, K. C.: Location of ribosomal
DNA in the human chromosome complement. Proc. Natl. Acad. Sci. USA 69,
Jacobs, P. A., Melville, M., Ratcliffe, S.: A cytogenetic survey of
11,680 newborn infants. Ann. Hum. Genet. 37, 359-376 (1974a)
Jacobs, P. A., Buckton, K. E., Cunningham, C., Newton, M.: An analysis
of the break points of structural rearrangements in man. J. Med. Genet. 11,
Jacobs, P. A.: Correlation between euploid structural chromosome
rearrangements and mental subnormality in humans. Nature 249, 164-165
Johnson, L. D., Henderson, A. S., Atwood, K. C.: Location of the genes
for S SRNA in the human chromosome complement. Cytogenet. Cell Genet. 13,
Kessel, E., Pfeiffer, R. A.: 47,XY,+der(11;22)(q23;q12) following
balanced translocation t(11;22) (q23;q12)mat. Humangenetik 37, 111-11b
Laurent, C., Dutrillaux, B., Biemont, M. C., Genoud, J., Bethenod, M.:
Translocation t(14q-; 21q+) chez le père. Trisomie 14 et monosomie 21
partielles chez la fille. Ann. Génét. (Paris) 16, 281-284 (1973)
Laurent, C.: Trisomie 10 partielle par translocation familiale
t(1;10)(q44;q22). Humangenetik 18, 321-327 (1973)
Laurent, C., Biemont, M. C., Robert, J. M., Dutrillaux; B.:
Identification de deux translocations familiales. Ann. Génét. (Paris) 17,
Laurent, C., Biemont, M. C., Bethenod, M., Cret, L., David, M.: Deux
observations de trisomie 11q(q231? qter) avec la même anomalie des
organes génitaux externes. Ann. Génét. (Paris) 18, 179-184 (1975)
Laurent, C., Biemont, M. C., Cognat, M., Dutrillaux, B.: Studies of
the meiotic behavior of a translocation t(10;13)(q25;q11) in a oligospermic
man. Hum. Genet. 39, 123-1126 (1977)
Lejeune, J.: Autosomal disorders. Pediatrics 8, 326-337 (1963)
Lejeune, J., Dutrillaux, B., Rethoré, M. O., Prieur, M., Couturier,
J., Carpentier, S., Raoul, O.: Analysis of 30 cases of translocation by the
controlled heat denaturation. In: Modern aspects of cytogenetics: Constitutive
heterochromatin in man, pp. 191-200. Stuttgart: Schattauer 1972
Lejeune, J., Rethoré, M. O., Dutrillaux, B., Lafourcade, J.,
Cruveiller, J., Drillon, Ph.: Syndrome 4p- par translocation paternelle
t(4;20)(p15;p12). Lyon Med. 233, 271-274 (1975)
Lubs, H. A., Ruddle, F. M.: Chromosomal abnormalities in the human
population: Estimation of rates based on Newhaven newborn study. Science 169,
Lurie, I. W., Lazjuk, G, L, Gurevich, D. B., Usoev, S. S.: Genetics of
the +9p syndrome. Hum. Genet. 32, 23-33 (1976)
McClintock: Preliminary observations of the chromosomes of Neuropora
crassa. Am. J. Bot. 32, 671-678 (1945)
Marcelli, A., Benajam, A., Poirier, J. C., Dausset, J., Rethoré, M.
O., Prieur, M., Lejeune, J.: Etude d'une modification de l'expression du locus
ABO chez un sujet 47,XY,(?18q-)+. Hum. Genet. 22, 233-241(1974)
Nielsen, J., Sillesen, L: Incidence of chromosome aberration among
11,148 newborn children. Humangenetik 301-12 (1975)
Noël, B., Levy, M., Réthoré, M. O.: Trisomie partielle du bras long
du chromosome 11 par malségrégation dune translocation maternelle
t(11;22)(q23.1;q11.1). Ann. Génét. (Paris) 19, 137-139 (1976)
Pardo, D., Luciani, J. M.; Stahl, A.: Localisation, par hybridation in
situ, des genes des ARN 28 S et 18S dans les chromosomes somatiques humains.
Ann. Génét. (Paris) 18, 105-109 (1975)
Prieur, M., Dutrillaux, B., Rethoré, M. O., Lejeune, J.: Analyse
d'une translocation t(18p+21q-) par dénaturation ménagée. Ann. Génét.
(Paris) 14, 305-307 (1971)
Prieur, M., Dutrillaux, B., Lejeune, J.: Planches descriptives des
chromosomes humains (Analyse en bandes R et nomenclature selon la conférence
de Paris, 1971). Ann. Génét. (Paris) 16, 39-46 (1973)
Prieur, M., Forabosco, A., Dutrillaux, B., Laurent, C., Bernascani,
S., Lejeune, J.: La trisomie 1Oq24 ? qter. Ann. Génét. (Paris) 18,
Raoul, O., Rethoré, M. O., Dutrillaux, B., Michon, L., Lejeune, J.:
Trisomie 14q partielle par translocation maternelle t(10;14)(p15.2;q22). Ann.
Génét. (Paris) 18, 35-39 (1975)
Raoul, O., Carpentier, S., Dutrillaux, B., Mallet, R., Lejeune, J.:
Trisomie partielles du chromosome 21 par translocation maternelle
t(15;21)(q26.2;q21). Ann. Génét. (Paris) 19, 187-190 (1976)
Raoul, O., Dutrillaux, B., See, G., Dayras, J. C., Lejeune, J.:
Trisomie et monosomie pour le bras court du chromosome 18 par translocation
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Raoul, O., Aurias, A., Volkman, H., Michon, L., Lejeune, J.: Trisomie
1q partielle par translocation maternelle t(1;4)(q32.2;q35). Ann. Génét.
(Paris) (in press, 1978b)
Rethoré, M. O., Dutrillaux, B., Baheux, G., Gerveaux, J., Lejeune,
J.: Monosomie pour les regions juxtacentromeriques d'un chromosome 21. Exp.
Cell Res. 70, 455-45b (1972)
Rethoré, M. O., Dutrillaux, B., Lejeune, J.: Translocation
46,XX,t(15;21)(q13;q22.1) chez la mere de deux enfants atteints de trisomie 15
et de monosomie 21 partielles. Ann. Génét. (Paris) 16, 271-275 (1973a)
Rethoré, M. O., Hoehn, H., Rott, H. D., Couturier, J., Dutrillaux,
B., Lejeune, J.; Analyse de la trisomie 9p par dénaturation ménagée. A
propos d'un nouveau cas. Humangenetik 18, 129-138 (1973b)
Rethoré, M. O., Ferrand, J., Dutrillaux, B., Lejeune, J.: Trisomie 9p
par t(4;9)(q34;q21)mat. Ann. Génét. (Paris) 17, 157-161 (1974)
Rethoré M. O., Kaplan, J. C., Junien, CI., Cruvellier, J.,
Dutrillaux, B., Aurias, A., Carpentier, S., Lafourcade, J., Lejeune, J.:
Augmentation de I'activité de la LDH-B chez un garqon trisomique 12p par
malségrégation dune translocation maternelle t(12;14)(q12;p11). Ann. Génét.
(Paris) 18, 81-87 (1975)
Rethoré, M. O., Aurias, A., Couturier, J., Dutrillaux, B., Prieur,
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Ann. Génét. (Paris) 20, 5-11 (1977)
Serville, F., Broustet, A., Peyresblanques, J., Bouineau, J.,:
Anophtalmie bilatérale, anomalies de la face et translocation t(4;14). J.
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Sinet, P. M., Dutrillaux, B., Prieur, M., Lejeune, J.: Rôle des
translocations parentales en cas, de fausses couches a répetition. Rev. Fr.
Gynécol. 68, 655-660 (1973)
Sinet, P. M., Couturier, J., Dutrillaux, B., Poissonnier, M., Raoul,
O., Rethoré, M. O., Allard, D., Lejeune, J., Jérôme, H.: Trisomie 21 et
superoxyde dismutase 1. Exp. Cell Res. 97 47-55 (1976)
Tharapel, A. T., Summit, R. L., Wilroy, R. S., Martens, P.: Apparently
balanced de novo trapslocations in patients with abnormal phenotypes: Report of
6 cases. Clip. Genet, 11, 255-269 (1977)
Turleau, C., Plachot, M., Chavin-Colin, F., Roubin, M., Langmaid, H.,
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Tusques, J., Grislain, J. R., André, M. J., Mainard, R., Rival, J.
M., Cadudal, J. L., DutrilIaux, B., Lejeune, J.: Trisomie partielle 11q
identifiée grâce à l'étude en " dénaturation ménagée " par la chaleur, de
la translocation équilibrée paternelle. Ann. Génét. (Paris) 15, 167-172
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pour le Doctorat d'Etat en Médecine. Université Bordeaux II 1977
Walzer, S., Gerald, P. S.: Chromosome abnormalities in 11,154 newborn
infants. Am. J. Hum. Genet. 24, 38a (No. 6, Part I) (1972)