Reciprocal Translocations in Human Populations A Preliminary Analysis


Pfizer Medical Monographs 5 Human Population Cytogenetics Edinburgh University Press 1970.


The Genetic equilibrium of reciprocal translocations in man is difficult to assess because of the fundamental biases in the detection of carriers.

The great majority of recorded reciprocal translocations have been found because one child received an unbalanced genome through malsegregation of the translocation, and only 3 of the reported families [1, 6, 43] have been ascertained randomly. In two others [25, 37], the proband was affected by a sex chromosome aberration. Hence any attempt to analyse the genetic fitness of balanced translocations must take into account the biases of ascertainment, a rather difficult task considering the scarcity of data. Many different translocations have been found but the data on any particular translocation is insufficient to assess its genetic fitness. We therefore decided to pool all published data [ 1-48] together with our personal observations [49-50], deliberately putting together different types of translocations in an attempt to get an over all impression. Only families where a translocation carrier has more than one child have been considered. Centric fusions between acrocentrics have not been included in this study.

At least one example of a partial trisomy has been retarded for each group of chromosomes, except the F group. Propositi with the partial monosomies, 5p- , 18p- , 18q- and Dq- have also been found.

In order to estimate the segregation ratio, two approaches can be made with this material:

(i) an estimation of the risk of malsegregation in the progeny of trapslocation carriers,

(ii) an estimation of the ratio of normal karyotypes to translocation carriers amongst the phenotypically normal descendants of carriers.


(i) Risk of malsegregation


(A) Children born from a carrier mother.

The overall sample includes 80 sibships containing 69 affected persons with an unbalanced karyotype in a total of 268 children. The net frequency of affected individuals is thus 0.26. Three main biases affect this figure:

(1) All the families include at least one affected child (truncated distribution).

(2) The probability of ascertainment is related to the actual number of affected individuals (multiple selection).

(3) Malsegregations resulting in non-viable zygotes are not included in this survey (bias impossible to assess).

The overall sample can be split up into subsamples in order to apply statistical corrections

(a) Sibships of probands born from a carrier mother.

There are 136 children including 58 affected persons in a total of 43 sibships.

The multiple selection equation is

N = number of sibships

R = number of affected children

T = total number of children

p1 = estimated proportion of affected children.

This gives p1= 0,161 ± 0,038.

This value does not agree with the value obtained by application of the truncated binomial according to the Haldane formula [52] for which p2 = 0.2587 ± 0.0527

This indicates that bias no. 1 (at least one child affected) is not the only one operating but that multiple selection is also occurring ( bias no. 2 ).

(b) Other sibships excluding the sibships of the probands.

There are 132 children, of whom eleven are affected P3 = 0.083 ± 0.032

We can split the sample into two parts. In the sibships born from a carrier grandmother or great-grandmother of a proband, we find 4 affected out of 72 children (i.e. p4 = 0.056 ± 0.028 ) . This estimate is too low because of the necessary inclusion of the carrier (the parent of the proband).

The second subsample consists of sibships born from carrier aunts, great-aunts or female cousins of a proband. There are 7 affected out of 60 children, i.e. P5 = 0.117 ± 0.041 . This is likely to be the least biased estimate for the whole sample.

It must be remarked that p5 = 0.117 ± 0.041 does not differ significantly from the estimate (after the correction for multiple selection) for the sibships of the probands : p1= 0.161 ± 0.038.


(B) Children born from a carrier father.

The whole sample consists of 34 sibships giving a total of 96 children, of which 21 are affected (i.e. P = 0.22).

The same analysis can be performed:

(a) Sibships of probands born from a carrier father.

The multiple selection equation gives a value of p1 = 0.091 + 0.062.

The truncated binomial would give p2 = 0.380 ± 0.037 and, as noted for the carrier mothers, this discrepancy indicates that multiple selection is playing the major role.

(b) Other sibships excluding the sibships of probands.

If the sibships of the probands are excluded then the rest of the sample is limited to the sibships born from a carrier uncle, great-uncle or cousin of a proband, and p3 = 2/24 = 0.083 ± 0.053


Empirical risk of malsegregation

From the data it can be surmised that the risk to the progeny of carrier mothers is of the order of 0.20 to of 0.10. The risk to the progeny of carrier fathers is probably less. This difference, however, seems less pronounced than in the case of centric fusions [51]. This difference between the sexes is also indicated by the fact that the carrier parent is the mother of the proband in 43 cases, and the father in 13 cases.


(ii) Segregation ratio in phenotypically normal persons

The maintenance of a balanced translocation in a given population can be due either to mutational pressure or to a selective advantage by the carriers. Cases arising from non-carrier parents prove abundantly that mutation pressure is strong, but it is difficult to measure. A selective advantage could result from two kinds of effects in the progeny of heterozygotes:

(1) carriers have more children than normal people.

(2) the translocation is more often transmitted than the normal karyotype. The first hypothesis is difficult to assess because all the families recorded contain at least two children: i.e. childless families and one-child families are not analysed. However, the segregation of the translocation among phenotypically normal persons can be directly analysed.

The whole sample of children born from a carrier parent includes 145 carriers and 101 normals. This segregation differs significantly from the expected 1 : 1 ratio (?2 = 7.86 for ?= 1). However, here also ascertainment is heavily biased, and statistical corrections are necessary and must be adapted to each subsample.

Sibships of the carrier parent of a proband. Of 54 persons born to a carrier female ancestor, there are 37 carriers and 17 normal. Of 27 persons born to a carrier male ancestor there are 20 carriers and 7 normals.

Application of the truncated binomial (since the carrier parent is included by necessity), gives an estimate higher than p = 0.60 which is beyond the range of the published tables. This could indicate a preferential transmission of the translocation, but it can be assumed that, in this subsample, the bias is large not only because of the inclusion of at least one carrier in each sibship, but also because the likelihood of recording the family is effectively much greater if there are many carriers than if there are few.

Hence an application of the multiple selection equation is valid and gives p = 0.528 ± 0.083 for the progeny of a female carrier ancestor and p = 0.588 + 0.119 for the progeny of a male carrier ancestor. These two estimates do not differ significantly from each other and are fully compatible with an expected 1 : 1 segregation among phenotypically normal persons. In othe

In other sibships in which the ascertainment is very close to random, as far as the translocation in phenotypically normal persons is considered, we find:

Progeny of a carrier mother, including phenotypically normal children in the sibships of probands and the sibships of aunts, great-aunts and female cousins of the probands:

p = 52/106 = 0.49 ± 0.047

Progeny of a carrier father, including phenotypically normal children in the sibships of probands and in the sibships of uncles, great-uncles and male cousins of probands:

p = 20/39 = 0.51 ± 0.08

These two values are in agreement with a 1 : 1 segregation ratio and this is the most bias-free sample we can utilise.

A final remark concerns the distribution of sexes. Among the carrier children there are 54 males and 74 females but among the normale, there are 48 males and 47 females. This apparently curious sex ratio does not depart significantly from homogeneity (?2 = 1.52 for ?= 1). However, the multiple ascertainment bias and other possible mechanisms which could explain this tendency require further investigation.



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