Autoradiographic studies on an X-autosomal translocation in man: 45, X,15–, tan(15qXq+)+

Abstract

In a female infant exhibiting cleft palate, hydrocephalus communicans, vitium cordis congenitum, and other anomalies, chromosome analysis revealed a C/D translocation. According to its replication pattern, the translocation chromosome comprised almost a whole X and the long arm of a chromosome 15. In accordance with the Lyon-hypothesis, in a number of the cells the translocated X, X_t, or the normal X, X_n, was the late-replicating chromosome. In a few cells both X_t and X_n were late labeled, which was interpreted as perhaps the result of somatic segregation. In some of the cells showing a late-replicating X_t, the autosomal segment, which is normally early replicating, was labeled; this observation was interpreted as a position effect. The genetic material lost comprised the product of the reciprocal translocation, consisting of the centromeric region of chromosome 15 and the telomeric region of the long arm of the X. The severe clinical anomalies of the patient were ascribed to the inactivation of the translocated autosomal segment observed in a part of the examined cells.

Two Human X-Autosome Translocations Identified by Autoradiography and Fluorescence

“…In the first patient, X- [16] 46,X,t (Xq+;? ) Xt late replicating (75%); [22] Xn late replicating (11%); both Xt and Xn late replicating (10%) chromosomal material has been placed onto an autosome (no. 9), while patient no.…”

“…2). In two other patients, either the entire Xt or the Xn was late replicating in different proportions (random inactivation) [21,22]. These nine cases may be analogous to the X-autosome translocations which show variability of inactivation in the mouse [29,30].…”

“…2). Those cases showing a possible random pattern of late replication may consist of autosomal segments translocated close enough to the inactivation center so as to become inactivated [21,22]. However, if the translocations in these cases were reciprocal and the genome balanced, the rearranged X chromosome might also be functional, as in those cases in table 1, and random inactivation might occur as in normal cells.…”

“…Perhaps the strongest evidence in favor of the "inactivation center" hypothesis is gained from those cases which showed apparent random inactivation of either Xn or Xt with multiple congenital anomalies [21,22]. That either X chromosome may be late replicating suggests normal genetic activity for both X chromosomes and a "balanced" genome, as in those cases of table 1 [21 ], who has the long arm of a no.…”

“…These anomalies have been interpreted by the authors as not due to the loss of genetic material, since the karyotype appears morphologically balanced, but rather attributed to genetic inactivation of the translocated autosomal segment of the 18q by a "spreading effect." The case of Engel et al [22] illustrates late DNA replication of the autosomal segment (no. 15) which has been translocated to the X chromosome when the Xt is inactivated.…”