PUTATIVE NON-MENDELIAN TRANSMISSION OF RETINOBLASTOMA IN MALES - A PHENOTYPIC SEGREGATION ANALYSIS OF 150 PEDIGREES

In a previous genotypic study of eight families, we discribed paternal segregation distortion favoring the transmission of mutant alleles at the retinoblastoma gene locus (RB1). In the current study, we reviewe d all published retinoblastoma pedigrees with defined ascertainment (n = 150), to determine whether the phenotypic segregation frequency at the RB1 locus is in general influenced by the sex of the transmitting parent. Segregation analysis under complete ascertainment revealed tha t 49.1% of the offspring of male transmitters were affected, while 44. 3% of the offspring of female transmitters were affected. While this d ifference is not statistically significant, it is consistent with the previous findings. No significant sex distortion could be detected amo ng the progeny of carrier fathers and mothers. In order to quantify th e transmission ratio more precisely further prospective molecular gene tic analysis is warranted. We propose a biological mechanism to accoun t for a putative segregation distortion, namely that genetic recombina tion creates clones of spermatogonia that are homozygous for the mutan t RBI allele leading to a non-Mendelian ratio of sperm. This model can be experimentally tested using amplification of DNA from single sperm cells.