Putative non-Mendelian transmission of retinoblastoma in males: a phenotypic segregation analysis of 150 pedigrees

• Published in: Human genetics Vol. 94; no. 5; p. 484
• Main Authors: Munier, F L, Arabien, L, Flodman, P, Spence, M A, Pescia, G, Rutz, H P, Murphree, A L
• Format: Journal Article
• Language: English
• Published: Germany 01.11.1994
• Subjects: Female; Genes, Retinoblastoma - genetics; Genetic Linkage; Heterozygote; Humans; Likelihood Functions; Male; Pedigree; Phenotype; Retinoblastoma - genetics; Retrospective Studies; Sex Factors; Sex Ratio
• ISSN: 0340-6717
• DOI: 10.1007/BF00211012

In a previous genotypic study of eight families, we described paternal segregation distortion favoring the transmission of mutant alleles at the retinoblastoma gene locus (RB1). In the current study, we reviewed 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 that 49.1% of the offspring of male transmitters were affected, while 44.3% of the offspring of female transmitters were affected. While this difference is not statistically significant, it is consistent with the previous findings. No significant sex distortion could be detected among the progeny of carrier fathers and mothers. In order to quantify the transmission ratio more precisely further prospective molecular genetic analysis is warranted. We propose a biological mechanism to account for a putative segregation distortion, namely that genetic recombination creates clones of spermatogonia that are homozygous for the mutant RB1 allele leading to a non-Mendelian ratio of sperm. This model can be experimentally tested using amplification of DNA from single sperm cells.