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

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Abstract

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 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.

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  1. F. L. Munier

    Present address: Département d'Ophtamologie, Faculté de Médecine de l'Université de Lausanne, Hôpital Jules Gonin, Avenue de France 15, CH-1004, Lausanne, Switzerland

Authors and Affiliations

  1. Division of Ophthalmology, Childrens Hospital Los Angeles, and the Departments of Ophthalmology and Pediatrics, University of Southern California School of Medicine, 90027, Los Angeles, CA, USA

    F. L. Munier & A. L. Murphree

  2. Division of Human Genetics and Birth Defects, Department of Pediatrics, University of California Irvine Medical Center, 92613-1491, Orange, CA, USA

    L. Arabian, P. Flodman & M. A. Spence

  3. Division of Medical Genetics, Department of Pediatrics, Centre Hospitalier Universitaire Vaudois, CH-1011, Lausanne, Switzerland

    G. Pescia

  4. Department of Internal Medicine, and Laboratory of Radiobiology, Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, CH-1011, Lausanne, Switzerland

    H. P. Rutz

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Munier, F.L., Murphree, A.L., Arabian, L. et al. Putative non-Mendelian transmission of retinoblastoma in males: a phenotypic segregation analysis of 150 pedigrees. Hum Genet 94, 484–490 (1994). https://doi.org/10.1007/BF00211012

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