Vastly higher rate of de novo- spontaneous mutations in males than in females

Am J Hum Genet. 1996 June; 58(6): 1364–1368.
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High male:female ratio of germ-line mutations: an alternative explanation for postulated gestational lethality in males in X-linked dominant disorders.
G. H. Thomas
Department of Pediatrics, The John Hopkins University School of Medicine, Baltimore, MD, USA.


In this paper I suggest that a vastly higher rate of de novo mutations in males than in females would explain some, if not most, X-linked dominant disorders associated with a low incidence of affected males


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The germline mutation rates between the sexes within a species are largely influenced by germ cell divisions per generation.


Environ Mol Mutagen. 1995;25 Suppl 26:48-64.
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Biological basis of germline mutation: comparisons of spontaneous germline mutation rates among drosophila, mouse, and human.
Drost JB, Lee WR.
Institute for Mutagenesis, Louisiana State University, Baton Rouge 70803-1725, USA.
Spontaneous mutation rates per generation are similar among the three species considered here--Drosophila, mouse, and human--and are not related to time, as is often assumed. Spontaneous germline mutation rates per generation averaged among loci are less variable among species than they are among loci and tests and between gender. Mutation rates are highly variable over time in diverse lineages. Recent estimates of the number of germ cell divisions per generation are: for humans, 401 (30-year generation) in males and 31 in females; for mice, 62 (9-month generation) in males and 25 in females; and for Drosophila melanogaster, 35.5 (18-day generation) in males and 36.5 (25-day generation) in females. The relationships between germ cell division estimates of the two sexes in the three species closely reflect those between mutation rates in the sexes, although mutation rates per cell division vary among species. Whereas the overall rate per generation is constant among species, this consistency must be achieved by diverse mechanisms. Modifiers of mutation rates, on which selection might act, include germline characteristics that contribute disproportionately to the total mutation rates. The germline mutation rates between the sexes within a species are largely influenced by germ cell divisions per generation. Also, a large portion of the total mutations occur during the interval between the beginning of meiosis and differentiation of the soma from the germline. Significant genetic events contributing to mutations during this time may include meiosis, lack of DNA repair in sperm cells, methylation of CpG dinucleotides in mammalian sperm and early embryo, gonomeric fertilization, and rapid cleavage divisions.
PMID: 7789362 [PubMed - indexed for MEDLINE]