Age and sex effects on human mutation rates: an old problem with new complexities

Base substitution mutations are far more common in human males than in females, and the frequency increases with paternal age. Both can be accounted for by the greater number of pre-meiotic cell divisions in males, especially old ones. In contrast, small deletions do not show any important age effec...

Full description

Saved in:
Bibliographic Details
Published in:Journal of radiation research 2006, Vol.47 Suppl B (1), p.B75-B82
Main Author: Crow, James F
Format: Article
Language:English
Subjects:
Adolescent
Adult
Age Factors
Child
Child, Preschool
Female
Gene mutations
Genetic aspects
Humans
Infant
Infant, Newborn
Male
Meiosis - genetics
Middle Aged
Models, Genetic
Mutation
Paternal Age
Physiological aspects
Polymorphism, Single Nucleotide
Pregnancy
Selection, Genetic
Sex Characteristics
Spermatozoa - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Base substitution mutations are far more common in human males than in females, and the frequency increases with paternal age. Both can be accounted for by the greater number of pre-meiotic cell divisions in males, especially old ones. In contrast, small deletions do not show any important age effect and occur with approximately equal frequency in the two sexes. Mutations in most genes include both types, and the sex and paternal age effect depends on the proportion of the two types. A few traits, of which Apert Syndrome is best understood, are mutation hot spots with all the mutations occurring in one or two codons, usually at one nucleotide. They occur with very high frequency almost exclusively in males and the frequency increases rapidly with paternal age. It has been suggested that the mutant cells have a selective advantage in the male germ-line prior to meiosis. Evidence for this surprising, but important, hypothesis is discussed. A possible mechanism is the conversion of asymmetrical stem-cell divisions into symmetric ones. Some traits with complex etiology show a slight paternal age effect. There is also a short discussion of the high deleterious mutation rate and the role of sexual reproduction in reducing the consequent mutation load.
ISSN:0449-3060
1349-9157
DOI:10.1269/jrr.47.b75