Mutation rates in humans. I. Overall and sex-specific rates obtained from a population study of hemophilia B.

Abstract:

:A population-based study of hemophilia B mutations was conducted in the United Kingdom in order to construct a national confidential database of mutations and pedigrees to be used for the provision of carrier and prenatal diagnoses based on mutation detection. This allowed the direct estimate of overall (micro), male (v), and female (u) mutation rates for hemophilia B. The values obtained per gamete per generation and the 95% confidence intervals are micro;=7.73 (6. 29-9.12&parr0;x10-6; v=18.8 (14.5-22.9&parr0;x10-6; and u=2.18 (1. 44-3.16&parr0;x10-6. The ratio of male-to-female mutation rates is 8. 64, with a 95% confidence interval of 5.46-14.5. The higher male rate was not caused by a much higher rate of transition at CpG sites in the male. Attempts to detect evidence of gonadal mosaicism for hemophilia B mutation in suitable families did not detect any instances of ovarian mosaicism in any of 47 available opportunities. This suggests that the risk of a noncarrier mother manifesting as a gonadal mosaic by transmitting the mutation to a second child should be <0.062.

journal_name

Am J Hum Genet

authors

Green PM,Saad S,Lewis CM,Giannelli F

doi

10.1086/302651

subject

Has Abstract

pub_date

1999-12-01 00:00:00

pages

1572-9

issue

6

eissn

0002-9297

issn

1537-6605

pii

S0002-9297(07)63576-9

journal_volume

65

pub_type

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