Advanced

Direct estimate of the haemophilia B (factor IX deficiency) mutation rate and of the ratio of the sex-specific mutation rates in Sweden

Montandon, A. J.; Green, P. M.; Bentley, D. R.; Ljung, R. LU ; Kling, S. LU ; Nilsson, I. M. and Giannelli, F. (1992) In Human Genetics 89(3). p.319-322
Abstract

Mutation rates for X-linked recessive diseases have so far been estimated indirectly by postulating an equilibrium between the loss of defective genes caused by the low reproductive fitness of affected males and the gain resulting from new mutations. Here, for the first time, we directly estimate both the overall and sex-specific mutation rates for haemophilia B by detecting the gene defect of the families registered at the Malmö Haemophilia Centre. These represent a complete sample of the Swedish haemophilia B population (45 out of 77 pedigrees) and contain 23 families with a single affected male. Fifteen of these males had mothers available for study, and of these mothers, 13 had parents available for study. We show that 3 of the... (More)

Mutation rates for X-linked recessive diseases have so far been estimated indirectly by postulating an equilibrium between the loss of defective genes caused by the low reproductive fitness of affected males and the gain resulting from new mutations. Here, for the first time, we directly estimate both the overall and sex-specific mutation rates for haemophilia B by detecting the gene defect of the families registered at the Malmö Haemophilia Centre. These represent a complete sample of the Swedish haemophilia B population (45 out of 77 pedigrees) and contain 23 families with a single affected male. Fifteen of these males had mothers available for study, and of these mothers, 13 had parents available for study. We show that 3 of the above patients and 10 of their mothers carry new mutations, and by extrapolation calculate that 8 males and 98 females should carry new haemophilia B mutations in the Swedish population (8.52 × 106 individuals). This leads to the following estimate of the mutation rates: overall μ = 4.1 × 10-6; male specific v = 2.1 × 10-5; and female specific u = 1.9 × 10-6. The ratio of such male to female specific mutation rates is thus v/u = 11. © 1992 Springer-Verlag.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Genetics
volume
89
issue
3
pages
4 pages
publisher
Springer
external identifiers
  • Scopus:0026664109
ISSN
0340-6717
DOI
10.1007/BF00220550
language
English
LU publication?
yes
id
57046e7b-bd99-4405-8b16-3816d5f87c7f
date added to LUP
2016-11-17 10:25:33
date last changed
2016-11-17 10:25:33
@misc{57046e7b-bd99-4405-8b16-3816d5f87c7f,
  abstract     = {<p>Mutation rates for X-linked recessive diseases have so far been estimated indirectly by postulating an equilibrium between the loss of defective genes caused by the low reproductive fitness of affected males and the gain resulting from new mutations. Here, for the first time, we directly estimate both the overall and sex-specific mutation rates for haemophilia B by detecting the gene defect of the families registered at the Malmö Haemophilia Centre. These represent a complete sample of the Swedish haemophilia B population (45 out of 77 pedigrees) and contain 23 families with a single affected male. Fifteen of these males had mothers available for study, and of these mothers, 13 had parents available for study. We show that 3 of the above patients and 10 of their mothers carry new mutations, and by extrapolation calculate that 8 males and 98 females should carry new haemophilia B mutations in the Swedish population (8.52 × 10<sup>6</sup> individuals). This leads to the following estimate of the mutation rates: overall μ = 4.1 × 10<sup>-6</sup>; male specific v = 2.1 × 10<sup>-5</sup>; and female specific u = 1.9 × 10<sup>-6</sup>. The ratio of such male to female specific mutation rates is thus v/u = 11. © 1992 Springer-Verlag.</p>},
  author       = {Montandon, A. J. and Green, P. M. and Bentley, D. R. and Ljung, R. and Kling, S. and Nilsson, I. M. and Giannelli, F.},
  issn         = {0340-6717},
  language     = {eng},
  number       = {3},
  pages        = {319--322},
  publisher    = {ARRAY(0x84d3978)},
  series       = {Human Genetics},
  title        = {Direct estimate of the haemophilia B (factor IX deficiency) mutation rate and of the ratio of the sex-specific mutation rates in Sweden},
  url          = {http://dx.doi.org/10.1007/BF00220550},
  volume       = {89},
  year         = {1992},
}