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FRAXA and FRAXE: evidence against segregation distortion and for an effect of intermediate alleles on learning disability

FRAXA and FRAXE: evidence against segregation distortion and for an effect of intermediate alleles on learning disability
FRAXA and FRAXE: evidence against segregation distortion and for an effect of intermediate alleles on learning disability
There have been several claims of segregation distortion (meiotic drive) for loci associated with diseases caused by trinucleotide repeats, leading us to test for this phenomenon in a large study of the X-linked loci FRAXA and FRAXE. We found no evidence of meiotic drive in females and no convincing evidence in males, where the limitation of risk to daughters creates a testing bias for alleles of interest. Alleles for pre- and full mutation, intermediate alleles, and common alleles were analyzed separately, with the same negative results that are extended in the discussion to claims of meiotic drive for other diseases. On the other hand, an excess risk of learning difficulties was confirmed for intermediate FRAXA alleles (relative risk, 2.58 ± .74) and suggested for intermediate FRAXE alleles. The penetrance of learning difficulty is low, the risk being estimated as .039 for FRAXA common alleles and .101 for intermediate alleles. Because of their lower gene frequency, full mutations are a less frequent cause of learning difficulty than intermediate alleles, which contribute .0020 to total prevalence and .0012 to attributable prevalence of learning difficulty
0027-8424
719-724
Teague, J.W.
481bf04e-9cd4-4acf-8824-2a5f7cfc9dca
Morton, N.E.
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Dennis, N.R.
154aa617-52e2-4711-98ef-89fef8610de7
Curtis, G.
ae45c3b6-dbda-45c8-9634-bfdb6407165f
McKechnie, N.
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Macpherson, J.N.
ef609e90-d688-4129-894c-f841ab3f2c29
Murray, A.
d80b2bea-5bde-448f-a1d2-c5627db1df99
Pound, M.C.
86ebbb55-760a-49d8-baab-70757e597fe3
Sharrock, A.J.
b2373510-f591-42fd-a3b7-f79987065831
Youings, S.A.
aeefe8ed-0699-41bf-95d6-8d5130b8053b
Jacobs, P A.
44455930-44a8-496b-86b9-4ef6c0706ab4
Teague, J.W.
481bf04e-9cd4-4acf-8824-2a5f7cfc9dca
Morton, N.E.
eec59d23-d341-41fd-b275-331eb06c3abb
Dennis, N.R.
154aa617-52e2-4711-98ef-89fef8610de7
Curtis, G.
ae45c3b6-dbda-45c8-9634-bfdb6407165f
McKechnie, N.
5e2965eb-638f-4eaf-adaa-93c1559f5e46
Macpherson, J.N.
ef609e90-d688-4129-894c-f841ab3f2c29
Murray, A.
d80b2bea-5bde-448f-a1d2-c5627db1df99
Pound, M.C.
86ebbb55-760a-49d8-baab-70757e597fe3
Sharrock, A.J.
b2373510-f591-42fd-a3b7-f79987065831
Youings, S.A.
aeefe8ed-0699-41bf-95d6-8d5130b8053b
Jacobs, P A.
44455930-44a8-496b-86b9-4ef6c0706ab4

Teague, J.W., Morton, N.E., Dennis, N.R., Curtis, G., McKechnie, N., Macpherson, J.N., Murray, A., Pound, M.C., Sharrock, A.J., Youings, S.A. and Jacobs, P A. (1998) FRAXA and FRAXE: evidence against segregation distortion and for an effect of intermediate alleles on learning disability. Proceedings of the National Academy of Sciences, 95 (2), 719-724. (doi:10.1073/pnas.95.2.719). (PMID:9435259)

Record type: Article

Abstract

There have been several claims of segregation distortion (meiotic drive) for loci associated with diseases caused by trinucleotide repeats, leading us to test for this phenomenon in a large study of the X-linked loci FRAXA and FRAXE. We found no evidence of meiotic drive in females and no convincing evidence in males, where the limitation of risk to daughters creates a testing bias for alleles of interest. Alleles for pre- and full mutation, intermediate alleles, and common alleles were analyzed separately, with the same negative results that are extended in the discussion to claims of meiotic drive for other diseases. On the other hand, an excess risk of learning difficulties was confirmed for intermediate FRAXA alleles (relative risk, 2.58 ± .74) and suggested for intermediate FRAXE alleles. The penetrance of learning difficulty is low, the risk being estimated as .039 for FRAXA common alleles and .101 for intermediate alleles. Because of their lower gene frequency, full mutations are a less frequent cause of learning difficulty than intermediate alleles, which contribute .0020 to total prevalence and .0012 to attributable prevalence of learning difficulty

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Published date: January 1998
Organisations: Faculty of Health Sciences

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Local EPrints ID: 366290
URI: http://eprints.soton.ac.uk/id/eprint/366290
ISSN: 0027-8424
PURE UUID: 4491efdc-223a-4240-b005-f6ce916b3f29

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Date deposited: 07 Jul 2014 08:07
Last modified: 16 Jul 2019 21:02

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Contributors

Author: J.W. Teague
Author: N.E. Morton
Author: N.R. Dennis
Author: G. Curtis
Author: N. McKechnie
Author: J.N. Macpherson
Author: A. Murray
Author: M.C. Pound
Author: A.J. Sharrock
Author: S.A. Youings
Author: P A. Jacobs

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