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Title: Sex-dependent mechanisms for expansions and contractions of the CAG repeat on affected Huntington disease chromosomes

Abstract

A total of 254 affected parent-child pairs with Huntington disease (HD) and 440 parent-child pairs with CAG size in the normal range were assessed to determine the nature and frequency of intergenerational CAG changes in the HD gene. Intergenerational CAG changes are extremely rare (3/440 [0.68%]) on normal chromosomes. In contrast, on HD chromosomes, changes in CAG size occur in {approximately}70% of meioses on HD chromosomes, with expansions accounting for 73% of these changes. These intergenerational CAG changes make a significant but minor contribution to changes in age at onset (r{sup 2}=.19). The size of the CAG repeat influenced larger intergenerational expansions (>7 CAG repeats), but the likelihood of smaller expansions or contractions was not influenced by CAG size. Large expansions (>7 CAG repeats) occur almost exclusively through paternal transmission (0.96%; P<10{sub -7}), while offspring of affected mothers are more likely to show no change (P=.01) or contractions in CAG size (P=.002). This study demonstrates that sex of the transmitting parent is the major determinant for CAG intergenerational changes in the HD gene. Similar paternal sex effects are seen in the evolution of new mutations for HD from intermediate alleles and for large expansions on affected chromosomes. Affected mothers almostmore » never transmit a significantly expanded CAG repeat, despite the fact that many have similar large-sized alleles, compared with affected fathers. The sex-dependent effects of major expansion and contractions of the CAG repeat in the HD gene implicate different effects of gametogenesis, in males versus females, on intergenerational CAG repeat stability. 22 refs., 4 figs., 3 tabs.« less

Authors:
; ;  [1]
  1. Univ. of British Columbia, Vancouver (Canada); and others
Publication Date:
OSTI Identifier:
105242
Resource Type:
Journal Article
Journal Name:
American Journal of Human Genetics
Additional Journal Information:
Journal Volume: 57; Journal Issue: 2; Other Information: PBD: Aug 1995
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; HUMAN CHROMOSOMES; CHROMOSOMAL ABERRATIONS; SEX DEPENDENCE; PATIENTS; HEREDITARY DISEASES; GENES; GENE MUTATIONS; NUCLEOTIDES; SIZE; STABILITY; ANIMAL CELLS; MEIOSIS; GAMETOGENESIS; POLYMERASE CHAIN REACTION; STATISTICS

Citation Formats

Kremer, B, Theilmann, J, and Spence, N. Sex-dependent mechanisms for expansions and contractions of the CAG repeat on affected Huntington disease chromosomes. United States: N. p., 1995. Web.
Kremer, B, Theilmann, J, & Spence, N. Sex-dependent mechanisms for expansions and contractions of the CAG repeat on affected Huntington disease chromosomes. United States.
Kremer, B, Theilmann, J, and Spence, N. 1995. "Sex-dependent mechanisms for expansions and contractions of the CAG repeat on affected Huntington disease chromosomes". United States.
@article{osti_105242,
title = {Sex-dependent mechanisms for expansions and contractions of the CAG repeat on affected Huntington disease chromosomes},
author = {Kremer, B and Theilmann, J and Spence, N},
abstractNote = {A total of 254 affected parent-child pairs with Huntington disease (HD) and 440 parent-child pairs with CAG size in the normal range were assessed to determine the nature and frequency of intergenerational CAG changes in the HD gene. Intergenerational CAG changes are extremely rare (3/440 [0.68%]) on normal chromosomes. In contrast, on HD chromosomes, changes in CAG size occur in {approximately}70% of meioses on HD chromosomes, with expansions accounting for 73% of these changes. These intergenerational CAG changes make a significant but minor contribution to changes in age at onset (r{sup 2}=.19). The size of the CAG repeat influenced larger intergenerational expansions (>7 CAG repeats), but the likelihood of smaller expansions or contractions was not influenced by CAG size. Large expansions (>7 CAG repeats) occur almost exclusively through paternal transmission (0.96%; P<10{sub -7}), while offspring of affected mothers are more likely to show no change (P=.01) or contractions in CAG size (P=.002). This study demonstrates that sex of the transmitting parent is the major determinant for CAG intergenerational changes in the HD gene. Similar paternal sex effects are seen in the evolution of new mutations for HD from intermediate alleles and for large expansions on affected chromosomes. Affected mothers almost never transmit a significantly expanded CAG repeat, despite the fact that many have similar large-sized alleles, compared with affected fathers. The sex-dependent effects of major expansion and contractions of the CAG repeat in the HD gene implicate different effects of gametogenesis, in males versus females, on intergenerational CAG repeat stability. 22 refs., 4 figs., 3 tabs.},
doi = {},
url = {https://www.osti.gov/biblio/105242}, journal = {American Journal of Human Genetics},
number = 2,
volume = 57,
place = {United States},
year = {Tue Aug 01 00:00:00 EDT 1995},
month = {Tue Aug 01 00:00:00 EDT 1995}
}