SOMATIC MOSAICISM IN SPERM IS ASSOCIATED WITH INTERGENERATIONAL (CAG)(N) CHANGES IN HUNTINGTON DISEASE

被引：68
作者：
TELENIUS, H
ALMQVIST, E
KREMER, B
SPENCE, N
SQUITIERI, F
NICHOL, K
GRANDELL, U
STARR, E
BENJAMIN, C
CASTALDO, I
CALABRESE, O
ANVRET, M
GOLDBERG, YP
HAYDEN, MR
机构：
[1] UNIV BRITISH COLUMBIA,DEPT MED GENET,VANCOUVER,BC V6T 1Z4,CANADA
[2] KAROLINSKA INST,HUDDINGE HOSP,DEPT GERIATR MED,S-14186 HUDDINGE,SWEDEN
[3] KAROLINSKA INST,DEPT MOLEC MED,STOCKHOLM,SWEDEN
[4] ACAD HOSP,DEPT NEUROL,NIJMEGEN,NETHERLANDS
[5] UNIV NAPLES FEDERICO II,DEPT CELLULAR & MOLEC BIOL & PATHOL,NAPLES,ITALY
来源：
HUMAN MOLECULAR GENETICS | 1995年 / 4卷 / 02期
基金：
英国医学研究理事会;
关键词：
D O I：
10.1093/hmg/4.2.189
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
We have analysed the CAG repeat in the Huntington disease (HD) gene in sperm and blood from 20 unrelated HD patients. Although the CAG repeat displayed significant mosaicism in sperm from all individuals, there were marked differences in the degree of repeat instability. Individuals who had either inherited or transmitted an expanded CAG repeat displayed the highest revels of repeat mosaicism, whereas individuals who had inherited or transmitted a contracted repeat had very limited CAG mosaicism in sperm. A strong association between intergenerational change in CAG allele size and the level of sperm repeat mosaicism was determined (P = 0.019). In contrast, neither blood CAG size nor repeat mosaicism in blood, were significantly associated with intergenerational CAG changes. These data suggest the presence of a cis-acting factor, separate from CAG size, that strongly influences the intergenerational behaviour of the CAG repeat. Additional studies are needed to determine whether analysis of CAG mosaicism in sperm is useful for assessing an individual's risk for transmitting large expansions or contractions to his offspring.
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页码：189 / 195
页数：7
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