VARIATION OF THE CGG REPEAT AT THE FRAGILE-X SITE RESULTS IN GENETIC INSTABILITY - RESOLUTION OF THE SHERMAN PARADOX

被引:1710
作者
FU, YH
KUHL, DPA
PIZZUTI, A
PIERETTI, M
SUTCLIFFE, JS
RICHARDS, S
VERKERK, AJMH
HOLDEN, JJA
FENWICK, RG
WARREN, ST
OOSTRA, BA
NELSON, DL
CASKEY, CT
机构
[1] EMORY UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT BIOCHEM,ATLANTA,GA 30322
[2] EMORY UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT PEDIAT,ATLANTA,GA 30322
[3] ERASMUS UNIV,DEPT CELL BIOL,3000 DR ROTTERDAM,NETHERLANDS
[4] QUEENS UNIV,DEPT CYTOGENET,KINGSTON K7L 3N6,ONTARIO,CANADA
关键词
D O I
10.1016/0092-8674(91)90283-5
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
Fragile X syndrome results from mutations in a (CGG)n repeat found in the coding sequence of the FMR-1 gene. Analysis of length variation in this region in normal individuals shows a range of allele sizes varying from a low of 6 to a high of 54 repeats. Premutations showing no phenotypic effect in fragile X families range in size from 52 to over 200 repeats. All alleles with greater than 52 repeats, including those identified in a normal family, are meiotically unstable with a mutation frequency of one, while 75 meioses of alleles of 46 repeats and below have shown no mutation. Premutation alleles are also mitotically unstable as mosaicism is observed. The risk of expansion during oogenesis to the full mutation associated with mental retardation increases with the number of repeats, and this variation in risk accounts for the Sherman paradox.
引用
收藏
页码:1047 / 1058
页数:12
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