PRECURSOR ARRAYS FOR TRIPLET REPEAT EXPANSION AT THE FRAGILE-X LOCUS

被引：120

作者：

HIRST, MC ^{[1
]}

GREWAL, PK ^{[1
]}

DAVIES, KE ^{[1
]}

机构：

[1] JOHN RADCLIFFE HOSP,INST MOLEC MED,MOLEC GENET GRP,OXFORD OX3 9DU,ENGLAND

来源：

HUMAN MOLECULAR GENETICS | 1994年 / 3卷 / 09期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

D O I：

10.1093/hmg/3.9.1553

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：

To determine factors governing triplet repeat expansion at FMR1, we need to understand the basis of normal variation. We have sequenced the FMR1 repeat from 102 normal X chromosomes and show that most are interrupted with a regularly spaced AGG trinucleotide giving an ordered structure to the array. Five types of arrays were identified consisting of varying numbers of a core unit with consensus [AGG(CGG)(9)]. Additional variation in the length of the (CGG)(n) portion within each unit generates the continuum of lengths seen on normal chromosomes. Ten per cent contain long, uninterrupted tracts of (CGG)(n), and their lengths suggest they have arisen by the loss of AGG triplets from longer interrupted arrays. Haplotype analysis of arrays carrying long, uninterrupted (CGG)(n) tracts suggests that they occur more frequently on genetic backgrounds which are more highly represented on fragile X chromosomes. These arrays may well be precursors from which the larger fragile X associated arrays have arisen by further expansion.

引用

页码：1553 / 1560

页数：8

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