X INACTIVATION OF THE FMR1 FRAGILE-X MENTAL-RETARDATION GENE

被引:32
作者
KIRCHGESSNER, CU
WARREN, ST
WILLARD, HF
机构
[1] CASE WESTERN RESERVE UNIV,SCH MED,CTR HUMAN GENET,DEPT GENET,CLEVELAND,OH 44106
[2] STANFORD UNIV,SCH MED,DEPT GENET,STANFORD,CA 94305
[3] EMORY UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT BIOCHEM,ATLANTA,GA 30322
[4] EMORY UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT PEDIAT,ATLANTA,GA 30322
关键词
D O I
10.1136/jmg.32.12.925
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
X chromosome inactivation has been hypothesised to play a role in the aetiology and clinical expression of the fragile X syndrome. The identification of the FMR1 gene involved in fragile X syndrome allows testing of the assumption that the fragile X locus is normally subject to X inactivation. We studied the expression of the FMR1 gene from inactive X chromosomes by reverse transcription of RNA followed by PCR (RT-PCR), both in somatic cell hybrids which retain an active or inactive human X chromosome and in a female patient with a large deletion surrounding the FMR1 gene. In both analyses, the data indicate that FMR1 is not normally expressed from the inactive X chromosome and is, therefore, subject to X chromosome inactivation. This finding is consistent with the results of previous studies of DNA methylation of FMR1 on active and inactive X chromosomes, verifies previous assumptions about the fragile X locus, and supports the involvement of X inactivation in the variable phenotype of females with full mutations of the FMR1 gene.
引用
收藏
页码:925 / 929
页数:5
相关论文
共 35 条
[1]   HUMAN AND MURINE FMR-1 - ALTERNATIVE SPLICING AND TRANSLATIONAL INITIATION DOWNSTREAM OF THE CGG-REPEAT [J].
ASHLEY, CT ;
SUTCLIFFE, JS ;
KUNST, CB ;
LEINER, HA ;
EICHLER, EE ;
NELSON, DL ;
WARREN, ST .
NATURE GENETICS, 1993, 4 (03) :244-251
[2]   X-CHROMOSOME INACTIVATION OF THE HUMAN TIMP GENE [J].
BROWN, CJ ;
FLENNIKEN, AM ;
WILLIAMS, BRG ;
WILLARD, HF .
NUCLEIC ACIDS RESEARCH, 1990, 18 (14) :4191-4195
[3]  
BROWN CJ, 1994, NATURE, V368, P646
[4]   DIFFERENTIAL METHYLATION OF THE HYPERVARIABLE LOCUS DXS255 ON ACTIVE AND INACTIVE X-CHROMOSOMES CORRELATES WITH THE EXPRESSION OF A HUMAN X-LINKED GENE [J].
BROWN, RM ;
FRASER, NJ ;
BROWN, GK .
GENOMICS, 1990, 7 (02) :215-221
[5]  
CLARKE JTR, 1990, CLIN GENET, V37, P355
[6]  
CLARKE JTR, 1991, AM J HUM GENET, V49, P289
[7]  
CLARKE JTR, 1992, AM J HUM GENET, V51, P316
[8]   HURLERS SYNDROME - A GENETIC STUDY OF CLONES IN CELL CULTURE WITH PARTICULAR REFERENCE TO LYON HYPOTHESIS [J].
DANES, BS ;
BEARN, AG .
JOURNAL OF EXPERIMENTAL MEDICINE, 1967, 126 (03) :509-&
[9]   ESCAPE FROM X-INACTIVATION IN HUMAN AND MOUSE [J].
DISTECHE, CM .
TRENDS IN GENETICS, 1995, 11 (01) :17-22
[10]   VARIATION OF THE CGG REPEAT AT THE FRAGILE-X SITE RESULTS IN GENETIC INSTABILITY - RESOLUTION OF THE SHERMAN PARADOX [J].
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 .
CELL, 1991, 67 (06) :1047-1058