PMID- 10480360
OWN - NLM
STAT- MEDLINE
DCOM- 19990923
LR  - 20190722
IS  - 0340-6717 (Print)
IS  - 0340-6717 (Linking)
VI  - 105
IP  - 1-2
DP  - 1999 Jul-Aug
TI  - FISH-detected delay in replication timing of mutated FMR1 alleles on both active 
      and inactive X-chromosomes.
PG  - 86-97
AB  - X-chromosome inactivation and the size of the CGG repeat number are assumed to 
      play a role in the clinical, physical, and behavioral phenotype of female 
      carriers of a mutated FMR1 allele. In view of the tight relationship between 
      replication timing and the expression of a given DNA sequence, we have examined 
      the replication timing of FMR1 alleles on active and inactive X-chromosomes in 
      cell samples (lymphocytes or amniocytes) of 25 females: 17 heterozygous for a 
      mutated FMR1 allele with a trinucleotide repeat number varying from 58 to a few 
      hundred, and eight homozygous for a wild-type allele. We have applied two-color 
      fluorescence in situ hybridization (FISH) with FMR1 and X-chromosome 
      alpha-satellite probes to interphase cells of the various genotypes: the 
      alpha-satellite probe was used to distinguish between early replicating (active) 
      and late replicating (inactive) X-chromosomes, and the FMR1 probe revealed the 
      replication pattern of this locus. All samples, except one with a large 
      trinucleotide expansion, showed an early replicating FMR1 allele on the active 
      X-chromosome and a late replicating allele on the inactive X-chromosome. In 
      samples of mutation carriers, both the early and the late alleles showed delayed 
      replication compared with normal alleles, regardless of repeat size. We conclude 
      therefore that: (1) the FMR1 locus is subjected to X-inactivation; (2) mutated 
      FMR1 alleles, regardless of repeat size, replicate later than wild-type alleles 
      on both the active and inactive X-chromosomes; and (3) the delaying effect of the 
      trinucleotide expansion, even with a low repeat size, is superimposed on the 
      delay in replication associated with X-inactivation.
FAU - Yeshaya, J
AU  - Yeshaya J
AD  - Dept. of Human Gentics, Sackler School of Medicine, Tel-Aviv University, Israel.
FAU - Shalgi, R
AU  - Shalgi R
FAU - Shohat, M
AU  - Shohat M
FAU - Avivi, L
AU  - Avivi L
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Hum Genet
JT  - Human genetics
JID - 7613873
RN  - 0 (FMR1 protein, human)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA-Binding Proteins)
RN  - 139135-51-6 (Fragile X Mental Retardation Protein)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - *Alleles
MH  - Amniotic Fluid/cytology
MH  - *DNA Replication
MH  - *Dosage Compensation, Genetic
MH  - Female
MH  - Fragile X Mental Retardation Protein
MH  - Genetic Testing
MH  - Heterozygote
MH  - Humans
MH  - *In Situ Hybridization, Fluorescence
MH  - Lymphocytes/cytology
MH  - Models, Genetic
MH  - *Mutation
MH  - Nerve Tissue Proteins/*genetics
MH  - *RNA-Binding Proteins
MH  - *X Chromosome
EDAT- 1999/09/10 00:00
MHDA- 1999/09/10 00:01
CRDT- 1999/09/10 00:00
PHST- 1999/09/10 00:00 [pubmed]
PHST- 1999/09/10 00:01 [medline]
PHST- 1999/09/10 00:00 [entrez]
AID - 10.1007/s004399900081 [doi]
PST - ppublish
SO  - Hum Genet. 1999 Jul-Aug;105(1-2):86-97. doi: 10.1007/s004399900081.