FISH-detected delay in replication timing of mutated FMR1 alleles on both active and inactive X-chromosomes.

摘要: X-chromosome inactivation and the size of CGG repeat number are assumed to play a role in clinical, physical, behavioral phenotype female carriers mutated FMR1 allele. In view tight relationship between replication timing expression given DNA sequence, we have examined alleles on active inactive X-chromosomes cell samples (lymphocytes or amniocytes) 25 females: 17 heterozygous for allele with trinucleotide varying from 58 few hundred, eight homozygous wild-type We applied two-color fluorescence situ hybridization (FISH) α-satellite probes interphase cells various genotypes: probe was used distinguish early replicating (active) late (inactive) X-chromosomes, revealed pattern this locus. All samples, except one large expansion, showed an X-chromosome. mutation carriers, both delayed compared normal alleles, regardless size. conclude therefore that: (1) locus is subjected X-inactivation; (2) size, replicate later than X-chromosomes; (3) delaying effect even low superimposed delay associated X-inactivation.