DNA-REPLICATION ASYNCHRONY BETWEEN THE PATERNAL AND MATERNAL ALLELES OF IMPRINTED GENES DOES NOT STRADDLE THE R G TRANSITION/

Imprinted autosomal loci apparently reside in very large chromosomal d omains that exhibit asynchrony in replication of homologous alleles du ring the DNA synthesis phase. Replication asynchrony can be cytogeneti cally visualized by a replication-banding discordance between homologo us bands of a given pair of chromosomal homologs. The replication time of a chromosomal band at high resolution can be determined by blockin g DNA synthesis at the R/G-band transition and using replication bandi ng. The R/G transition reflects the transition from early (R-) to late (G- and C-) band DNA replication. We studied discordance between two groups of homologous chromosomal bands: (a) four bands, 6q26-27, 11p13 , 11p15.5 and 15q11.2-12, each containing at least one imprinted gene; and (b) nine bands containing no known imprinted genes. Fifty pairs o f chromosomes were analyzed at high resolution after R/G transition bl ocking and late 5-bromo-2'-deoxyuridine incorporation. The rate of dis cordance was the same for bands containing imprinted genes and for con trol bands. Both homologous bands of a pair replicate either before or after the R/G transition and do not straddle the R/G transition. Repr ession associated with imprinting does not appear to involve late repl ication at the band level of resolution. Tissue-specific inactivation is associated with DNA methylation and late replication, whereas allel e-specific inactivation is associated with DNA methylation but not wit h delayed or late replication.