PMID- 19284877
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20110714
LR  - 20211020
IS  - 1755-8166 (Electronic)
IS  - 1755-8166 (Linking)
VI  - 2
DP  - 2009 Mar 14
TI  - Microdeletion syndromes disclose replication timing alterations of genes 
      unrelated to the missing DNA.
PG  - 11
LID - 10.1186/1755-8166-2-11 [doi]
AB  - BACKGROUND: The temporal order of allelic replication is interrelated to the 
      epigenomic profile. A significant epigenetic marker is the asynchronous 
      replication of monoallelically-expressed genes versus the synchronous replication 
      of biallelically-expressed genes. The present study sought to determine whether a 
      microdeletion in the genome affects epigenetic profiles of genes unrelated to the 
      missing segment. In order to test this hypothesis, we checked the replication 
      patterns of two genes - SNRPN, a normally monoallelically expressed gene 
      (assigned to 15q11.13), and the RB1, an archetypic biallelically expressed gene 
      (assigned to 13.q14) in the genomes of patients carrying the 22q11.2 deletion 
      (DiGeorge/Velocardiofacial syndrome) and those carrying the 7q11.23 deletion 
      (Williams syndrome). RESULTS: The allelic replication timing was determined by 
      fluorescence in situ hybridization (FISH) technology performed on peripheral 
      blood cells. As expected, in the cells of normal subjects the frequency of cells 
      showing asynchronous replication for SNRPN was significantly (P < 10-12) higher 
      than the corresponding value for RB1. In contrast, cells of the deletion-carrying 
      patients exhibited a reversal in this replication pattern: there was a 
      significantly lower frequency of cells engaging in asynchronous replication for 
      SNRPN than for RB1 (P < 10-4 and P < 10-3 for DiGeorge/Velocardiofacial and 
      Williams syndromes, respectively). Accordingly, the significantly lower frequency 
      of cells showing asynchronous replication for SNRPN than for RB1 is a new 
      epigenetic marker distinguishing these deletion syndrome genotypes from normal 
      ones. CONCLUSION: In cell samples of each deletion-carrying individual, an 
      aberrant, reversed pattern of replication is delineated, namely, where a 
      monoallelic gene replicates more synchronously than a biallelic gene. This 
      inverted pattern, which appears to be non-deletion-specific, clearly 
      distinguishes cells of deletion-carriers from normal ones. As such, it offers a 
      potential epigenetic marker for suspecting a hidden microdeletion that is too 
      small to be detected by conventional karyotyping methods.
FAU - Yeshaya, Josepha
AU  - Yeshaya J
AD  - Raphael Recanati Genetic Institute, Rabin Medical Center Beilinson Campus, 
      Petah-Tikva, Israel.
FAU - Amir, Itay
AU  - Amir I
AD  - Raphael Recanati Genetic Institute, Rabin Medical Center Beilinson Campus, 
      Petah-Tikva, Israel.
AD  - Department of Human Molecular Genetics & Biochemistry, Sackler School of 
      Medicine, Tel-Aviv University, Tel-Aviv, Israel.
FAU - Rimon, Ayelet
AU  - Rimon A
AD  - Raphael Recanati Genetic Institute, Rabin Medical Center Beilinson Campus, 
      Petah-Tikva, Israel.
FAU - Freedman, Jane
AU  - Freedman J
AD  - Raphael Recanati Genetic Institute, Rabin Medical Center Beilinson Campus, 
      Petah-Tikva, Israel.
FAU - Shohat, Mordechai
AU  - Shohat M
AD  - Raphael Recanati Genetic Institute, Rabin Medical Center Beilinson Campus, 
      Petah-Tikva, Israel.
AD  - Department of Human Molecular Genetics & Biochemistry, Sackler School of 
      Medicine, Tel-Aviv University, Tel-Aviv, Israel.
AD  - Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petah 
      Tikva, Israel.
FAU - Avivi, Lydia
AU  - Avivi L
AD  - Department of Human Molecular Genetics & Biochemistry, Sackler School of 
      Medicine, Tel-Aviv University, Tel-Aviv, Israel.
LA  - eng
PT  - Journal Article
DEP - 20090314
PL  - England
TA  - Mol Cytogenet
JT  - Molecular cytogenetics
JID - 101317942
PMC - PMC2660353
EDAT- 2009/03/17 09:00
MHDA- 2009/03/17 09:01
PMCR- 2009/03/14
CRDT- 2009/03/17 09:00
PHST- 2009/01/02 00:00 [received]
PHST- 2009/03/14 00:00 [accepted]
PHST- 2009/03/17 09:00 [entrez]
PHST- 2009/03/17 09:00 [pubmed]
PHST- 2009/03/17 09:01 [medline]
PHST- 2009/03/14 00:00 [pmc-release]
AID - 1755-8166-2-11 [pii]
AID - 10.1186/1755-8166-2-11 [doi]
PST - epublish
SO  - Mol Cytogenet. 2009 Mar 14;2:11. doi: 10.1186/1755-8166-2-11.