PMID- 29750268
OWN - NLM
STAT- MEDLINE
DCOM- 20190730
LR  - 20190730
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 46
IP  - 14
DP  - 2018 Aug 21
TI  - Inferring and modeling inheritance of differentially methylated changes across 
      multiple generations.
PG  - e85
LID - 10.1093/nar/gky362 [doi]
AB  - High-throughput methylation sequencing enables genome-wide detection of 
      differentially methylated sites (DMS) or regions (DMR). Increasing evidence 
      suggests that treatment-induced DMS can be transmitted across generations, but 
      the analysis of induced methylation changes across multiple generations is 
      complicated by the lack of sound statistical methods to evaluate significance 
      levels. Due to software design, DMS detection was usually made on each generation 
      separately, thus disregarding stochastic effects expected when a large number of 
      DMS is detected in each generation. Here, we present a novel method based on 
      Monte Carlo sampling, methylInheritance, to evaluate that the number of conserved 
      DMS between several generations is associated to an effect inherited from a 
      treatment and not randomness. Moreover, we developed an inheritance simulation 
      package, methInheritSim, to demonstrate the performance of the methylInheritance 
      method and to evaluate the power of different experimental designs. Finally, we 
      applied methylInheritance to a DNA methylation dataset obtained from early-life 
      persistent organic pollutants (POPs) exposed Sprague-Dawley female rats and their 
      descendants through a paternal transmission. The results show that 
      metylInheritance can efficiently identify treatment-induced inherited methylation 
      changes. Specifically, we identified two intergenerationally conserved DMS at 
      transcription start site (TSS); one of those persisted transgenerationally. Three 
      transgenerationally conserved DMR were found at intra or integenic regions.
FAU - Belleau, Pascal
AU  - Belleau P
AD  - Departement de Medecine Moleculaire - Universite Laval, Faculte de medecine, 
      Pavillon Ferdinand-Vandry, 1050 avenue de la Medecine, bureau 4633, Quebec, QC 
      G1V 0A6, Canada.
FAU - Deschenes, Astrid
AU  - Deschenes A
AD  - Centre de Recherche du CHU de Quebec - Universite Laval, 2705 boulevard Laurier, 
      Quebec, QC G1V 4G2, Canada.
FAU - Scott-Boyer, Marie-Pier
AU  - Scott-Boyer MP
AD  - Centre de Recherche du CHU de Quebec - Universite Laval, 2705 boulevard Laurier, 
      Quebec, QC G1V 4G2, Canada.
FAU - Lambrot, Romain
AU  - Lambrot R
AD  - Department of Animal Sciences, McGill University, Ste. Anne de Bellevue, Quebec, 
      H9 x 3V9 Canada and Department of Pharmacology and Therapeutics, McGill 
      University, Montreal, Quebec H3G 1Y6, Canada.
FAU - Dalvai, Mathieu
AU  - Dalvai M
AD  - Centre de recherche en reproduction, developpement et sante intergenerationnelle 
      - Universite Laval, Faculte des sciences de l'agriculture et de l'alimentation, 
      Pavillon Paul-Comtois, 2425 rue de l'Agriculture, Quebec, QC G1V 0A6, Canada.
FAU - Kimmins, Sarah
AU  - Kimmins S
AD  - Department of Animal Sciences, McGill University, Ste. Anne de Bellevue, Quebec, 
      H9 x 3V9 Canada and Department of Pharmacology and Therapeutics, McGill 
      University, Montreal, Quebec H3G 1Y6, Canada.
FAU - Bailey, Janice
AU  - Bailey J
AD  - Centre de recherche en reproduction, developpement et sante intergenerationnelle 
      - Universite Laval, Faculte des sciences de l'agriculture et de l'alimentation, 
      Pavillon Paul-Comtois, 2425 rue de l'Agriculture, Quebec, QC G1V 0A6, Canada.
FAU - Droit, Arnaud
AU  - Droit A
AD  - Departement de Medecine Moleculaire - Universite Laval, Faculte de medecine, 
      Pavillon Ferdinand-Vandry, 1050 avenue de la Medecine, bureau 4633, Quebec, QC 
      G1V 0A6, Canada.
AD  - Centre de Recherche du CHU de Quebec - Universite Laval, 2705 boulevard Laurier, 
      Quebec, QC G1V 4G2, Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (Environmental Pollutants)
EIN - Nucleic Acids Res. 2018 Aug 21;46(14):7466. PMID: 29788315
MH  - Animals
MH  - Computer Simulation
MH  - *DNA Methylation
MH  - Environmental Pollutants
MH  - Epigenesis, Genetic
MH  - Female
MH  - *Inheritance Patterns
MH  - Male
MH  - Models, Genetic
MH  - Monte Carlo Method
MH  - Rats, Sprague-Dawley
PMC - PMC6101575
EDAT- 2018/05/12 06:00
MHDA- 2019/07/31 06:00
PMCR- 2018/05/10
CRDT- 2018/05/12 06:00
PHST- 2018/01/18 00:00 [received]
PHST- 2018/04/24 00:00 [accepted]
PHST- 2018/05/12 06:00 [pubmed]
PHST- 2019/07/31 06:00 [medline]
PHST- 2018/05/12 06:00 [entrez]
PHST- 2018/05/10 00:00 [pmc-release]
AID - 4994677 [pii]
AID - gky362 [pii]
AID - 10.1093/nar/gky362 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2018 Aug 21;46(14):e85. doi: 10.1093/nar/gky362.