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| Status |
Public on Oct 31, 2017 |
| Title |
Global misregulation of genes largely uncoupled to DNA methylome epimutations characterizes a congenital overgrowth syndrome |
| Organism |
Bos indicus x Bos taurus |
| Experiment type |
Methylation profiling by high throughput sequencing
|
| Summary |
Assisted reproductive therapies (ART) have become increasingly common worldwide and up to ~6% of children currently born in developed countries were conceived employing these technologies. Numerous retrospective studies have suggested that ART-conceived children are more likely to develop the overgrowth syndrome Beckwith-Wiedemann (BWS). In bovine, the use of ART can induce a similar overgrown condition, which is referred to as large offspring syndrome (LOS). Both BWS and LOS involve dysregulation of imprinted genes. However, it remains largely unknown whether aberrant gene expression and DNA methylation occur at non-imprinted loci and to what extent these molecular alterations can contribute to these syndromes. Here we examined the transcriptome of skeletal muscle, liver, kidney, and brain of control and LOS bovine fetuses and found that different LOS fetuses exhibit different severity of the transcriptome alterations and different tissues have distinct gene pathways disturbed in LOS fetuses. Particularly for skeletal muscle, multiple pathways involved in myoblast proliferation and fusion into myotubes are misregulated in LOS fetuses. Further, characterization of the methylome of skeletal muscle demonstrates numerous local methylation differences; however, global DNA methylation is comparable between all individuals regardless of bodyweight. Importantly, only a small percent of differentially expressed genes (DEGs) including the imprinted gene IGF2R can be linked to the neighboring differentially methylated regions (DMRs). In summary, we not only show that misregulation of non-imprinted genes in addition to loss-of-imprinting contributes to the ART-induced overgrowth syndrome but also demonstrate that most of the aberrant gene expression is not associated with DNA methylome epimutations.
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| Overall design |
Comparison of DNA methylome of fetal skeletal muscle between control and overgrown bovine fetuses; Comparison of transcriptome of skeletal muscle, brain, kidney, and liver of control and overgrown bovine fetuses
This Series represents the DNA methylome dataset. The RNA-seq data of brain, kidney, liver, and skeletal muscle have been deposited in GEO database under accession number: GSE63509.
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| Contributor(s) |
Chen Z, Hagen DE, Ji T, Elsik CG, Rivera RM |
| Citation(s) |
28978943 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R21 HD062920 |
Establishment of a phenotypical model of adverse outcomes associated with ART |
UNIVERSITY OF MISSOURI-COLUMBIA |
Rocio Melissa Rivera |
|
| Submission date |
Jan 18, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Rocío Melissa Rivera |
| E-mail(s) |
riverarm@missouri.edu
|
| Organization name |
University of Missouri, Columbia
|
| Department |
Animal Sciences
|
| Street address |
920 East Campus Drive, ASRC 164
|
| City |
Columbia |
| State/province |
MO |
| ZIP/Postal code |
65211 |
| Country |
USA |
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| Platforms (2) |
| GPL22942 |
Illumina HiSeq 2000 (Bos taurus indicus x Bos taurus taurus) |
| GPL22943 |
Illumina HiSeq 2500 (Bos taurus indicus x Bos taurus taurus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA362345 |
| SRA |
SRP096970 |
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