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Transcriptional Dosage Compensation?
1.200 1.000 0.800 0.600 0.400 0.200 0.000 ‐0.200
Euploid (Donor) Trisomy 15 Monosomy 15
*
*
PPIA (HSK)
MYO9A
FAM189A1
CYFIP1
Genes
• •
•
Why is there no significant gene expression alterations in trisomy 15 embryos? Monosomy embryos have ~half the expression of euploid.
• Due to the missing chromosome
Trisomy embryos DO NOT have 1.5‐fold increase due to the presence of an extra chromosome.
• Transcriptional compensation to accommodate implantation?
Trisomy 21 Transcriptional Compensation
*
McCallie et al, 2016
• Dosage compensation has been reported in studies of Down Syndrome subjects that have shown:
• Tissue specific differences in chromosome 21 genes.
• Many genes displayed the expected 50% increase in transcription. • Others exhibited no differences.
• Some genes had decreased expression.
• A mouse embryonic stem cell line containing single human chromosome 21 revealed differentiating transcriptomic effects on trisomic genes with 53.6% showing primary dosage, 25% dosage compensation and 21.4% reverse dosage effects (Wang et al, 2011).
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Normalized Fold Change