Gene dosage effects of the imprinted delta-like homologue 1 (dlk1/pref1) in development: implications for the evolution of imprinting.
Genomic imprinting is a normal process that causes genes to be expressed according to parental origin. The selective advantage conferred by imprinting is not understood but is hypothesised to act on dosage-critical genes. Here, we report a unique model in which the consequences of a single, double,...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-02-01
|
| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000392&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850183338878304256 |
|---|---|
| author | Simao Teixeira da Rocha Marika Charalambous Shau-Ping Lin Isabel Gutteridge Yoko Ito Dionne Gray Wendy Dean Anne C Ferguson-Smith |
| author_facet | Simao Teixeira da Rocha Marika Charalambous Shau-Ping Lin Isabel Gutteridge Yoko Ito Dionne Gray Wendy Dean Anne C Ferguson-Smith |
| author_sort | Simao Teixeira da Rocha |
| collection | DOAJ |
| description | Genomic imprinting is a normal process that causes genes to be expressed according to parental origin. The selective advantage conferred by imprinting is not understood but is hypothesised to act on dosage-critical genes. Here, we report a unique model in which the consequences of a single, double, and triple dosage of the imprinted Dlk1/Pref1, normally repressed on the maternally inherited chromosome, can be assessed in the growing embryo. BAC-transgenic mice were generated that over-express Dlk1 from endogenous regulators at all sites of embryonic activity. Triple dosage causes lethality associated with major organ abnormalities. Embryos expressing a double dose of Dlk1, recapitulating loss of imprinting, are growth enhanced but fail to thrive in early life, despite the early growth advantage. Thus, any benefit conferred by increased embryonic size is offset by postnatal lethality. We propose a negative correlation between gene dosage and survival that fixes an upper limit on growth promotion by Dlk1, and we hypothesize that trade-off between growth and lethality might have driven imprinting at this locus. |
| format | Article |
| id | doaj-art-1ec664d8d0ac4ffd9cf9bb3a14b211f9 |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2009-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-1ec664d8d0ac4ffd9cf9bb3a14b211f92025-08-20T02:17:24ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042009-02-0152e100039210.1371/journal.pgen.1000392Gene dosage effects of the imprinted delta-like homologue 1 (dlk1/pref1) in development: implications for the evolution of imprinting.Simao Teixeira da RochaMarika CharalambousShau-Ping LinIsabel GutteridgeYoko ItoDionne GrayWendy DeanAnne C Ferguson-SmithGenomic imprinting is a normal process that causes genes to be expressed according to parental origin. The selective advantage conferred by imprinting is not understood but is hypothesised to act on dosage-critical genes. Here, we report a unique model in which the consequences of a single, double, and triple dosage of the imprinted Dlk1/Pref1, normally repressed on the maternally inherited chromosome, can be assessed in the growing embryo. BAC-transgenic mice were generated that over-express Dlk1 from endogenous regulators at all sites of embryonic activity. Triple dosage causes lethality associated with major organ abnormalities. Embryos expressing a double dose of Dlk1, recapitulating loss of imprinting, are growth enhanced but fail to thrive in early life, despite the early growth advantage. Thus, any benefit conferred by increased embryonic size is offset by postnatal lethality. We propose a negative correlation between gene dosage and survival that fixes an upper limit on growth promotion by Dlk1, and we hypothesize that trade-off between growth and lethality might have driven imprinting at this locus.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000392&type=printable |
| spellingShingle | Simao Teixeira da Rocha Marika Charalambous Shau-Ping Lin Isabel Gutteridge Yoko Ito Dionne Gray Wendy Dean Anne C Ferguson-Smith Gene dosage effects of the imprinted delta-like homologue 1 (dlk1/pref1) in development: implications for the evolution of imprinting. PLoS Genetics |
| title | Gene dosage effects of the imprinted delta-like homologue 1 (dlk1/pref1) in development: implications for the evolution of imprinting. |
| title_full | Gene dosage effects of the imprinted delta-like homologue 1 (dlk1/pref1) in development: implications for the evolution of imprinting. |
| title_fullStr | Gene dosage effects of the imprinted delta-like homologue 1 (dlk1/pref1) in development: implications for the evolution of imprinting. |
| title_full_unstemmed | Gene dosage effects of the imprinted delta-like homologue 1 (dlk1/pref1) in development: implications for the evolution of imprinting. |
| title_short | Gene dosage effects of the imprinted delta-like homologue 1 (dlk1/pref1) in development: implications for the evolution of imprinting. |
| title_sort | gene dosage effects of the imprinted delta like homologue 1 dlk1 pref1 in development implications for the evolution of imprinting |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000392&type=printable |
| work_keys_str_mv | AT simaoteixeiradarocha genedosageeffectsoftheimprinteddeltalikehomologue1dlk1pref1indevelopmentimplicationsfortheevolutionofimprinting AT marikacharalambous genedosageeffectsoftheimprinteddeltalikehomologue1dlk1pref1indevelopmentimplicationsfortheevolutionofimprinting AT shaupinglin genedosageeffectsoftheimprinteddeltalikehomologue1dlk1pref1indevelopmentimplicationsfortheevolutionofimprinting AT isabelgutteridge genedosageeffectsoftheimprinteddeltalikehomologue1dlk1pref1indevelopmentimplicationsfortheevolutionofimprinting AT yokoito genedosageeffectsoftheimprinteddeltalikehomologue1dlk1pref1indevelopmentimplicationsfortheevolutionofimprinting AT dionnegray genedosageeffectsoftheimprinteddeltalikehomologue1dlk1pref1indevelopmentimplicationsfortheevolutionofimprinting AT wendydean genedosageeffectsoftheimprinteddeltalikehomologue1dlk1pref1indevelopmentimplicationsfortheevolutionofimprinting AT annecfergusonsmith genedosageeffectsoftheimprinteddeltalikehomologue1dlk1pref1indevelopmentimplicationsfortheevolutionofimprinting |