PUBLICATION
Evolutionarily assembled cis-regulatory module at a human ciliopathy locus
- Authors
- Lee, J.H., Silhavy, J.L., Lee, J.E., Al-Gazali, L., Thomas, S., Davis, E.E., Bielas, S.L., Hill, K.J., Iannicelli, M., Brancati, F., Gabriel, S.B., Russ, C., Logan, C.V., Sharif, S.M., Bennett, C.P., Abe, M., Hildebrandt, F., Diplas, B.H., Attié-Bitach, T., Katsanis, N., Rajab, A., Koul, R., Sztriha, L., Waters, E.R., Ferro-Novick, S., Woods, C.G., Johnson, C.A., Valente, E.M., Zaki, M.S., Gleeson, J.G.
- ID
- ZDB-PUB-200522-20
- Date
- 2012
- Source
- Science (New York, N.Y.) 335: 966-9 (Journal)
- Registered Authors
- Davis, Erica, Hildebrandt, Friedhelm, Katsanis, Nicholas, Lee, Ji Eun
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Cell Line
- Cerebellar Diseases/genetics*
- Cerebellar Diseases/metabolism
- Cerebellar Diseases/pathology
- Cilia/metabolism
- Cilia/ultrastructure*
- Conserved Sequence
- DNA, Intergenic
- Evolution, Molecular*
- Eye Abnormalities/genetics*
- Eye Abnormalities/metabolism
- Eye Abnormalities/pathology
- Gene Expression Profiling
- Gene Expression Regulation*
- Genetic Heterogeneity
- Genetic Loci*
- Humans
- Kidney Diseases, Cystic/genetics*
- Kidney Diseases, Cystic/metabolism
- Kidney Diseases, Cystic/pathology
- Membrane Proteins/chemistry
- Membrane Proteins/genetics*
- Membrane Proteins/metabolism
- Molecular Sequence Data
- Multigene Family
- Mutation
- Mutation, Missense
- Phenotype
- Protein Transport
- Regulatory Sequences, Nucleic Acid*
- Retina/abnormalities
- Retina/metabolism
- Retina/pathology
- Transport Vesicles/metabolism
- Transport Vesicles/ultrastructure
- PubMed
- 22282472 Full text @ Science
Citation
Lee, J.H., Silhavy, J.L., Lee, J.E., Al-Gazali, L., Thomas, S., Davis, E.E., Bielas, S.L., Hill, K.J., Iannicelli, M., Brancati, F., Gabriel, S.B., Russ, C., Logan, C.V., Sharif, S.M., Bennett, C.P., Abe, M., Hildebrandt, F., Diplas, B.H., Attié-Bitach, T., Katsanis, N., Rajab, A., Koul, R., Sztriha, L., Waters, E.R., Ferro-Novick, S., Woods, C.G., Johnson, C.A., Valente, E.M., Zaki, M.S., Gleeson, J.G. (2012) Evolutionarily assembled cis-regulatory module at a human ciliopathy locus. Science (New York, N.Y.). 335:966-9.
Abstract
Neighboring genes are often coordinately expressed within cis-regulatory modules, but evidence that nonparalogous genes share functions in mammals is lacking. Here, we report that mutation of either TMEM138 or TMEM216 causes a phenotypically indistinguishable human ciliopathy, Joubert syndrome. Despite a lack of sequence homology, the genes are aligned in a head-to-tail configuration and joined by chromosomal rearrangement at the amphibian-to-reptile evolutionary transition. Expression of the two genes is mediated by a conserved regulatory element in the noncoding intergenic region. Coordinated expression is important for their interdependent cellular role in vesicular transport to primary cilia. Hence, during vertebrate evolution of genes involved in ciliogenesis, nonparalogous genes were arranged to a functional gene cluster with shared regulatory elements.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping