TCOF1

Gene

The TCOF1 gene is located on the long (q) arm of chromosome 5 between positions 32 and 33.1, from base pair 150,357,629 to base pair 150,400,308.

Function

TCOF1 is involved in the production of a molecule called ribosomal RNA (rRNA) within cells. TCOF1 is active in the nucleolus, which is a small region inside the nucleus where rRNA is produced. As a major component of cell structures called ribosomes, rRNA is essential for the assembly of proteins. This protein is active during early embryonic development in structures that become bones and other tissues in the face. Although the precise function of this protein is unknown, researchers believe that it plays a critical role in the development of facial bones and related structures.

Aside from its interaction with UBF, treacle has been implicated in the methylation of the precursor to mature ribosomal RNA by interaction with the nucleolar protein pNop56.

Clinical significance

More than 120 mutations in the TCOF1 gene have been identified in people with Treacher Collins syndrome. Most of these mutations insert or delete a small number of DNA building blocks (base pairs) in the TCOF1 gene. TCOF1 mutations lead to the production of an abnormally small, nonfunctional version of treacle or prevent the cell from producing this protein. Researchers speculate that a loss of treacle reduces the production of rRNA in parts of the embryo that develop into facial bones and tissues. It is not known how loss of the treacle protein causes the specific problems with facial development found in Treacher Collins syndrome. For instance, mutations in the TCOF gene of these individuals often result in a cleft palate.

Model organisms

Mutations in this gene in Jindo dogs have been associated to the observed cranial differences between Jindo and boxer dogs.

References

References

1. (September 1991). "Mapping the Treacher Collins syndrome locus to 5q31.3----q33.3". Genomics.
2. "Entrez Gene: TCOF1 Treacher Collins-Franceschetti syndrome 1".
3. (July 2004). "The Treacher Collins syndrome (TCOF1) gene product is involved in ribosomal DNA gene transcription by interacting with upstream binding factor". Proceedings of the National Academy of Sciences of the United States of America.
4. "Chromosome 5: 150,357,629-150,400,308 - Region in detail - Homo_sapiens - Ensembl genome browser 113".
5. (April 1997). "TCOF1 gene encodes a putative nucleolar phosphoprotein that exhibits mutations in Treacher Collins Syndrome throughout its coding region". Proceedings of the National Academy of Sciences of the United States of America.
6. "Ribosomes, Transcription, Translation {{!}} Learn Science at Scitable".
7. "TCOF1 gene: MedlinePlus Genetics".
8. (September 2006). "Tcof1/Treacle is required for neural crest cell formation and proliferation deficiencies that cause craniofacial abnormalities". Proceedings of the National Academy of Sciences of the United States of America.
9. (July 2005). "The Treacher Collins syndrome (TCOF1) gene product is involved in pre-rRNA methylation". Human Molecular Genetics.
10. (March 2011). "Cleft lip and palate: understanding genetic and environmental influences". Nature Reviews. Genetics.
11. (June 2012). "Genome analysis of the domestic dog (Korean Jindo) by massively parallel sequencing". DNA Research.