TBX1: Difference between revisions
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==Insights into TBX1== | ==Insights into TBX1== | ||
The gene locus for TBX1 in humans is on 22q11.2 (chromosome 22). This is the region of a common mutation (named 22q11.2 deletion syndrome) characterised by a deletion of 3Mb of DNA (30 genes) leading to the phenotype of the DiGeorge syndrome. By examining patients with DiGeorge syndrome but without the 3Mb deletion syndrome, | The gene locus for TBX1 in humans is on 22q11.2 (chromosome 22). This is the region of a common mutation (named 22q11.2 deletion syndrome) characterised by a deletion of 3Mb of DNA (30 genes) leading to the phenotype of the DiGeorge syndrome. By examining patients with DiGeorge syndrome but without the 3Mb deletion syndrome, <i>tbx1</i> has been flagged as one which has a high mutation rate, and is therefore implicated in DiGeorge syndrome. However, mutations in the protein TBX1 alone do not implicate mental retardation. Mutants of TBX1 are responsible for at least five major phenotypes: | ||
* Conotruncal anomaly face | * Conotruncal anomaly face | ||
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TBX1 has been found to be haploinsufficient, i.e. dosage-specific: mice which carry too few or too many copies of TBX1 typically show most of the signs of DiGeorge syndrome. However, TBX1 may not be the only implicated gene: <i>Crkl</i> mutations causes some of the DiGeorge phenotype abnormalities. | TBX1 has been found to be haploinsufficient, i.e. dosage-specific: mice which carry too few or too many copies of TBX1 typically show most of the signs of DiGeorge syndrome. However, TBX1 may not be the only implicated gene: <i>Crkl</i> mutations causes some of the DiGeorge phenotype abnormalities. | ||
The TBX1 gene consists of twelve exons: 1-8, 9A, 9B, 10 and 9C, and has three alternative spliced forms of the gene. Thus, when screening for mutants the protein must be screened in all three alternative splice forms. One example of such a screening is for the -39 C→T mutation through a technique known as amplification refractory mutation system | The TBX1 gene consists of twelve exons: 1-8, 9A, 9B, 10 and 9C, and has three alternative spliced forms of the gene. Thus, when screening for mutants the protein must be screened in all three alternative splice forms. One example of such a screening is for the -39 C→T mutation through a technique known as ARMS (amplification refractory mutation system). A screening of 38 patients with DiGeorge syndrome without the deletion uncovered this mutant. A functional analysis of this mutation is discussed below. | ||
=Functions and pathways of TBX1= | =Functions and pathways of TBX1= | ||