This gene appears to influence the development in humans of the forebrain. It is also present in mice and xenopus frogs, which suggests a long evolutionary history, and in those organisms its expression is confined to the forebrain, optic and olfactory areas.[4]
VAX1 gene is a transcription factor that has a homeodomain located in the 100-159 amino acid position and an Ala–rich region located in 216-253 amino acid position of the gene. Expression studies in mice show that it is expressed in the palate, coloboma in the visual system, and the basal telencephalon, optic stalk, and visual eye fields where it is expressed along with the Shh and Bmp4 genes.[4][5][6]
Clinical significance
Mice with homozygous VAX1 mutations have been reported to display craniofacial malformations including cleft palate.[7]
Genome Wide Association Studies (GWAS) reported significant associations between non-syndromic clefts and SNPs in the VAX1 gene.[8][9] Replication studies have confirmed these associations in different population groups[10][11]
References
↑Hallonet M, Hollemann T, Wehr R, Jenkins NA, Copeland NG, Pieler T, Gruss P (Aug 1998). "Vax1 is a novel homeobox-containing gene expressed in the developing anterior ventral forebrain". Development. 125 (14): 2599–610. PMID9636075.
↑ 4.04.1Hallonet M, Hollemann T, Wehr R, Jenkins NA, Copeland NG, Pieler T, Gruss P (July 1998). "Vax1 is a novel homeobox-containing gene expressed in the developing anterior ventral forebrain". Development. 125 (14): 2599–610. PMID9636075.
↑Zhao L, Saitsu H, Sun X, Shiota K, Ishibashi M (2010). "Sonic hedgehog is involved in formation of the ventral optic cup by limiting Bmp4 expression to the dorsal domain". Mech. Dev. 127 (1–2): 62–72. doi:10.1016/j.mod.2009.10.006. PMID19854269.
↑Mangold E, Ludwig KU, Birnbaum S, et al. (January 2010). "Genome-wide association study identifies two susceptibility loci for nonsyndromic cleft lip with or without cleft palate". Nat. Genet. 42 (1): 24–6. doi:10.1038/ng.506. PMID20023658.
↑Nikopensius T, Birnbaum S, Ludwig KU, et al. (June 2010). "Susceptibility locus for non-syndromic cleft lip with or without cleft palate on chromosome 10q25 confers risk in Estonian patients". Eur. J. Oral Sci. 118 (3): 317–9. doi:10.1111/j.1600-0722.2010.00741.x. PMID20572868.
↑Rojas-Martinez A, Reutter H, Chacon-Camacho O, et al. (July 2010). "Genetic risk factors for nonsyndromic cleft lip with or without cleft palate in a Mesoamerican population: Evidence for IRF6 and variants at 8q24 and 10q25". Birth Defects Res. Part a Clin. Mol. Teratol. 88 (7): 535–7. doi:10.1002/bdra.20689. PMID20564431.
Deloukas P, Earthrowl ME, Grafham DV, et al. (2004). "The DNA sequence and comparative analysis of human chromosome 10". Nature. 429 (6990): 375–81. doi:10.1038/nature02462. PMID15164054.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID14702039.
