EDAR and other genes provide instructions for making proteins that work together during embryonic development. These proteins form part of a signaling pathway that is critical for the interaction between two cell layers, the ectoderm and the mesoderm. In the early embryo, these cell layers form the basis for many of the body's organs and tissues. Ectoderm-mesoderm interactions are essential for the proper formation of several structures that arise from the ectoderm, including the skin, hair, nails, teeth, and sweat glands.
A point mutation in EDAR, 370A, found in most East Asians but not common in African or European populations, is thought to be responsible for a number of differences between these populations, including the thicker hair, more numerous sweat glands, smaller breasts, and dentition characteristic of East Asians. The difference in dentition was not visible in mice due to the radically different structure of mice from human teeth, but it is considered reasonable that that difference also is due to the mutation. The 370A mutation arose in humans approximately 30,000 years ago, and now is found in 93% of Han Chinese and in the majority of people in nearby Asian populations.
^Kamberov YG, Wang S, Tan J, Gerbault P, Wark A, Tan L, Yang Y, Li S, Tang K, Chen H, Powell A, Itan Y, Fuller D, Lohmueller J Mao J, Schachar A, Paymer M, Hostetter E, Byrne E, Burnett M, McMahon AP, Thomas MG, Lieberman EE, Jin L, Tabin CJ, Morgan BA, Sabeti PC (2013). "Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant". Cell152 (4): 691–702. doi:10.1016/j.cell.2013.01.016.
Ho L, Williams MS, Spritz RA (1998). "A gene for autosomal dominant hypohidrotic ectodermal dysplasia (EDA3) maps to chromosome 2q11-q13". Am. J. Hum. Genet.62 (5): 1102–6. doi:10.1086/301839. PMC1377096. PMID9545409.
Kumar A, Eby MT, Sinha S, et al. (2001). "The ectodermal dysplasia receptor activates the nuclear factor-kappaB, JNK, and cell death pathways and binds to ectodysplasin A". J. Biol. Chem.276 (4): 2668–77. doi:10.1074/jbc.M008356200. PMID11035039.
Yan M, Wang LC, Hymowitz SG, et al. (2000). "Two-amino acid molecular switch in an epithelial morphogen that regulates binding to two distinct receptors". Science290 (5491): 523–7. doi:10.1126/science.290.5491.523. PMID11039935.
Elomaa O, Pulkkinen K, Hannelius U, et al. (2001). "Ectodysplasin is released by proteolytic shedding and binds to the EDAR protein". Hum. Mol. Genet.10 (9): 953–62. doi:10.1093/hmg/10.9.953. PMID11309369.
Koppinen P, Pispa J, Laurikkala J, et al. (2001). "Signaling and subcellular localization of the TNF receptor Edar". Exp. Cell Res.269 (2): 180–92. doi:10.1006/excr.2001.5331. PMID11570810.
Headon DJ, Emmal SA, Ferguson BM, et al. (2002). "Gene defect in ectodermal dysplasia implicates a death domain adapter in development". Nature414 (6866): 913–6. doi:10.1038/414913a. PMID11780064.
Yan M, Zhang Z, Brady JR, et al. (2002). "Identification of a novel death domain-containing adaptor molecule for ectodysplasin-A receptor that is mutated in crinkled mice". Curr. Biol.12 (5): 409–13. doi:10.1016/S0960-9822(02)00687-5. PMID11882293.
Sinha SK, Zachariah S, Quiñones HI, et al. (2003). "Role of TRAF3 and -6 in the activation of the NF-kappa B and JNK pathways by X-linked ectodermal dysplasia receptor". J. Biol. Chem.277 (47): 44953–61. doi:10.1074/jbc.M207923200. PMID12270937.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A.99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC139241. PMID12477932.
Shu H, Chen S, Bi Q, et al. (2004). "Identification of phosphoproteins and their phosphorylation sites in the WEHI-231 B lymphoma cell line". Mol. Cell Proteomics3 (3): 279–86. doi:10.1074/mcp.D300003-MCP200. PMID14729942.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res.14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC528928. PMID15489334.
Chassaing N, Bourthoumieu S, Cossee M, et al. (2006). "Mutations in EDAR account for one-quarter of non-ED1-related hypohidrotic ectodermal dysplasia". Hum. Mutat.27 (3): 255–9. doi:10.1002/humu.20295. PMID16435307.
Tariq M, Wasif N, Ahmad W (2007). "A novel deletion mutation in the EDAR gene in a Pakistani family with autosomal recessive hypohidrotic ectodermal dysplasia". Br. J. Dermatol.157 (1): 207–9. doi:10.1111/j.1365-2133.2007.07949.x. PMID17501952.