Ectodysplasin A receptor

"EDAR" redirects here. For other uses, see EDAR (disambiguation).

Ectodysplasin A receptor (EDAR) is a protein that in humans is encoded by the EDAR gene. EDAR is a cell surface receptor for ectodysplasin A which plays an important role in the development of ectodermal tissues such as the skin.[1][2][3] It is structurally related to members of the TNF receptor superfamily.[4]

Function

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.[3]

Clinical significance

Mutation in this gene have been associated with hypohidrotic ectodermal dysplasia, a disorder characterized by a lower density of sweat glands.[3]

Derived EDAR allele

A derived G-allele point mutation (SNP) with pleiotropic effects in EDAR, 370A or rs3827760, found in ancient and modern East Asians, Southeast Asians, Nepalese[5] and Native Americans but not common in African or European populations. Experimental research in mice has linked the derived allele to a number of traits, including greater hair shaft diameter, more numerous sweat glands, smaller mammary fat pad, and increased mammary gland density.[6]

A 2008 study stated that EDAR is a genetic determinant for hair thickness, and also contributed to variations in hair thickness among Asian populations.[7]

A 2013 study suggested that the EDAR variant (370A) arose about 35,000 years ago in central China, period during which the region was then quite warm and humid.[8] A subsequent study from 2021, based on ancient DNA samples, has suggested that the derived variant became dominant among "Ancient Northern East Asians" shortly after the Last Glacial Maximum in Northeast Asia, around 19,000 years ago. Ancient remains from Northern East Asia, such as the Tianyuan Man (40,000 years old) and the AR33K (33,000 years old) specimen lacked the derived EDAR allele, while ancient East Asian remains after the LGM carry the derived EDAR allele.[9][10] The frequency of 370A is most highly elevated in North Asian and East Asian populations.[11] In a study of 222 Korean and 265 Japanese subjects, the 370A mutation was found in 86.9% Korean (Busan) and 77.5% Japanese (Tokyo) subjects.[12] This mutation is also implicated in ear morphology differences and reduced chin protrusion.[13]

It has been hypothesized that natural selection favored this allele during the last ice age in a population of people living in isolation in Beringia, as it may play a role in the synthesis of Vitamin D-rich breast milk in dark environments.[14][15][16] One study suggested that because the EDAR mutation arose in a cool and dry environment, it may have been adaptive by increasing skin lubrication, thus reducing dryness in exposed facial structures.[17]

The derived G-allele is a variation of the A-allele in earlier hominids, the version found in most modern non-East Asian and non-Native American populations and is found in 100% of Native American skeletal remains within all Native American haplogroups which studies have been done on prior to all contact from foreign population from Africa, Europe, or Asia. The derived allele was present in both the Tibeto-Burman (Magar and Newar) and Indo-European (Brahmin) populations of Nepal. The highest 1540C allele frequency was observed in Magar (71%), followed by Newar (30%) and Brahmin (20%).[5]

Derived variants of EDAR are associated with multiple facial and dental characteristics, such as shovel-shaped incisors.[18][19] [20][21]

50% of ancient DNA samples (7,900-7,500 BP) from Motala, Sweden; two (3300–3000 BC) from the Afanasevo culture and one (400–200 BC) Scythian sample were found to carry the rs3827760 mutation.[22]

According to a 2018 study, several ancient DNA samples from the Americas, including USR1 from the Upward Sun River site, Anzick-1, and the 9,600 BP individual from Lapa do Santo, were found to not carry the derived allele. This suggests that the increased frequency of the derived allele occurred independently in both East Asia and the Americas.[23]

A 2021 study analyzed the DNA of 6 Jomon remains from Japan and found that none of them carried the derived EDAR allele that is fixed in modern East Asian populations.[24]

See also

References

  1. ^ Monreal AW, Ferguson BM, Headon DJ, Street SL, Overbeek PA, Zonana J (August 1999). "Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia". Nature Genetics. 22 (4): 366–9. doi:10.1038/11937. PMID 10431241. S2CID 11348633.
  2. ^ Aswegan AL, Josephson KD, Mowbray R, Pauli RM, Spritz RA, Williams MS (November 1997). "Autosomal dominant hypohidrotic ectodermal dysplasia in a large family". American Journal of Medical Genetics. 72 (4): 462–7. doi:10.1002/(SICI)1096-8628(19971112)72:4<462::AID-AJMG17>3.0.CO;2-P. PMID 9375732.
  3. ^ a b c "Entrez Gene: EDAR ectodysplasin A receptor".
  4. ^ Online Mendelian Inheritance in Man (OMIM): 604095
  5. ^ a b Basnet, Rajdip; Rai, Niraj; Tamang, Rakesh; Awasthi, Nagendra Prasad; Pradhan, Isha; Parajuli, Pawan; Kashyap, Deepak; Reddy, Alla Govardhan; Chaubey, Gyaneshwer; Das Manandhar, Krishna; Shrestha, Tilak Ram; Thangaraj, Kumarasamy (2022-10-15). "The matrilineal ancestry of Nepali populations". Human Genetics. 142 (2): 167–180. doi:10.1007/s00439-022-02488-z. ISSN 0340-6717. PMID 36242641. S2CID 252904281.
  6. ^ Kamberov YG, Wang S, Tan J, Gerbault P, Wark A, Tan L, et al. (February 2013). "Modeling recent human evolution in mice by expression of a selected EDAR variant". Cell. 152 (4): 691–702. doi:10.1016/j.cell.2013.01.016. PMC 3575602. PMID 23415220.
  7. ^ Fujimoto, Akihiro; Ohashi, Jun; Nishida, Nao; et al. (2008). "A replication study confirmed the EDAR gene to be a major contributor to population differentiation regarding head hair thickness in Asia". Human Genetics. 124 (2): 179–185 – via NCBI.
  8. ^ "EDAR gene: MedlinePlus Genetics". medlineplus.gov. Retrieved 2021-10-18.
  9. ^ Mao, Xiaowei; Zhang, Hucai; Qiao, Shiyu; Liu, Yichen; Chang, Fengqin; Xie, Ping; Zhang, Ming; Wang, Tianyi; Li, Mian; Cao, Peng; Yang, Ruowei; Liu, Feng; Dai, Qingyan; Feng, Xiaotian; Ping, Wanjing (2021-06-10). "The deep population history of northern East Asia from the Late Pleistocene to the Holocene". Cell. 184 (12): 3256–3266.e13. doi:10.1016/j.cell.2021.04.040. ISSN 0092-8674. PMID 34048699.
  10. ^ Zhang, Xiaoming; Ji, Xueping; Li, Chunmei; Yang, Tingyu; Huang, Jiahui; Zhao, Yinhui; Wu, Yun; Ma, Shiwu; Pang, Yuhong; Huang, Yanyi; He, Yaoxi; Su, Bing (25 July 2022). "A Late Pleistocene human genome from Southwest China". Current Biology. 32 (14): 3095–3109.e5. Bibcode:2022CBio...32E3095Z. doi:10.1016/j.cub.2022.06.016. ISSN 0960-9822. PMID 35839766. S2CID 250502011.
  11. ^ Hlusko, Leslea J.; Carlson, Joshua P.; Chaplin, George; Elias, Scott A.; Hoffecker, John F.; Huffman, Michaela; Jablonski, Nina G.; Monson, Tesla A.; O’Rourke, Dennis H.; Pilloud, Marin A.; Scott, G. Richard (2018-05-08). "Environmental selection during the last ice age on the mother-to-infant transmission of vitamin D and fatty acids through breast milk". Proceedings of the National Academy of Sciences. 115 (19): E4426–E4432. Bibcode:2018PNAS..115E4426H. doi:10.1073/pnas.1711788115. ISSN 0027-8424. PMC 5948952. PMID 29686092.
  12. ^ Park, Jeong-Heuy; Yamaguchi, Tetsutaro; Watanabe, Chiaki; Kawaguchi, Akira; Haneji, Kuniaki; Takeda, Mayako; Kim, Yong-Il; Tomoyasu, Yoko; Watanabe, Miyuki; Oota, Hiroki; Hanihara, Tsunehiko; Ishida, Hajime; Maki, Koutaro; Park, Soo-Byung; Kimura, Ryosuke (August 2012). "Effects of an Asian-specific nonsynonymous EDAR variant on multiple dental traits". Journal of Human Genetics. 57 (8): 508–514. doi:10.1038/jhg.2012.60. ISSN 1435-232X. PMID 22648185.
  13. ^ Adhikari K, Fuentes-Guajardo M, Quinto-Sánchez M, Mendoza-Revilla J, Camilo Chacón-Duque J, Acuña-Alonzo V, et al. (May 2016). "A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation". Nature Communications. 7: 11616. Bibcode:2016NatCo...711616A. doi:10.1038/ncomms11616. PMC 4874031. PMID 27193062.
  14. ^ Lozovschi, Alexandra (24 April 2018). "Ancient Teeth Reveal Breastfeeding-Related Gene Helped Early Americans Survive The Ice Age [Study]". Inquisitr. Retrieved 25 April 2018.
  15. ^ Nicholas Wade (February 14, 2013). "East Asian Physical Traits Linked to 35,000-Year-Old Mutation". The New York Times. Retrieved February 15, 2013.
  16. ^ Hlusko LJ, Carlson JP, Chaplin G, Elias SA, Hoffecker JF, Huffman M, et al. (May 2018). "Environmental selection during the last ice age on the mother-to-infant transmission of vitamin D and fatty acids through breast milk". Proceedings of the National Academy of Sciences of the United States of America. 115 (19): E4426–E4432. Bibcode:2018PNAS..115E4426H. doi:10.1073/pnas.1711788115. PMC 5948952. PMID 29686092.
  17. ^ Chang, Shie Hong; Jobling, Stephanie; Brennan, Keith; Headon, Denis J. (26 October 2009). "Enhanced Edar Signalling Has Pleiotropic Effects on Craniofacial and Cutaneous Glands". PLOS ONE. 4 (10): e7591. Bibcode:2009PLoSO...4.7591C. doi:10.1371/journal.pone.0007591. ISSN 1932-6203. PMC 2762540. PMID 19855838. "As this allele attained high frequency in an environment that was notably cold and dry, increased glandular secretions could represent a trait that was positively selected to achieve increased lubrication and reduced evaporation from exposed facial structures and upper airways"
  18. ^ Park JH, Yamaguchi T, Watanabe C, Kawaguchi A, Haneji K, Takeda M, Kim YI, Tomoyasu Y, Watanabe M, Oota H, Hanihara T, Ishida H, Maki K, Park SB, Kimura R (August 2012). "Effects of an Asian-specific nonsynonymous EDAR variant on multiple dental traits". Journal of Human Genetics. 57 (8): 508–14. doi:10.1038/jhg.2012.60. PMID 22648185.
  19. ^ Tan J, Peng Q, Li J, Guan Y, Zhang L, Jiao Y, Yang Y, Wang S, Jin L (May 2014). "Characteristics of dental morphology in the Xinjiang Uyghurs and correlation with the EDARV370A variant". Science China Life Sciences. 57 (5): 510–8. doi:10.1007/s11427-014-4654-x. PMID 24752358.
  20. ^ Adhikari, Kaustubh; Fuentes-Guajardo, Macarena; Quinto-Sánchez; Mendoza-Revilla; Camilo Chacón-Duque (2016). "A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation". Nature Communications. 7 (1): 11616. Bibcode:2016NatCo...711616A. doi:10.1038/ncomms11616. ISSN 2041-1723. PMC 4874031. PMID 27193062.
  21. ^ Wang, Chuan-Chao; Yeh, Hui-Yuan; Popov, Alexander N.; Zhang, Hu-Qin; Matsumura, Hirofumi; Sirak, Kendra; Cheronet, Olivia; Kovalev, Alexey; Rohland, Nadin; Kim, Alexander M.; Mallick, Swapan; Bernardos, Rebecca; Tumen, Dashtseveg; Zhao, Jing; Liu, Yi-Chang; Liu, Jiun-Yu; Mah, Matthew; Wang, Ke; Zhang, Zhao; Adamski, Nicole; Broomandkhoshbacht, Nasreen; Callan, Kimberly; Candilio, Francesca; Carlson, Kellie Sara Duffett; Culleton, Brendan J.; Eccles, Laurie; Freilich, Suzanne; Keating, Denise; Lawson, Ann Marie; Mandl, Kirsten; Michel, Megan; Oppenheimer, Jonas; Özdoğan, Kadir Toykan; Stewardson, Kristin; Wen, Shaoqing; Yan, Shi; Zalzala, Fatma; Chuang, Richard; Huang, Ching-Jung; Looh, Hana; Shiung, Chung-Ching; Nikitin, Yuri G.; Tabarev, Andrei V.; Tishkin, Alexey A.; Lin, Song; Sun, Zhou-Yong; Wu, Xiao-Ming; Yang, Tie-Lin; Hu, Xi; Chen, Liang; Du, Hua; Bayarsaikhan, Jamsranjav; Mijiddorj, Enkhbayar; Erdenebaatar, Diimaajav; Iderkhangai, Tumur-Ochir; Myagmar, Erdene; Kanzawa-Kiriyama, Hideaki; Nishino, Masato; Shinoda, Ken-ichi; Shubina, Olga A.; Guo, Jianxin; Cai, Wangwei; Deng, Qiongying; Kang, Longli; Li, Dawei; Li, Dongna; Lin, Rong; Shrestha, Rukesh; Wang, Ling-Xiang; Wei, Lanhai; Xie, Guangmao; Yao, Hongbing; Zhang, Manfei; He, Guanglin; Yang, Xiaomin; Hu, Rong; Robbeets, Martine; Schiffels, Stephan; Kennett, Douglas J.; Jin, Li; Li, Hui; Krause, Johannes; Pinhasi, Ron; Reich, David (March 2021). "Genomic insights into the formation of human populations in East Asia". Nature. 591 (7850): 413–419. Bibcode:2021Natur.591..413W. doi:10.1038/s41586-021-03336-2. ISSN 1476-4687. PMC 7993749. PMID 33618348.
  22. ^ Mathieson I, Lazaridis I, Rohland N, Mallick S, Patterson N, Roodenberg SA, et al. (December 2015). "Genome-wide patterns of selection in 230 ancient Eurasians". Nature. 528 (7583): 499–503. Bibcode:2015Natur.528..499M. doi:10.1038/nature16152. PMC 4918750. PMID 26595274.
  23. ^ Posth C, Nakatsuka N, Lazaridis I, Skoglund P, Mallick S, Lamnidis TC, et al. (November 2018). "Reconstructing the Deep Population History of Central and South America". Cell. 175 (5). Elsevier BV: 1185–1197.e22. doi:10.1016/j.cell.2018.10.027. hdl:10550/67985. PMC 6327247. PMID 30415837.
  24. ^ Wang, Chuan-Chao (March 2021). "Genomic insights into the formation of human populations in East Asia". Nature. 591 (7850): 413–419. Bibcode:2021Natur.591..413W. doi:10.1038/s41586-021-03336-2. ISSN 1476-4687. PMC 7993749. PMID 33618348. "None of our reported 6 Jomon individuals carries the derived allele at the EDARV370A variant in the human Ectodysplasin receptor which affects hair, sweat, and mammary glands (Online Table 15), which has been estimated to have arisen in mainland China ~30,000 years ago24 and then swept to high frequency in nearly all Holocene people from mainland East Asia and the Americas."

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