ectodysplasin A receptor

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. It is structurally related to members of the TNF receptor superfamily.

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.

Clinical significance

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

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 and Native Americans but not common in African or European populations, is thought to be one of the key genes responsible for a number of differences between these populations, including the thicker hair, more numerous sweat glands, smaller breasts, and the Sinodont dentition (so-called shovel incisors) characteristic of East Asians. 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 breast milk under Vitamin D-poor conditions. The 370A mutation arose in humans approximately 35,000 years ago, and now is found in 60-90% of Han Chinese and in the majority of people in nearby Asian populations of very specific demographic haplogroups. This mutation is also implicated in ear morphology differences and reduced chin protrusion. 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 contract for foreign population from Africa, Europe, or Asia. This 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%).

A more recent study found 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. While the gene allele has some effects onto hair texture, such as thickness and straightness, it is not the origin of East Asian phenotypes, as much more alleles play a role in shaping human appearance. Another factor are skull shape and morphology, and low nasal bone, which are unaffected by the EDAR gene.

In a 2015 study, three (of six) 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.

In 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.

See also

*Ectodysplasin A2 receptor

References

Further reading

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External links

GeneReview/NIH/UW entry on Hypohidrotic Ectodermal Dysplasia

{{ci, date=June 2022

Proteins
Cell-surface receptors
Ectoderm
TNF receptor family