SNPs+and+Triplet+repeats

=Searching for the source =

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Researchers have been trying to identify exactly what mutation in the androgen receptor for almost twenty years. What was once referred to as the culprit in several years earlier has been disproved and replaced several times since the 1990s. This is due to AR's tendency for linkage disequilibrium and a lack of a proper lab model. Here we will take a look at some of the important AR gene regions that have been investigated for AGA relationships ======

=Triplet Repeat Polymorphisms =

--The polyglutamine (CAG) Repeat--
Located on chromosome X at bp 66,548,181, this repeat varies from fewer than 10 repeats to 36 repeats. Studies have searched to link this repeat with AGA development but have found that it is not directly associated with AGA. The shorter CAG repeats have been linked with higher AR mRNA and protein levels so it is hypothesized that the hair follicle cells lack the ability or cofactor to interact with the CAG region. These shorter CAG repeats have been linked to prostate cancer development. The development of spinal and bulbar muscular atrophy, where CAG is repeated 38 to 60 times,researchers have found that the additional size interferes with nerve cells. It is also under investigation whether this repeat has an importance to breast cancer susceptibility. (5)

--The polyglycine (GGN) Repeat--
Located on chromosome X at bp 66,549,360, this repeat was previously identified as strongly associated with AGA. Shorter GGN repeats were directly associated with higher protein levels and higher AR activity. In one study GGN-23 (23 repeats of GGN) showed significant statistics in AGA affected vs unaffected. This association has since been considered a linkage disequilibrium between the GGN repeat and the believed causative mutation. (7) =Single Nucleotide Polymorphisms =

--SNP rs6152--
Chromosome X 66,765,627G>A. http://useast.ensembl.org/Homo_sapiens/Variation/Summary?r=X:66765127-66766127;v=rs6152;vdb=variation;vf=16128247 Here we see the most recent and strongest association of mutation to AGA. Unfortunately, due to the large amount of linkage disequilibrium upstream on the AR gene it is difficult to tell exactly what SNP is the source of AGA expression. (4)  http://genome.ucsc.edu/cgi-bin/hgTracks This image shows several documented SNPs (The black lines are more common then the red lines) upstream from the Rs6152 SNP.

**Research to identify the exact AGA coding region within the androgen receptor is still ongoing.**
Next: AGA Treatments

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<span class="reference-source text-font" style="font-family: Arial,Helvetica,sans-serif;">(4) <span class="reference-authors text-font" style="font-family: Arial,Helvetica,sans-serif;">Ellis, J. A., Scurrah, K. J., Cobb, J. E., Zaloumis, S. G., Duncan, A. E., Harrap, S. B. <span class="reference-title text-font" style="font-family: Arial,Helvetica,sans-serif;">Baldness and the androgen receptor: the AR polyglycine repeat polymorphism does not confer susceptibility to androgenetic alopecia. <span class="reference-source text-font" style="font-family: Arial,Helvetica,sans-serif;">Hum. Genet. 121: 451-457, 2007. <span style="font-family: Arial,Helvetica,sans-serif;"> (5)Ellis, J. A., Stebbing, M., Harrap, S. B. Polymorphism of the androgen receptor gene is associated with male pattern baldness. J. Invest. Derm. 116: 452-455, 2001. <span style="font-family: Arial,Helvetica,sans-serif;"> (7)Hillmer, A. M., Hanneken, S., Ritzmann, S., Becker, T., Freudenberg, J., Brockschmidt, F. F., Flaquer, A., Freudenberg-Hua, Y., Jamra, R. A., Metzen, C., Heyn, U., Schweiger, N., and 13 others. Genetic variation in the human androgen receptor gene is the major determinant of common early-onset androgenetic alopecia. Am. J. Hum. Genet. 77: 140-148, 2005.