This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.
DNA Sequence
Gene Accession number: NG_009014
The gene (AR) was sequenced in 1989 (1). It is located at Xq11.2-q12. AR is more than 90 kb long and contains two splice variants (entrez-gene and genecards).
DNA Motifs
In order to determine if there are DNA motifs in the androgen receptor gene (AR), I used the MOTIF program (http://motif.genome.jp). I used the mRNA of the longer splice variant as the entire DNA sequence is much too large for the program to handle (entrez-nucleotide: see mRNAs). The longer mRNA codes for a protein containing the androgen receptor. The program identified with a 100% cut off 10 motifs for the longer splice variant.
The program identified the following DNA motifs: heat shock factor (drosophila), heat shock factor (yeast), alcohol dehydrogenase gene regulator 1, NF-kappaB (p65), NF-kappaB, activator nitrogen-regulator genes, sex-determining region Y gene product, homeo domain factor Nkx-2.5/Csx tinman homolog, and runt-factor AML-1.
The sex-determing Y gene product motif was expected. AR is linked to sexual development of the male (1, 2, 3). The heat shock factor motifs appear to be commonly shared by many different genes and signify more of an evolutionary trait unrelated to the phenotype, i.e. survival of protein product. A mutation in said motif could interrupt functionality of the gene product at certain higher temperatures and could lead to an incompletely penetrant androgen insensitivity syndrome phenotype. The alcohol dehydrogenase gene regulator 1 (ADR1) motif is likely part of the DNA binding motif. According to entrez-nucleotide, ADR1 could be a zinc finger protein involved in DNA binding of Candida albicans (4). NF-kappaB motif is also found in TNFAIP3 interacting protein 2. This protein is a transcription factor (5). This motif could also be part of the DNA binding domain of AR. The Nkx-2.5/Csx tinman homolog is a transcription factor motif is also related to DNA binding. The final motif, runt-factor AML-1, is a heterodimeric transcription factor like the androgen recptor. These results are congruent with its function as a transcription factor. Any mutation here would likely lead to either complete or mild AIS.
References
1. Lubahn, D., Brown, T., Simental, J., Higgs, H., Migeon, C., Wilson, E., French, F. (1989). Sequence of the intron/exon junctions of the coding region of the human androgen receptor gene and identification of a point mutation in a family with complete androgen insensitivity syndrome. Proc. Natl. Acad. Sci 86. Retrieved from: http://www.jstor.org/stable/35117?seq=1
2. Diamond, M., Watson, L. A. (2004). Androgen insensitivity and Klinefelter's syndrome: sex and gender considerations. Child Adolesc Psychiatric Clin N. Arm. of North America 13. Retrieved from: http://www.hawaii.edu/PCSS/online_artcls/intersex/AndrogenInsensitivity.htm
3. Galani, A., Kitsiou-Tzeli, S., Sofokleous, C., Kanavakis, E., Kalpini-Mavrou, A. (2008). Androgen insensitivity syndrome: clinical features and molecular defects. HORMONES 7(3). Retrieved from: http://hormones.gr/preview.php?c_id=227
4. Jones, T., Federspiel, N., Chibana, H., Dungan, J., Kalman, S., Magee, B., Newport, G., Thorstenson, Y., Agabian, N., Magee, P., Davis, R., Sherer, S. (2004). The diploid genome sequence of Candida albicans. PNAS 101(19). doi: 10.1073
5. Bouwmeester, T., Bauch, A., Ruffner, H., Angrand, P, Bergamini, G., Croughton, K., Cruciat, C., Eberhard, D., Gagneur, J., Ghidelli, T., Hopf, C., Huhse, B., Mangano, R., Michon, A., Schirle, M., Schlegl, J., Schwab, M., Stein, M., Bauer, A., Casari, G., Drewes, G., Gavin, A., Jackson, D., Joberty, G., Neubauer, G., Rick, J., Kuster, B., Superti-Furga G. (2004). A physical and functional map of the human TNF-alpha/NF-kappaB signal transduction pathway. Nature Cell Biology 6. doi: 10.1038
Website authored by Sam Trammell. Email: [email protected]. Last updated: February 28, 2009.
