This web page was produced as an assignment for Genetics 564, an undergraduate course at UW-Madison
SLC6A4 Gene
Solute carrier family 6 (neurotransmitter transporter, member 4 (SLC6A4) is a gene on chromosome 17 in Homo sapiens at location 17q11.2. There are twelve introns and 14 exons composing the gene, which is about 6,500 bp in length [1].
Homo sapiens (Human) Solute carrier family 6 (neurotransmitter transporter), member 4 (SLC6A4) Accession Number: NM_001045.5 Length: 6,615 bp |
Several alleles and polymorphisms are thought to contribute to OCD. Three are 17-bp tandem repeats within intron 2 named STin2.9, STin2.10, and STin2.12 respectively (see figure 1 below) [2]. Another that has been strongly linked with OCD is a 44-bp insertion or deletion sequence in the 5-HTT region of the gene. This creates a long (L) and short (S) version of the gene. There is also a point mutation within the L allele which substitutes an adenine with a guanine to give LA and LG alleles (see figure 2 below) [3].
Figure 1: 17-bp tandem repeats within intron 2, constituting three of the common SLC6A4 alleles that are associated with OCD.
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Figure 2: 44-bp insertion sequence that distinguishes the L and S alleles. There is a point mutation within the L allele that changes adenine to guanine, making an LA and LG version of the L allele.
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The L alleles have been shown to cause an increase in transcription in the SLC6A4 gene, causing an increase in the number of SLC6A4 proteins that are created and inserted into the membrane. With more proteins there is more uptake of serotonin, leading to ultimately lowered levels of serotonin in the synaptic gap.
References
[1] SLC6A4 gene. (2015, February 9). Retrieved February 15, 2015, from http://ghr.nlm.nih.gov/gene/SLC6A4
[2] Ogilvie, A., Battersby, S., Fink, G., Harmar, A., Goodwin, G., Bubb, V., & Smith, C. (1996). Polymorphism in serotonin transporter gene associated with susceptibility to major depression. The Lancet, 347(9003), 731-733. Retrieved February 18, 2015, from http://www.sciencedirect.com.ezproxy.library.wisc.edu/science/article/pii/S0140673696900793
[3] Nakamura, M., Ueno, S., Sano, A., & Tanabe, H. (2000). The human serotonin transporter gene linked polymorphism (5-HTTLPR) shows ten novel allelic variants. Molecular Psychiatry, 5(1), 32-38. Retrieved February 19, 2015, from http://www.nature.com/mp/journal/v5/n1/full/4000698a.html
[2] Ogilvie, A., Battersby, S., Fink, G., Harmar, A., Goodwin, G., Bubb, V., & Smith, C. (1996). Polymorphism in serotonin transporter gene associated with susceptibility to major depression. The Lancet, 347(9003), 731-733. Retrieved February 18, 2015, from http://www.sciencedirect.com.ezproxy.library.wisc.edu/science/article/pii/S0140673696900793
[3] Nakamura, M., Ueno, S., Sano, A., & Tanabe, H. (2000). The human serotonin transporter gene linked polymorphism (5-HTTLPR) shows ten novel allelic variants. Molecular Psychiatry, 5(1), 32-38. Retrieved February 19, 2015, from http://www.nature.com/mp/journal/v5/n1/full/4000698a.html