The completion of the Human Genome
Project, sequencing of DNA and gene mapping, in 2003 laid the foundation for
in-depth gene specific disease research. Most recently, genome wide association
studies (GWAS) are being completed to uncover variations within individual
genes that may contribute to numerous diseases. GWAS scan markers through
genomes of many individuals to discover genetic variations that may be associated
with a particular disease (NIH 2013). One disease that has been widely studied
through GWAS analysis is rheumatoid arthritis (RA), an autoimmune disease that
causes severe joint inflammation, deformity, and chronic pain.
My
mother and sister both suffer from rheumatoid arthritis. It is likely that I
will also one day suffer from this autoimmune disease, as there are genetic
origins. This made me very curious to discover what these underlying genetic
mechanisms are. One recent genome wide association study meta-analysis, or
compilation of current research, was completed to examine functional mechanisms
that may underlie associations for RA. In this study, researchers were able to
examine publicly available data to discover 8 single nucleotide variations on 5
genes that are related to immune response through function (Deng 2013). The
ability to survey publicly available data to uncover the functional mechanisms
and locations of such disease associations can be a powerful tool to allow many
more people to access and analyze this GWAS data. Additionally, being able to
narrow down the specific locus, or location on a chromosome, where a mutation
is occurring will allow for better screening and potentially future
treatment/prevention of some diseases.
Another
GWAS analysis used data regarding a specific locus, CCR6, related to rheumatoid
arthritis in Japan. The researchers were able to use this data to create a
study specifically regarding this gene locus and screen study subjects for a
specific antibody and DNA sequence variation in CCR6 locus to determine risk
for development of rheumatoid arthritis. The study found that a variation in
the CCR6 gene locus was a risk factor for developing RA in females but
conversely was a protective factor against disease development in males (Teng
2012). The gender differences observed are not necessarily triggered by one
particular factor, but it was suggested that it could possibly be related to
individual environment. As environmental influence, nature vs. nurture, is
discussed in numerous fields from psychology to biochemistry, these
associations have broad impacts.
Genome
wide association studies are the next step in identifying specific individual
genetic variations and disease implications. With all the information that is
available through the Internet, it can become concerning to think about all of
the implications of a single change within your entire genome causing a
disease. One thing to remember is that although we cannot consciously control
if our DNA is replicating correctly or not, we can control many aspects of our
health. Decreasing stress, eating healthily, and exercising regularly are all
things each person can control and will not only make you feel better, but can
also potentially prevent negative modifications within your genome.
Deng F, Lei S, Zhu H, Zhang
Y, Zhang Z. 2013. Integrative analyses for functional mechanisms underlying
associations for rheumatoid arthritis. J Rheumatol. 40;1063-1068.
National Institutes of
Health (NIH). 2013. Genome Wide Association Studies. Available From: http://www.genome.gov/20019523
Teng E, Leong K, Li H, Thong
B, Koh E, Loi P, Zhao Y, Tan E. 2012. Analysis of a genome-wide association
study-linked locus (CCR6) in Asian rheumatoid arthritis. DNA and Cell Biology.
32(4):607-610.
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ReplyDeleteSorry for the previous delete, but had to fix my references!
ReplyDeleteThis article stood out to me, because just last night I was thinking to myself how amazing it would be to wake up one day this week and not have any pain. Having been diagnosed with arthritis last year at 21 years old, I know first hand how important discoveries like this can be. These discoveries lead to better treatment options, offering pain-free days to patients with arthritis, which I can say definitely make a difference in the quality of life.
In this post, I know you are focusing on variations within a specific gene. However, I think it is important to also discuss gene-gene interactions. Many people have limited knowledge in genetics, so referring to nucleotide variations within specific genes may confuse some people into thinking that only those specific genetic variations contribute to RA. You did mention that environmental influences and everyday activities contribute to RA, but coming from a family with no scientific background, I feel it important to mention gene-gene interactions.
Numerous studies have found that gene-gene interactions increase susceptibility to RA. A study performed by Huang et al. found 14 significant interactions among 12 genes: PADI4, FCGR3, TNFRSF1B, ITGAV, BTLA, SLC22A4, IL3, VEGF, TNF, NFKBIL1, TRAF1-C5 and MIF (1). Further research increased the interaction networks to 23 significant interactions, with nine new interactions and five new genes. Interestingly, since HLA-DRB1 alleles are found to be associated with RA, Boudjema et al. characterized the HLA-DMA and DMB genes (2). They found that, on their own, the HLA-DM genes do not influence RA susceptibility. Combined, these studies point to the importance of looking at gene-gene interaction in understanding a disease. While it is imperative to find nucleotide variations within specific genes, as Kelsey wonderfully explains, it is also important to look at how gene-gene interactions can affect disease.
[1] Boudjema A, Petit-Teixeira E, Cornelis F, Benhamamouch S. HLA-DMA and DMB genes in rheumatoid arthritis. Tissue Antigens 79(3):155-156, 2012.
[2] Huang CH, Cong L, Xie J, Qioa B, Lo SH, Zheng T. Rheumatoid arthritis-associated gene-gene interaction network for rheumatoid arthritis candidate genes. BMC Proc. 3(Suppl 7): S75, 2009.
Jamie,
ReplyDeleteThat is definitely a helpful clarification! It can be quite technical to begin explaining genetics to an audience with a wide variety of scientific knowledge. So many things, such as gene-gene interactions, play important roles in how genes are expressed and sometimes modified which can potentially cause disease. This is essentially what the field of epigenetics is examining when looking at how modifications outside of DNA sequence changes occur to cause phenotypic (expressional) changes. It is incredible the number of ways that disease can occur but also the ways that our bodies have developed mechanisms to counteract these possible manifestations!