Keawe Kali

BIOL 1615
Article Paper

The Role of Mutation Rate Variation and Genetic Diversity in the Architecture of Human Disease
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The article, The Role of Mutation Rate Variation and Genetic Diversity in the Architecture of
Human Disease, relates to a series of different important subjects that all coincide to determine
whether or not they increase the chances of having a disease gene. In the articles final findings, it is
determined that disease genes have substantially longer genes and they have greater intron diversity.
The authors of this article came to this conclusion after forming their hypothesis that high genic
mutation rates occur when the genes are associated with diseases than non-disease genes and that the
genic mutation rate is determined by the product of gene length, and the mutation rate of a locus
depends upon the rate of mutation per site and the number of sites at which a mutation can generate a
disease phenotype. Due to the difficulty of understanding what was being stated in the article, I took it
upon myself to research the various terms needed to be known in order to understand what is being
said, how they used their information gathered to come to their conclusions, and why this would be
considered important.
First, what needed to be understood was the basis of genetic construction and the many
different terms, therefore, a dictionary came into play. Words of importance to find were: Locus, allele,
gene, genome, gamete, bifurcating tree, intron, exon, stochastic, non-synonymous mutation, Mendelian
disease genes, deleterious mutations, single-nucleotide polymorphisms (SNPs), the genome-wide
association study (GWAS), GC-content (guanine-cytosine content), CDS (total coding sequence), etc.
Second, I took all that information and plugged it in, and what I found out was that they took
information from various studies online, such as GWAS, and cross referenced them with what they were
trying to disprove their hypothesis of intron divergence using the divergence between humans and
chimpanzees which in turn resulted in finding that the more intron diversity, the higher chance of a
disease gene. Another was through genealogy estimates, which stated that significantly longer and
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greater average genealogy lengths also lead to having disease gene association. By comparing these
three (Mendelian disease gene, GWAS gene, and non-disease gene) to each other, it helped to
determine what a disease resulted mostly from as compared to a gene that didnt have any disease
genes.
This is important to look into because of the possibility to finding cures through genetics. For
example, if the longer the gene possessed means that there is a higher risk of a disease gene being
present, then if the gene could be shortened by 30% (as the Mendelian disease is compared to a non-
disease gene) then possibly the disease itself will not appear. If there are greater intron diversities and
therefore more exon diversities that cause a gene to associate with a disease gene, then possibly by
finding a way to rewrite the coding to prevent these from appearing would help reduce the involvement
of a disease gene.
In conclusion, association with disease genes do not manifest with genome diversity but rather
with intron diversity and with a gene that has a substantially longer gene. By cross-referencing with data
given by GWAS, studies on the Mendelian disease gene, and using data of non-disease genes,
information about what is a likely cause of the formation of disease genes and where the base of
disease concentration, or genetic base, is found. With this information, the next step would be to
determine how to use this problem-solve and reduce any more disease genes in the human body.

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Bibliography
"Glossary." Genetics Home Reference. U.S. National Library of Medicine, Oct. 2013. Web. 15 July 2014.

The Role of Mutation Rate Variation and Genetic Diversity in the Architecture of Human Disease
Eyre-Walker YC, Eyre-Walker A (2014) The Role of Mutation Rate Variation and Genetic Diversity in the
Architecture of Human Disease. PLoS ONE 9(2): e90166. doi: 10.1371/journal.pone.0090166. Web. 10
June 2014.