Wednesday, 28 March 2012

Advances in genetic sequencing

Advances in genetic sequencing

The article “Exome sequencing identifies the cause of a mendelian disorder” published in January of 2010 has identified new ways of researching genetics especially those of rare diseases. This is exactly what a mendelian disorder is, an abnormality or mutation of the human genome (Reece J.B, p313-315). The aims and concepts discussed were the discovery of being able to distinguish these genes using the exome. As stated in the article “the exome sequencing of a small number of affected family members or affected unrelated individuals is a powerful, efficient and cost-efficient strategy.”

The research was to reveal which gene was causing Miller syndrome. This being a very rare disease, the number of subjects is limited the study only containing five, two sibling kindred’s and three other unrelated cases. Due to the large amount of information in genetics it was focused on the nonsynonymous variants, splice and donor site mutations and short coding insertions. It focused on these because they are notorious for creating issues like mutations and disease.

What was found was that the two sibling kindreds had several variants associated with the disorder; these were then compared to the other unrelated cases in which the gene DHODH was highlighted. Due the small amount of subjects it was needed to prove this finding, the null hypothesis was used to create a comparison. The null hypothesis would state that this specific gene was highlighted only by chance or coincidence. The p-value found was 0.000015 which makes it highly unlikely this would happen by chance in fact a 0.0015% chance of occurrence.

 What does this mean?

The gene DHODH encodes the enzyme dihydroorotate dehydrogenase. This enzyme is used to oxidize dihydroorotate to orotate. This is linked to the short-term energy supply and interrupts the normal growth of a fetus. It is not known how or why the mutation of this gene causes these specific abnormalities but with this knowledge, science is a step closer to clarifying this picture. It is believed that even if only one genome is mutated it results in the change of the entire genetic makeup (Chen J, M). Yet again another mystery about genetics.

Why is this important?

The discovery in using this method aids the research into rare diseases and makes it more cost efficient. Genomes hold so much information the easier it is for us to extract the more knowledge we can gain and improve our way of life.  Although there is still a lot we don’t know, each small discovery brings science one steps closer to an answer or another discovery in which will arise more and new questions.


Chen J, M. Frec C  et al. 2010 ‘Revealing the human mutome’ Clinical Genetics, vol. 78, p310-320

Ng S, B, Buckingham K, J. et al. 2010 ‘Exome sequencing identifies the cause of a mendelian disorder’, Nature Genetics vol. 42, no. 1, p30-36

Reece, Jane B; Meyers, Noel; Urry, Lisa A; Cain, Michael L; Wasserman, Steven A; Minorsky, Peter V; Jackson, Robert B; Cooke, Bernard N, 2012; Campbell Biology, Australian 9th Edition, Pearson, Australia p309-340

 By M. Yelorm

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