OBJECTIVE:The objective of this paper is to explore the role that somatic mutations might play in the development of multiple sclerosis.
METHODS:We exome-sequenced in total 21 individual CD4+ lymphocytes isolated from cerebrospinal fluid of two patients. In addition we sequenced DNA from the patients’ peripheral blood to serve as germline reference.
RESULTS:In comparison with the respective germline sequence, each cell differed at an average of 1784 positions, but as anticipated subsequent analysis confirms that most, if not all, of these potential mutations are likely to represent artefacts generated during the amplification of a single genome and/or by sequencing. Fifty-six of the potential mutations were predicted to have likely functional effects on genes that have previously been implicated by GWAS, including three in the CD6 gene.
CONCLUSION: More robust methods applied to larger numbers of cells will be needed to define the role of somatic mutations.
When DNA is made into a protein the introns (non-coding bits) of DNA are removed to have RNA made up of exons (coding bits) of the DNA, this can be sequenced to see what proteins are likely to be made.
Exome sequencing (also known as targeted exome capture) is an efficient strategy to selectively sequence the coding regions of the genome as a cheaper but still effective alternative to whole genome sequencing. Exons are short, functionally important sequences of DNA which, together, represent only slightly more than the portion of the genome that is actually translated into protein. Exons are flanked by untranslated regions (UTR) that are usually not included in exome studies. In the human genome there are about 180,000 exons. These constitute about 1% of the human genome.
A phenome is the set of all phenotypes expressed by a cell, tissue, organ, organism, or species. Just as the genome and proteome signify all of an organism’s genes and proteins, the phenome represents the sum total of its phenotypic traits. Examples of human phenotypic traits are skin color, eye color, body height, or specific personality characteristics. Although any phenotype of any organism has a basis in its genotype, phenotypic expression may be influenced by environmental influences, mutation, and genetic variation such as single nucleotide polymorphisms (SNPs), or a combination of these factors.
Carroll RJ, Bastarache L, Denny JC. R PheWAS: Data Analysis and Plotting Tools for Phenome Wide Association Studies in the R Environment. Bioinformatics. 2014 Apr . [Epub ahead of print]