Search for somatic DNA variation in the brain: investigation of the serotonin 2A receptor gene.

Somatic DNA variation represents one of the most interesting but also one of the least investigated genetic phenomena. In addition to the classical case of DNA hypermutability at the V(D)J region, there is an increasing body of experimental evidence suggesting that genes other than immunoglobulin in tissues other than lymphocytes also exhibit nonuniformity of DNA sequence, which opens new opportunities for explaining various features of multicellular organisms. Identification of somatic DNA mutability, however, is not a trivial task and numerous confounding factors have to be taken into account. In this work we investigated putative DNA variation in the serotonin 2A receptor gene (HTR2A). A series of real-time PCR-based experiments was performed on DNA samples (n = 8) from human brain and peripheral leukocytes. Amplification of the target DNA sequences was carefully matched to that of the control plasmid containing the insert of HTR2A. Sequencing of nearly 500 clones containing a total of 150,000 nucleotides did not show any evidence for somatic DNA variation in the brain and peripheral leukocytes. It is argued in this article that although intraindividual DNA mutability may be a more common phenomenon than is generally accepted, some of the earlier claims of genetic nonidentity on the brain cells may be premature.