Deciphered The Greatest Source Of Variability In The Human Genome

Five years after the publication of the initial sequence of the human genome, it has been uncovered that this sequence is not identical among different individuals and that the existing variability is ten times greater than it was supposed in the initial studies. Up to now it was thought that each person differed from another in a million of the more than 3 billion nucleotides (the letters in which information is encrypted in the genome sequence: A, C, G and T) that compose the human genome.

A study carried out by a Consortium of American, Spanish, Canadian, British and Japanese investigators has revealed that any two people differ in more than 20 million nucleotides, that are grouped in at least 1.400 discrete regions of the genome.

The difference between a person and another is not in the sequence itself but in a varying number of copies. Those regions, that are termed “Copy Number Variants” or CNVs, suppose more than 360 million differences with respect to the original sequence published in early 2003 by the International Human Genome Project Consortium.

The study of the structural variation of the human genome will be published in Nature, in the issue of November 23rd. This research, carried out in samples coming from individuals of Asian, African and European ancestry, represents the most exhaustive study of large-scale variability thus far published, after the definition of the reference sequence of the human genome and the study of nucleotide diversity (HapMap), published in this same journal by the end of 2005.

The work clearly shows that it does not exist a unique sequence of the human genome, but a plethora of different sequences. The 1.400 variable regions reported do indeed contain genes, besides of other functional structures, and many of them correspond to regions involved in human diseases, such as muscular dystrophies, renal and many other developmental disorders. Besides, the regions that have been detected do contain variants that could confer sensitivity or resistance for many common diseases that affect the population, like AIDS or the systemic lupus erythematosus (SLE), among others. The results of this investigation uncover a new dimension of the complexity of the human genome, unexpected and unexplored until now.

The discovery opens the doors to numerous studies to define the causes of many human diseases, to develop more efficient pharmacological processes and to develop prenatal screening methods, which will completely change the current methodologies for the prenatal diagnostic.

Local investigators, Lluis Armengol, Juan Ramon Gonzalez, Monica Gratacos and Xavier Estivill, from the group of Genetic Causes of Disease of the Program Genes and Disease, at the Centre for Genomic Regulation (CRG) are part of the international consortium and have participated in the work. The Spanish contribution to this research project has been supported by the Foundation Genome Spain.