ScienceDaily (Oct. 8, 2009) — In research published in Nature, an international team describes the finest map of changes to the structure of human genomes and a resource they have developed for researchers worldwide to look at the role of these changes in human disease. They also identify 75 'jumping genes' -- regions of our genome that can be found in more than one location in some individuals.
Chromosomes are shown color-coded in the outermost circle. Inside are lines connecting the origin and the new location (where known) of 58 out of 75 putative inter-chromosomal duplications, colored according to their chromosome of origin. (Credit: Jan Aerts, Wellcome Trust Sanger Institute)
However, the team cautions that they have not found large numbers of candidates that might alter susceptibility to complex diseases such as diabetes or heart disease among the common structural variants. They suggest strategies for finding this 'dark matter' of genetic variation.
Human genomes differ because of single-letter variations in the genetic code and also because whole segments of the code might be deleted or multiplied in different human genomes. These larger, structural differences are called copy number variants (CNVs).
The new research to map and characterize CNVs is of a scale and a power unmatched to date, involving hundreds of human genomes, billions of data points and many thousands of CNVs.
"This study is more than ten times as powerful as our first map, published three years ago," explains Dr Matt Hurles from the Wellcome Trust Sanger Institute and a leader on the project, "and much more detailed than any other. Importantly, we have also assigned the CNVs to a specific genetic background so that they can be readily examined in disease studies carried out by others, such as the Wellcome Trust Case Control Consortium.
"Nevertheless, we have not found large numbers of common CNVs that we can tie strongly to disease. There remains much to be discovered and much to understand and our freely available genotyped collection will drive that discovery."
The results show that any two genomes differ by more than 1000 CNVs, or around 0.8% of a person's genome sequence. Most of these CNVs are deletions, with a minority being duplications.
Two consequences are particularly striking in this study of apparently healthy people. First, 75 regions have jumped around in the genomes of these samples: second, more than 250 genes can lose one of the two copies in our genome without obvious consequences and a further 56 genes can fuse together potentially to form new composite genes.
"This paper detailing common CNVs in different world populations, and providing the first glimpse into evolutionary biology of such class of human variation, is unquestionably one of the most important advances in human genome research since the completion of a reference human genome," says Professor James R. Lupski, Vice Chair of the department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas. "It complements the cataloguing of single nucleotide variation delineated in the HapMap Project and will both enable some new approaches to, and further augment other studies of, basic human biology relevant to health and disease."
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Journal reference:
Conrad DF, Pinto D et al. Copy number variation in the human genome: mechanism, selection and disease. Nature, 2009; DOI: 10.1038/nature08516
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