The National Human Genome Research Institute (NHGRI), one of the National Institutes of Health (NIH), has announced its latest round of sequencing targets, with an emphasis on enhancing the understanding of how human genes function and how genomic differences between individuals influence the risk of health and disease.
The National Advisory Council for Human Genome Research, which is a federally chartered committee that advises NHGRI on program priorities and goals, recently approved three plans to specify the targets as part of its comprehensive strategy for NHGRI's Large-Scale Sequencing Research Network.
"The goal of our sequencing program is to build the most powerful toolbox possible for advancing human health. By identifying and seeking to fill crucial gaps in our knowledge, these new sequencing plans represent yet another important step in that direction," said NHGRI Director Francis S. Collins, M.D., Ph.D.
The plan given the priority is a project to identify structural variations in the human genome, which will characterize the most common types of structural variation in human DNA.
The effort will use 48 human DNA samples donated for the recently completed International HapMap Project, which produced a comprehensive catalog of human genetic variation, or haplotypes, designed to speed the search for genes involved in common diseases.
The HapMap identified neighborhoods of tiny changes in DNA - known as single nucleotide polymorphisms - that can be involved in human disease.
The structural variation effort will seek to identify instances where larger segments of DNA have been deleted, duplicated or rearranged - all of which can cause disease by disrupting the structure and function of genes.
A recent analysis has shown that these large-scale structural variations are much more common than previously appreciated. In fact, the genomes of any two humans are thought to differ by several hundred insertions, deletions and inversions.
The second plan will add DNA sequence to existing draft sequences of a number of primate species and add additional sequence information in regions of high biological interest within those genomes.
The increased coverage - a high-density genome sequence - will allow for an even better understanding of the factors contributing to the evolution of the human genome.
The primates chosen for this "index species" effort are rhesus macacque ("Macaca mulatta"), marmoset ("Callithrix jacchus") and orangutan ("Pongo pygmaeus").
In the future, NHGRI intends to add other organisms to the list of index species for which high-density genome sequences are desirable.
The third plan includes sequencing the genomes of eight new mammals at low-density draft coverage, which will be generated by sequencing their genomes at two-fold coverage.
That will bring to 24 the number of mammalian genomes sequenced at two-fold coverage, in addition to human and another seven mammalian genomes in draft or finished form sequenced by NHGRI-supported centers and made freely available in public databases.
Scientists will use the combined data to look for features that are similar, or conserved, among the genomes of the human and other mammals.
According to computer modeling results, it is expected that comparisons among the 24 genome sequences will allow conserved sequences as small as six base pairs to be identified reliably.