Two new studies on exploring methods to study the structure of the human genome

Two similar papers published the latest issues of Nature and Genome Research do high-resolution analyses of the structure of the human genome. They differ in methodology, but have some cool conclusions. The Nature paper, “Mapping and sequencing of structural variation from eight human genomes,” created libraries of 4 African, 2 Asian, and 2 European genomes. From these libraries they created thousands of clones to figure out if there are structural variations in genomes of these eight individuals from diverse geographic ancestry.

The Genome Research paper, “Scanning the human genome at kilobase resolution,” used ditag genome scanning (DGS) to analyze the human genome in high resolution. This method is really similar to serial analysis of gene expression (SAGE), in that genome is fragmented, each tag is ligated with a marker, and a sequencing technique (454 in this particular study) is used ultimately to determine the origin of the fragment in genome. The authors of this paper report that their method was strong enough to provides a kilobase resolution for studying genome structure. DGS is also highly specific and can cover a lot of the genome. Downstream applications of DGS are to validate assembled genomes but also to compare genome similarity and variation in normal populations.

Both methods are able to identify genomic abnormalities like insertions, inversions, deletions, and translocations, much better than current technologies. But why is this all important to anthropology? The Nature paper shows how they were able to find 525 new insertion sequences that are not present in the human reference genome. These new insertion sequences are shown to be variable in copy number between individuals, which ultimately make for 525 new ancestry inherited markers. Furthermore, when the authors of the Nature paper sequenced their clones they were able to find an additional 261 structural variants which reveals considerable locus complexity and provides insights into the different mutational processes that have shaped the human genome.

One last point, most ancestry inherited markers have been SNPs, but more recent research on the human genome has shown, however, that larger-scale differences like the copy number variations (CNVs) and others screened in these two papers, may account for a great deal of genetic variation among individuals.

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    Kidd, J.M., Cooper, G.M., Donahue, W.F., Hayden, H.S., Sampas, N., Graves, T., Hansen, N., Teague, B., Alkan, C., Antonacci, F., Haugen, E., Zerr, T., Yamada, N.A., Tsang, P., Newman, T.L., Tüzün, E., Cheng, Z., Ebling, H.M., Tusneem, N., David, R., Gillett, W., Phelps, K.A., Weaver, M., Saranga, D., Brand, A., Tao, W., Gustafson, E., McKernan, K., Chen, L., Malig, M., Smith, J.D., Korn, J.M., McCarroll, S.A., Altshuler, D.A., Peiffer, D.A., Dorschner, M., Stamatoyannopoulos, J., Schwartz, D., Nickerson, D.A., Mullikin, J.C., Wilson, R.K., Bruhn, L., Olson, M.V., Kaul, R., Smith, D.R., Eichler, E.E. (2008). Mapping and sequencing of structural variation from eight human genomes. Nature, 453(7191), 56-64. DOI: 10.1038/nature06862
    Chen, J., Kim, Y.C., Jung, Y., Xuan, Z., Dworkin, G., Zhang, Y., Zhang, M.Q., Wang, S.M. (2008). Scanning the human genome at kilobase resolution. Genome Research DOI: 10.1101/gr.068304.107

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