Complex patterns of copy number variation at sites of segmental duplications: an important category of structural variation in the human genome. Export

@article{citeulike:801652, abstract = {The structural diversity of the human genome is much higher than previously assumed although its full extent remains unknown. To investigate the association between segmental duplications that display constitutive copy number differences (CNDs) between humans and the great apes and those which exhibit polymorphic copy number variations (CNVs) between humans, we analysed a BAC array enriched with segmental duplications displaying such CNDs. This study documents for the first time that in addition to human-specific gains common to all humans, these duplication clusters (DCs) also exhibit polymorphic CNVs > 40 kb. Segmental duplication is known to have been a frequent event during human genome evolution. Importantly, among the CNV-associated genes identified here, those involved in transcriptional regulation were found to be significantly overrepresented. Complex patterns of variation were evident at sites of DCs, manifesting as inter-individual differentially sized copy number alterations at the same genomic loci. Thus, CNVs associated with segmental duplications do not simply represent insertion/deletion polymorphisms, but rather constitute a wide variety of rearrangements involving differential amplification and partial gains and losses with high inter-individual variability. Although the number of CNVs was not found to differ between Africans and Caucasians/Asians, the average number of variant patterns per locus was significantly lower in Africans. Thus, complex variation patterns characterizing segmental duplications result from relatively recent genomic rearrangements. The high number of these rearrangements, some of which are potentially recurrent, together with differences in population size and expansion dynamics, may account for the greater diversity of CNV in Caucasians/Asians as compared with Africans.}, address = {Department of Human Genetics, University of Ulm, Albert Einstein Allee 11, 89081 , Ulm, Germany, hildegard.kehrer-sawatzki@uni-ulm.de.}, author = {Goidts, V. and Cooper, D. N. and Armengol, L. and Schempp, W. and Conroy, J. and Estivill, X. and Nowak, N. and Hameister, H. and Kehrer-Sawatzki, H.}, citeulike-article-id = {801652}, citeulike-linkout-0 = {http://dx.doi.org/10.1007/s00439-006-0217-y}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16838144}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16838144}, doi = {10.1007/s00439-006-0217-y}, issn = {0340-6717}, journal = {Hum Genet}, keywords = {autosomal, cnv}, month = {September}, number = {2}, pages = {270--284}, posted-at = {2006-12-09 11:05:46}, priority = {5}, title = {Complex patterns of copy number variation at sites of segmental duplications: an important category of structural variation in the human genome.}, url = {http://dx.doi.org/10.1007/s00439-006-0217-y}, volume = {120}, year = {2006} }

TY - JOUR ID - citeulike:801652 L3 - citeulike-article-id:801652 N2 - The structural diversity of the human genome is much higher than previously assumed although its full extent remains unknown. To investigate the association between segmental duplications that display constitutive copy number differences (CNDs) between humans and the great apes and those which exhibit polymorphic copy number variations (CNVs) between humans, we analysed a BAC array enriched with segmental duplications displaying such CNDs. This study documents for the first time that in addition to human-specific gains common to all humans, these duplication clusters (DCs) also exhibit polymorphic CNVs > 40 kb. Segmental duplication is known to have been a frequent event during human genome evolution. Importantly, among the CNV-associated genes identified here, those involved in transcriptional regulation were found to be significantly overrepresented. Complex patterns of variation were evident at sites of DCs, manifesting as inter-individual differentially sized copy number alterations at the same genomic loci. Thus, CNVs associated with segmental duplications do not simply represent insertion/deletion polymorphisms, but rather constitute a wide variety of rearrangements involving differential amplification and partial gains and losses with high inter-individual variability. Although the number of CNVs was not found to differ between Africans and Caucasians/Asians, the average number of variant patterns per locus was significantly lower in Africans. Thus, complex variation patterns characterizing segmental duplications result from relatively recent genomic rearrangements. The high number of these rearrangements, some of which are potentially recurrent, together with differences in population size and expansion dynamics, may account for the greater diversity of CNV in Caucasians/Asians as compared with Africans. IS - 2 JF - Hum Genet SN - 0340-6717 AD - Department of Human Genetics, University of Ulm, Albert Einstein Allee 11, 89081 , Ulm, Germany, hildegard.kehrer-sawatzki@uni-ulm.de. EP - 284 TI - Complex patterns of copy number variation at sites of segmental duplications: an important category of structural variation in the human genome. VL - 120 SP - 270 KW - autosomal KW - cnv AU - Goidts, V AU - Cooper, DN AU - Armengol, L AU - Schempp, W AU - Conroy, J AU - Estivill, X AU - Nowak, N AU - Hameister, H AU - Kehrer-Sawatzki, H PY - 2006/09// UR - http://dx.doi.org/10.1007/s00439-006-0217-y ER -