Identification of large-scale human-specific copy number differences by inter-species array comparative genomic hybridization.

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: Goidts, V.; Armengol, L.; Schempp, W.; Conroy, J.; Nowak, N.; Müller, S.; Cooper, D. N.; Estivill, X.; Enard, W.; Szamalek, J. M.; Hameister, H.; Kehrer-Sawatzki, H.
Year of Publication: 2006
Journal: Hum Genet
Volume: 119
Issue: 1-2
Pagination: 185-98
Date Published: 03/2006
Publication Language: eng
ISSN: 0340-6717
Keywords: Animals, Chromosomes, Artificial, Bacterial, Gene Dosage, Gene Duplication, Genome, Human, Gorilla gorilla, Humans, In Situ Hybridization, Fluorescence, Macaca, Microarray Analysis, Nucleic Acid Hybridization, Pan paniscus, Pan troglodytes, Pongo pygmaeus, Species Specificity

Copy number differences (CNDs), and the concomitant differences in gene number, have contributed significantly to the genomic divergence between humans and other primates. To assess its relative importance, the genomes of human, common chimpanzee, bonobo, gorilla, orangutan and macaque were compared by comparative genomic hybridization using a high-resolution human BAC array (aCGH). In an attempt to avoid potential interference from frequent intra-species polymorphism, pooled DNA samples were used from each species. A total of 322 sites of large-scale inter-species CND were identified. Most CNDs were lineage-specific but frequencies differed considerably between the lineages; the highest CND frequency among hominoids was observed in gorilla. The conserved nature of the orangutan genome has already been noted by karyotypic studies and our findings suggest that this degree of conservation may extend to the sub-microscopic level. Of the 322 CND sites identified, 14 human lineage-specific gains were observed. Most of these human-specific copy number gains span regions previously identified as segmental duplications (SDs) and our study demonstrates that SDs are major sites of CND between the genomes of humans and other primates. Four of the human-specific CNDs detected by aCGH map close to the breakpoints of human-specific karyotypic changes [e.g., the human-specific inversion of chromosome 1 and the polymorphic inversion inv(2)(p11.2q13)], suggesting that human-specific duplications may have predisposed to chromosomal rearrangement. The association of human-specific copy number gains with chromosomal breakpoints emphasizes their potential importance in mediating karyotypic evolution as well as in promoting human genomic diversity.

DOI: 10.1007/s00439-005-0130-9
Alternate Journal: Hum. Genet.