Research

Refinement of a chimpanzee pericentric inversion breakpoint to a segmental duplication cluster

Devin P Locke¹, Nicoletta Archidiacono², Doriana Misceo², Maria F Cardone², Stephane Deschamps³, Bruce Roe³, Mariano Rocchi² and Evan E Eichler^1*

• * Corresponding author: Evan E Eichler eee@cwru.edu

Author Affiliations

¹ Department of Genetics, Center for Computational Genomics and Center for Human Genetics, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, 10900 Euclid Avenue, Cleveland, OH 44106, USA

² Dipartimento di Anatomia Patologica e di Genetica, Sezione di Genetica, University of Bari, Bari 70126, Italy

³ Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019, USA

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Genome Biology 2003, 4:R50 doi:10.1186/gb-2003-4-8-r50

Published: 15 July 2003

Abstract

Background

Pericentric inversions are the most common euchromatic chromosomal differences among humans and the great apes. The human and chimpanzee karyotype differs by nine such events, in addition to several constitutive heterochromatic increases and one chromosomal fusion event. Reproductive isolation and subsequent speciation are thought to be the potential result of pericentric inversions, as reproductive boundaries form as a result of hybrid sterility.

Results

Here we employed a comparative fluorescence in situ hybridization approach, using probes selected from a combination of physical mapping, genomic sequence, and segmental duplication analyses to narrow the breakpoint interval of a pericentric inversion in chimpanzee involving the orthologous human 15q11-q13 region. We have refined the inversion breakpoint of this chimpanzee-specific rearrangement to a 600 kilobase (kb) interval of the human genome consisting of entirely duplicated material. Detailed analysis of the underlying sequence indicated that this region comprises multiple segmental duplications, including a previously characterized duplication of the alpha7 neuronal nicotinic acetylcholine receptor subunit gene (CHRNA7) in 15q13.3 and several Golgin-linked-to-PML, or LCR15, duplications.

Conclusions

We conclude that, on the basis of experimental data excluding the CHRNA7 duplicon as the site of inversion, and sequence analysis of regional duplications, the most likely rearrangement site is within a GLP/LCR15 duplicon. This study further exemplifies the genomic plasticity due to the presence of segmental duplications and highlights their importance for a complete understanding of genome evolution.