Human Molecular Genetics Advance Access published online on August 7, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm209
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Characterization and evolution of the novel gene family FAM90A in primates originated by multiple duplication and rearrangement events
1 Genes and Disease Program, Center for Genomic Regulation (CRG-UPF), and CIBERESP, Barcelona, Catalonia, Spain 2 Department of Genetics and Microbiology, University of Bari, Bari, Italy 3 Experimental and Health Sciences Department, Pompeu Fabra University, Barcelona, Catalonia, Spain
* Correspondence should be addressed to: Xavier Estivill MD, PhD, Genes and Disease Program, Center for Genomic Regulation (CRG), Plaça Charles Darwin s/n (Carrer Dr Aiguader, 88), PRBB Building, Room 521, 08003 Barcelona, Catalonia, Spain, Tel. +34 93 316 0159, FAX +34 93 316 0099, e-mail: xavier.estivill{at}crg.es
Received April 17, 2007; Revised July 25, 2007; Accepted July 25, 2007
Genomic plasticity of human chromosome 8p23.1 region is highly influenced by two groups of complex segmental duplications (SDs), termed REPD and REPP, that mediate different kind of rearrangements. Part of the difficulty to explain the wide range of phenotypes associated to 8p23.1 rearrangements is that REPP and REPD are not yet well characterized, probably due to their polymorphic status. Here we describe a novel primate-specific gene family, named FAM90A (family with sequence similarity 90), found within these SDs. According to the current human reference sequence assembly, the FAM90A family includes 24 members along 8p23.1 region and another one on chromosome 12p13.31, showing copy number variation (CNV) between individuals. These genes can be classified into subfamilies I and II, which differ in their upstream and 5' UTR sequences but both share the same ORF and are ubiquitously expressed. Sequence analysis and comparative FISH studies showed that FAM90A Subfamily II suffered a big expansion in the hominoid lineage, whereas Subfamily I members were likely generated some time around the divergence of orangutan and African great apes by a fusion process. In addition, the analysis of the Ka/Ks ratios provides evidence of functional constraint of some FAM90A genes in all species. The characterization of the FAM90A gene family contributes to a better understanding of the structural polymorphism of the human 8p23.1 region, and constitutes a good example of how SDs, CNVs and rearrangements within themselves can promote the formation of new gene sequences with potential functional consequences.