Human core duplicon gene families: game changers or game players?

Bekpen, Cemalettin; Tautz, Diethard

The repetitive nature of the spinal muscular atrophy (SMA) genes was first described [39] in the context of searching for candidate genes for SMA. However, SMA is caused by mutations in the duplicated copies of the SMN1 and SMN2 genes, which are located at chromosome 5q13.3 (reviewed in detail in [40] ). SMA core duplicon copies are located in close proximity both upstream and downstream (within approximately 50 kb) of the SMN2 gene. Therefore, to avoid confusion with the disease-causing genes, we will use the designation SMA-GUSBP to represent the SMA gene family. SMA-GUSBP genes are organized in 2 tandem and 10 dispersed copies along human chromosome 5; an additional copy is located on chromosome 6, and this is most slikely the ancestral copy. In the common ancestor of chimp and human, the ERV1/LTR12C retroviral element integrated upstream of SMA-GUSBP. In macaque, the GUSBP and ERV1/LTR12C elements are found in different chromosomal locations ( Supplementary Fig. 1 ). The SMA-GUSBP gene encodes a beta-glucuronidase-like domain ( Supplementary Fig. 2 ). No homologs of the SMA-GUSBP genes have been observed outside the great apes to date, i.e. it expanded specifically in the human lineage [10] . Therefore, SMA-GUSBP genes are the youngest expanded core duplicon family in humans.