Background: Orang-utans comprise three critically endangered species endemic to the islands of Borneo and Sumatra. Though whole-genome sequencing has recently accelerated our understanding of their evolutionary history, the costs of implementing routine genome screening and diagnostics remain prohibitive. Capitalizing on a tri-fold locus discovery approach, combining data from published whole-genome sequences, novel whole-exome sequencing, and microarray-derived genotype data, we aimed to develop a highly informative gene-focused panel of targets that can be used to address a broad range of research questions.
Results: We identified and present genomic co-ordinates for 175,186 SNPs and 2315 Y-chromosomal targets, plus 185 genes either known or presumed to be pathogenic in cardiovascular (N = 109) or respiratory (N = 43) diseases in humans - the primary and secondary causes of captive orang-utan mortality - or a majority of other human diseases (N = 33). As proof of concept, we designed and synthesized 'SeqCap' hybrid capture probes for these targets, demonstrating cost-effective target enrichment and reduced-representation sequencing.
Conclusions: Our targets are of broad utility in studies of orang-utan ancestry, admixture and disease susceptibility and aetiology, and thus are of value in addressing questions key to the survival of these species. To facilitate comparative analyses, these targets could now be standardized for future orang-utan population genomic studies. The targets are broadly compatible with commercial target enrichment platforms and can be utilized as published here to synthesize applicable probes.
Keywords: ACMG v2.0; Ancestry informative markers; Baits; Cardiac disease; Chronic respiratory disease; In-solution capture; Pedigree reconstruction.