Genomic targets for high-resolution inference of kinship, ancestry and disease susceptibility in orang-utans (genus: Pon
- PDF / 576,944 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 3 Downloads / 212 Views
RESEARCH ARTICLE
Open Access
Genomic targets for high-resolution inference of kinship, ancestry and disease susceptibility in orang-utans (genus: Pongo) Graham L. Banes1* , Emily D. Fountain1, Alyssa Karklus2, Hao-Ming Huang3, Nian-Hong Jang-Liaw3, Daniel L. Burgess4,5, Jennifer Wendt4,6, Cynthia Moehlenkamp4,7 and George F. Mayhew4
Abstract 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: Ancestry informative markers, Cardiac disease, Chronic respiratory disease, Pedigree reconstruction, Baits, In-solution capture, ACMG v2.0
Background Advances in analytic molecular methods have gradually shed light on the evolutionary history of orang-utans (Pongo spp.). Protein electrophoretic studies, beginning in the 1970s [1, 2], first supported the description of two subspecies, distinct to the islands of Borneo and * Correspondence: [email protected] 1 Wisconsin National Primate Research Center, University of Wisconsin– Madison, 1220 Capitol Court, Madison, WI 53715, USA Full list of author information is available at the end of the article
Sumatra. Each was upgraded to species in 2000, following complete mitochondrial genome sequencing [3], and Bornean orang-utans were split into subspecies in 2003, based largely on further mitochondrial data [4, 5]. The first orang-utan reference genome was generated in 2011 [6], before the genus was split into three species in 2017, following whole genome re-sequencing of a previously understudied population [
Data Loading...
