RT Journal Article
SR Electronic
T1 Improved full-length killer cell immunoglobulin-like receptor transcript discovery in Mauritian cynomolgus macaques
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 093559
DO 10.1101/093559
A1 Trent M. Prall
A1 Michael E. Graham
A1 Julie A. Karl
A1 Roger W. Wiseman
A1 Adam J. Ericsen
A1 Muthuswamy Raveendran
A1 R. Alan Harris
A1 Donna M. Muzny
A1 Richard A. Gibbs
A1 Jeffrey Rogers
A1 David H. O’Connor
YR 2016
UL http://biorxiv.org/content/early/2016/12/13/093559.abstract
AB Killer cell Immunoglobulin-like Receptors (KIRs) modulate disease progression of pathogens including HIV, malaria, and hepatitis C. Cynomolgus and rhesus macaques are widely used as nonhuman primate models to study human pathogens and so considerable effort has been put into characterizing their KIR genetics. However, previous studies have relied on cDNA cloning and Sanger sequencing that lacks the throughput of current sequencing platforms. In this study, we present a high throughput, full-length allele discovery method utilizing PacBio circular consensus sequencing (CCS). We also describe a new approach to Macaque Exome Sequencing (MES) and the development of the Rhexome1.0, an adapted target capture reagent that includes macaque-specific capture probesets. By using sequence reads generated by whole genome sequencing (WGS) and MES to inform primer design, we were able to increase the sensitivity of KIR allele discovery. We demonstrate this increased sensitivity by defining nine novel alleles within a cohort of Mauritian cynomolgus macaques (MCM), a geographically isolated population with restricted KIR genetics that was thought to be completely characterized. Finally, we describe an approach to genotyping KIRs directly from sequence reads generated using WGS/MES reads. The findings presented here expand our understanding of KIR genetics in MCM by associating new genes with all eight KIR haplotypes and demonstrating the existence of at least one KIR3DS gene associated with every haplotype.