High-throughput single-nucleotide polymorphism discovery and the search for candidate genes for long-term SIVmac nonprogression in Chinese rhesus macaques (Macaca mulatta)

Abstract

Background: Genetic differences between Indian and Chinese rhesus macaques contribute to the phenotypic variance of clinical trials, including infection with SIVmac. The completion of the rhesus genome has facilitated the discovery of several thousand markers.

Methods: We developed a genome-wide SNP map for rhesus macaques containing 3869 validated markers with an average distance of 0.88 Mb and used the program VarLD to identify genomic areas with significant differences in linkage disequilibrium (LD) between Indian-derived and Chinese rhesus macaques.

Results: Forty-one statistically significant differences in LD between Chinese and Indian-origin rhesus were detected on chromosomes 1, 4, 5 and 11. The region of greatest LD difference was located on the proximal end of chromosome one, which also contained the genes ELAVL4, MAST2 and HIVEP3.

Conclusion: These genomic areas provide entry to more detailed studies of gene function. This method is also applicable to the study of differences in biomarkers between regional populations of other species.

Figure 1

Predicted and actual average distance between markers on each chromosome. When all chromosomes were combined, the average distance was 0.88 Mb.

Figure 2

Chromosomes with significant standardized VarLD scores. The small dashed line represents the 99.99^th percentile, the medium dashed line the 99^th percentile and the broad dashed line the 95^th percentile.