Analysis of 100 high-coverage genomes from a pedigreed captive baboon colony

Abstract

Baboons (genus Papio) are broadly studied in the wild and in captivity. They are widely used as a nonhuman primate model for biomedical studies, and the Southwest National Primate Research Center (SNPRC) at Texas Biomedical Research Institute has maintained a large captive baboon colony for more than 50 yr. Unlike other model organisms, however, the genomic resources for baboons are severely lacking. This has hindered the progress of studies using baboons as a model for basic biology or human disease. Here, we describe a data set of 100 high-coverage whole-genome sequences obtained from the mixed colony of olive (P. anubis) and yellow (P. cynocephalus) baboons housed at the SNPRC. These data provide a comprehensive catalog of common genetic variation in baboons, as well as a fine-scale genetic map. We show how the data can be used to learn about ancestry and admixture and to correct errors in the colony records. Finally, we investigated the consequences of inbreeding within the SNPRC colony and found clear evidence for increased rates of infant mortality and increased homozygosity of putatively deleterious alleles in inbred individuals.

A comparison of humans and baboons suggests germline mutation rates do not track cell divisions

“…A pairedend 150-bp library was prepared for each sample using the TruSeq DNA PCR-Free Library Prep Kit (Illumina), and sequenced on the Illumina HiSeq X platform. We expanded our initial 2-generation cohort by including sequences generated by a parallel project at the SNPRC on the Illumina HiSeq 2500 platform [58]. Thus, we analyzed a total of 29 baboons distributed into 2 pedigrees.…”

“…We then used bcftools isec (version1.3, www.htslib.org) to identify variants that were fully transmitted across all 4 generations of our baboon pedigree (i.e., variants in individuals 32043, 32849, and 33863 that were also observed in their respective parent, grandparents, and greatgrandparents), reasoning that these are likely real polymorphisms [66]. Our second dataset consisted of the SNP and indel variants called by Robinson and colleagues in a sequencing panel of 100 baboons [58]. We excluded 14 baboons that overlapped with our pedigrees, leaving only variants called in the 86 unrelated baboons, which we subjected to a number of sitelevel "hard filters" as suggested by the GATK Best Practices workflow ("QualByDepth" > 2, "FisherStrand" < 60, "RMSMappingQuality" > 40, "MappingQualityRankSumTest" > −12.5, "ReadPosRankSumTest" > −8, "StrandOddsRatio" < 3 for SNPs) [41,58].…”

“…Our second dataset consisted of the SNP and indel variants called by Robinson and colleagues in a sequencing panel of 100 baboons [58]. We excluded 14 baboons that overlapped with our pedigrees, leaving only variants called in the 86 unrelated baboons, which we subjected to a number of sitelevel "hard filters" as suggested by the GATK Best Practices workflow ("QualByDepth" > 2, "FisherStrand" < 60, "RMSMappingQuality" > 40, "MappingQualityRankSumTest" > −12.5, "ReadPosRankSumTest" > −8, "StrandOddsRatio" < 3 for SNPs) [41,58]. The aforementioned procedure thus yielded 1 set of "known" variants for humans (from dbSNP) and 2 sets for baboons (from transmission and an 86-baboon sequencing panel).…”

Admixture in Mammals and How to Understand Its Functional Implications

“…Beyond great apes, large captive populations of other primates, like baboons or macaques, offer the opportunity to relate genotypes to phenotypes in their respective branches. For example, the genetic and phenotypic data from captive baboons of a mixed colony of two species will be a valuable resource to study the immediate impact of hybridization . In domesticated species, on the other hand, genotypic and phenotypic data on thousands of individuals allow to perform GWAS, which provides a rich resource for inferences on traits related to admixture.…”

“…It would be interesting to address such questions in other species, since this will guide interpretations on what we observe in humans. For example, in species such as baboons, hybridization can be studied either in the wild or in the artificial setting of captive animals, despite abundant inbreeding in the latter case. The first few generations of hybrids may also be studied in domesticated species, and in rare cases, aDNA potentially provides a historical perspective for the present‐day landscape.…”