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

Abstract

24 25 26 RUNNING TITLE 27 Genomic analysis of a pedigreed baboon colony 28 29 30 ABSTRACT 35 Baboons (genus Papio) are broadly studied in the wild and in captivity. They are widely 36 used as a non-human primate model for biomedical studies, and the Southwest National Primate 37Research Center (SNPRC) at Texas Biomedical Research Institute has maintained a large captive 38 baboon colony for more than 50 years. Unlike other model organisms though, the genomic 39 resources for baboons are severely lacking. This has hindered the progress of studies using 40 baboons as a model for basic biology or human disease. Here, we describe a dataset of 100 high-41coverage whole-genome sequences obtained from the mixed colony of olive (P. anubis) and 42 yellow (P. cynocephalus) baboons housed at the SNPRC. These data provide a comprehensive 43 catalog of common genetic variation in baboons, as well as a fine-scale genetic map. We show 44 how the data can be used to learn about ancestry and admixture, and to correct errors in the 45 colony records. Finally, we investigated the consequences of inbreeding within the SNPRC 46 colony and found clear evidence for increased rates of juvenile mortality and increased 47 homozygosity of putatively deleterious alleles in inbred individuals. 48 49

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

“…A paired-end 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 great-grandparents), 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 site-level “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 site-level “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).…”

Accurate assembly of the olive baboon (Papio anubis) genome using long-­read and Hi-C data

“…We estimated the scaled recombination rate ρ (= 4Nr where N is the effective population size and r is the recombination rate per generation) using LDhelmet [47] from 24 unrelated olive baboons [48]. We then identified potential breaks in synteny as regions with total ρ > 500 and ρ / bp > 0.2.…”

“…We considered only biallelic SNPs, and required a depth ≥ 15, QUAL > 50 and genotype quality (GQ) ≥ 40 in order to make a genotype call. We further required an allelic balance (AB) of > 0.3 for heterozygote calls and AB < 0.07 for homozygote calls, and excluded all repetitive regions as described in [48]. We focused our analyses on those SNPs that were most informative about recent crossover events.…”