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Sequencing strategies and characterization of 721 vervet monkey genomes for future genetic analyses of medically relevant traits.

Huang YS, Ramensky V, Service SK, Jasinska AJ, Jung Y, Choi OW, Cantor RM, Juretic N, Wasserscheid J, Kaplan JR, Jorgensen MJ, Dyer TD, Dewar K, Blangero J, Wilson RK, Warren W, Weinstock GM, Freimer NB - BMC Biol. (2015)

Bottom Line: From high-depth WGS data we identified more than 4 million polymorphic unequivocal segregating sites; by pruning these SNPs based on heterozygosity, quality control filters, and the degree of linkage disequilibrium (LD) between SNPs, we constructed genome-wide panels suitable for genetic association (about 500,000 SNPs) and linkage analysis (about 150,000 SNPs).To further enhance the utility of these resources for linkage analysis, we used a further pruned subset of the linkage panel to generate multipoint identity by descent matrices.The genetic and phenotypic resources now available for the VRC and other Caribbean-origin vervets enable their use for genetic investigation of traits relevant to human diseases.

View Article: PubMed Central - PubMed

Affiliation: Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, CA, 90095, USA.

ABSTRACT

Background: We report here the first genome-wide high-resolution polymorphism resource for non-human primate (NHP) association and linkage studies, constructed for the Caribbean-origin vervet monkey, or African green monkey (Chlorocebus aethiops sabaeus), one of the most widely used NHPs in biomedical research. We generated this resource by whole genome sequencing (WGS) of monkeys from the Vervet Research Colony (VRC), an NIH-supported research resource for which extensive phenotypic data are available.

Results: We identified genome-wide single nucleotide polymorphisms (SNPs) by WGS of 721 members of an extended pedigree from the VRC. From high-depth WGS data we identified more than 4 million polymorphic unequivocal segregating sites; by pruning these SNPs based on heterozygosity, quality control filters, and the degree of linkage disequilibrium (LD) between SNPs, we constructed genome-wide panels suitable for genetic association (about 500,000 SNPs) and linkage analysis (about 150,000 SNPs). To further enhance the utility of these resources for linkage analysis, we used a further pruned subset of the linkage panel to generate multipoint identity by descent matrices.

Conclusions: The genetic and phenotypic resources now available for the VRC and other Caribbean-origin vervets enable their use for genetic investigation of traits relevant to human diseases.

No MeSH data available.


Boxplot of actual sequencing depth versus planned sequencing depth for the 725 monkeys in the WGS study
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Fig2: Boxplot of actual sequencing depth versus planned sequencing depth for the 725 monkeys in the WGS study

Mentions: Given improvements in technology over the course of the project, our sequencing protocol resulted, for a substantial proportion of samples, in considerably deeper coverage than had been our target (summary sequencing statistics for each monkey are given in Additional file 1: Table S1). As a result, the variation in sequencing depth, across the pedigree, is more accurately represented as a continuum than as three discrete bins (Fig. 2). For example, among the 406 monkeys targeted for 4–6× sequencing we achieved >20× average depth for 3 monkeys; 10–20× depth for 61 monkeys; and 6–10× depth for 36 monkeys. We considered “high coverage” monkeys to be a set of 17 monkeys, each with >25× average coverage, including the 16 monkeys initially chosen for high-depth sequencing and an additional monkey sequenced at a higher depth than originally planned.Fig. 2


Sequencing strategies and characterization of 721 vervet monkey genomes for future genetic analyses of medically relevant traits.

Huang YS, Ramensky V, Service SK, Jasinska AJ, Jung Y, Choi OW, Cantor RM, Juretic N, Wasserscheid J, Kaplan JR, Jorgensen MJ, Dyer TD, Dewar K, Blangero J, Wilson RK, Warren W, Weinstock GM, Freimer NB - BMC Biol. (2015)

Boxplot of actual sequencing depth versus planned sequencing depth for the 725 monkeys in the WGS study
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4494155&req=5

Fig2: Boxplot of actual sequencing depth versus planned sequencing depth for the 725 monkeys in the WGS study
Mentions: Given improvements in technology over the course of the project, our sequencing protocol resulted, for a substantial proportion of samples, in considerably deeper coverage than had been our target (summary sequencing statistics for each monkey are given in Additional file 1: Table S1). As a result, the variation in sequencing depth, across the pedigree, is more accurately represented as a continuum than as three discrete bins (Fig. 2). For example, among the 406 monkeys targeted for 4–6× sequencing we achieved >20× average depth for 3 monkeys; 10–20× depth for 61 monkeys; and 6–10× depth for 36 monkeys. We considered “high coverage” monkeys to be a set of 17 monkeys, each with >25× average coverage, including the 16 monkeys initially chosen for high-depth sequencing and an additional monkey sequenced at a higher depth than originally planned.Fig. 2

Bottom Line: From high-depth WGS data we identified more than 4 million polymorphic unequivocal segregating sites; by pruning these SNPs based on heterozygosity, quality control filters, and the degree of linkage disequilibrium (LD) between SNPs, we constructed genome-wide panels suitable for genetic association (about 500,000 SNPs) and linkage analysis (about 150,000 SNPs).To further enhance the utility of these resources for linkage analysis, we used a further pruned subset of the linkage panel to generate multipoint identity by descent matrices.The genetic and phenotypic resources now available for the VRC and other Caribbean-origin vervets enable their use for genetic investigation of traits relevant to human diseases.

View Article: PubMed Central - PubMed

Affiliation: Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, CA, 90095, USA.

ABSTRACT

Background: We report here the first genome-wide high-resolution polymorphism resource for non-human primate (NHP) association and linkage studies, constructed for the Caribbean-origin vervet monkey, or African green monkey (Chlorocebus aethiops sabaeus), one of the most widely used NHPs in biomedical research. We generated this resource by whole genome sequencing (WGS) of monkeys from the Vervet Research Colony (VRC), an NIH-supported research resource for which extensive phenotypic data are available.

Results: We identified genome-wide single nucleotide polymorphisms (SNPs) by WGS of 721 members of an extended pedigree from the VRC. From high-depth WGS data we identified more than 4 million polymorphic unequivocal segregating sites; by pruning these SNPs based on heterozygosity, quality control filters, and the degree of linkage disequilibrium (LD) between SNPs, we constructed genome-wide panels suitable for genetic association (about 500,000 SNPs) and linkage analysis (about 150,000 SNPs). To further enhance the utility of these resources for linkage analysis, we used a further pruned subset of the linkage panel to generate multipoint identity by descent matrices.

Conclusions: The genetic and phenotypic resources now available for the VRC and other Caribbean-origin vervets enable their use for genetic investigation of traits relevant to human diseases.

No MeSH data available.