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Genome sequence and global sequence variation map with 5.5 million SNPs in Chinese rhesus macaque.

ABSTRACT: BACKGROUND: Rhesus macaque (Macaca mulatta) is the most widely used nonhuman primate animal in biomedical research. A global map of genetic variations in rhesus macaque is valuable for both evolutionary and functional studies. RESULTS: Using next-generation sequencing technology, we sequenced a Chinese rhesus macaque genome with 11.56-fold coverage. In total, 96% of the reference Indian macaque genome was covered by at least one read, and we identified 2.56 million homozygous and 2.94 million heterozygous SNPs. We also detected a total of 125,150 structural variations, of which 123,610 were deletions with a median length of 184 bp (ranging from 25 bp to 10 kb); 63% of these deletions were located in intergenic regions and 35% in intronic regions. We further annotated 5,187 and 962 nonsynonymous SNPs to the macaque orthologs of human disease and drug-target genes, respectively. Finally, we set up a genome-wide genetic variation database with the use of Gbrowse. CONCLUSIONS: Genome sequencing and construction of a global sequence variation map in Chinese rhesus macaque with the concomitant database provide applicable resources for evolutionary and biomedical research.

SUBMITTER: Fang X

PROVIDER: S-EPMC3218825 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Genome sequence and global sequence variation map with 5.5 million SNPs in Chinese rhesus macaque.

Fang Xiaodong X Zhang Yanfeng Y Zhang Rui R Yang Lixin L Li Ming M Ye Kaixiong K Guo Xiaosen X Wang Jun J Wang Jun J Su Bing B

Genome biology 20110706 7

<h4>Background</h4>Rhesus macaque (Macaca mulatta) is the most widely used nonhuman primate animal in biomedical research. A global map of genetic variations in rhesus macaque is valuable for both evolutionary and functional studies.<h4>Results</h4>Using next-generation sequencing technology, we sequenced a Chinese rhesus macaque genome with 11.56-fold coverage. In total, 96% of the reference Indian macaque genome was covered by at least one read, and we identified 2.56 million homozygous and 2. ...[more]

PMID: 21733155

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Project description:BackgroundUntil recently, few genomic reagents specific for non-human primate research have been available. To address this need, we have constructed a macaque-specific high-density oligonucleotide microarray by using highly fragmented low-pass sequence contigs from the rhesus genome project together with the detailed sequence and exon structure of the human genome. Using this method, we designed oligonucleotide probes to over 17,000 distinct rhesus/human gene orthologs and increased by four-fold the number of available genes relative to our first-generation expressed sequence tag (EST)-derived array.ResultsWe constructed a database containing 248,000 exon sequences from 23,000 human RefSeq genes and compared each human exon with its best matching sequence in the January 2005 version of the rhesus genome project list of 486,000 DNA contigs. Best matching rhesus exon sequences for each of the 23,000 human genes were then concatenated in the proper order and orientation to produce a rhesus "virtual transcriptome." Microarray probes were designed, one per gene, to the region closest to the 3' untranslated region (UTR) of each rhesus virtual transcript. Each probe was compared to a composite rhesus/human transcript database to test for cross-hybridization potential yielding a final probe set representing 18,296 rhesus/human gene orthologs, including transcript variants, and over 17,000 distinct genes. We hybridized mRNA from rhesus brain and spleen to both the EST- and genome-derived microarrays. Besides four-fold greater gene coverage, the genome-derived array also showed greater mean signal intensities for genes present on both arrays. Genome-derived probes showed 99.4% identity when compared to 4,767 rhesus GenBank sequence tag site (STS) sequences indicating that early stage low-pass versions of complex genomes are of sufficient quality to yield valuable functional genomic information when combined with finished genome information from a closely related species.ConclusionThe number of different genes represented on microarrays for unfinished genomes can be greatly increased by matching known gene transcript annotations from a closely related species with sequence data from the unfinished genome. Signal intensity on both EST- and genome-derived arrays was highly correlated with probe distance from the 3' UTR, information often missing from ESTs yet present in early-stage genome projects.

Dataset Information

Genome sequence and global sequence variation map with 5.5 million SNPs in Chinese rhesus macaque.

Publications

Genome sequence and global sequence variation map with 5.5 million SNPs in Chinese rhesus macaque.

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