Development, Management and Use of a SNP Map for Rhesus Macaque

恒河猴 SNP 图谱的开发、管理和使用

• 批准号: 8106143
• 负责人: DAVID Glenn SMITH
• 金额: $ 34.21万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-05 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8106143
• 关键词: Admixture; Aliquot; Animal Model; Animals; Applications Grants; Arts; Bioinformatics; Biological Assay; Biomedical Research; Breeding; California; Cambodia; Cataloging; Catalogs; Characteristics; China; Chinese People; Chromosomes; Code; Communities; Country; Custom; DNA; DNA Sequence; Data; Development; Disease; Disease Association; Educational workshop; Enzymes; Exhibits; Family; Frequencies; Functional RNA; Funding; Gene Frequency; Generic Drugs; Genes; Genetic; Genetic Identity; Genetic Markers; Genetic Variation; Genome; Genome Mappings; Genomics; Genotype; Geographic Locations; Grant; Haplotypes; Health; Hereditary Disease; Human; Hybrids; Inbreeding; India; Individual; Indochina; Indonesia; Java; Laboratories; Letters; Libraries; Linkage Disequilibrium; Location; Macaca; Macaca mulatta; Malaysia; Maps; Mauritius; Medical; Methodology; Methods; Minor; Modeling; National Center for Research Resources; Other Genetics; Phenotype; Philippines; Phylogenetic Analysis; Population; Population Genetics; Primates; Principal Investigator; Quantitative Trait Loci; Reading; Recovery; Research; Research Personnel; Resources; Running; Sampling; Sampling Errors; Sarawak; Services; Signal Transduction; Single Nucleotide Polymorphism; Single Nucleotide Polymorphism Map; Site; Structure; Technology; Temperament; Testing; Time; Translational Research; United States National Institutes of Health; Update; Vietnam; animal resource; base; cost; cost effective; density; disease phenotype; genetic analysis; genetic pedigree; genetic resource; genome wide association study; human disease; insight; meetings; novel; programs; public health relevance; restriction enzyme; segregation; tool; web site; working group

DESCRIPTION (provided by applicant): We will use the recently completed rhesus macaque genome map, to identify approximately 83,333 single nucleotide polymorphisms (SNPs) randomly distributed throughout the rhesus macaque (Macaca mulatta) genome. At least ten copies of each DNA fragments in reduced representation libraries (RRLs) constructed from pooled (n=25)DNA samples from 7 different regional populations will be sequenced, then filtered, parsed and compared to the rhesus macaque draft sequence and to each other using bioinformatics tools we previously developed to identify the locations, flanking sequences and minor allele frequencies (MAFs) of 83,333 SNPs. Genotyping assays on lliumina iSelect chips will be constructed for the 7,600 SNPs whose frequencies differ most between Indian and Chinese rhesus macaques and genotyped in geographically representative samples of 192 Indian rhesus macaques, and192 Chinese rhesus macaques and in 678 Indian/Chines rhesus macaques with varying proportions of Indian and Chinese ancestry. Genotypes for the 7,600 SNPs will be used to 1) confirm Mendelian segregation of SNPs in multigeneration families, 2) assess the ability of the SNPs to accurately estimate proportions of Indian and Chinese ancestry in Indian/Chinese hybrid, pedigreed animals and 3) identify ancestry informative markers for admixture mapping of QTLs and to conduct admixture mapping of a QTL for "temperament.". Our SNP map will be made publically available through several outlets including dbSNP. The 384 most potentially informative of the 83,333 SNPs for longtail macaques will be genotyped in 96 samples from six different longtail macaque populations to identify minimum panels of 96 SNPs each for identifying country of origin and for parentage analysis and estiinating parameters useful for genetic management. Assays will be constructed of these two panels and made available to NIH investigators, providing cost recovery. The genotypes of SNPs described above will be used for genomic and population structure analyses of regional populations of rhesus and longtail macaques.

描述（由申请人提供）：我们将使用最近完成的恒河猴基因组图谱，鉴定随机分布在恒河猴（Macaca mulatta）基因组中的大约83333个单核苷酸多态性（snp）。我们将对来自7个不同地区人群的25个DNA样本构建的减少表示文库（RRLs）中的每个DNA片段进行至少10个拷贝的测序，然后使用我们之前开发的生物信息学工具进行筛选、解析，并与恒河猴草图序列进行比较，以确定83333个snp的位置、侧翼序列和次要等位基因频率（maf）。利用lumina iSelect芯片对印度和中国恒河猴中频率差异最大的7600个snp进行基因分型分析，并在192只印度恒河猴和192只中国恒河猴和678只具有不同比例印度和中国血统的印度/中国恒河猴的地理代表性样本中进行基因分型。7600个snp的基因型将用于1)确认多代家族中snp的孟德尔分离，2)评估snp在印度/中国杂交、纯种动物中准确估计印度和中国血统比例的能力，3)确定用于QTL混合作图的祖先信息标记，并进行“气质”QTL的混合作图。我们的SNP地图将通过包括dbSNP在内的几个渠道公开。研究人员将对来自6个不同长尾猕猴种群的96个样本的83333个长尾猕猴snp中384个最有可能提供信息的snp进行基因分型，以确定每个snp的最少96个组，以确定原产国、亲子分析和估计遗传管理有用的参数。化验将由这两个小组组成，并提供给NIH的调查人员，以提供成本回收。上述snp的基因型将用于恒河猴和长尾猕猴区域种群的基因组和种群结构分析。

项目成果

Gene expression and TB pathogenesis in rhesus macaques: TR4, CD40, CD40L, FAS (CD95), and TNF are host genetic markers in peripheral blood mononuclear cells that are associated with severity of TB lesions.

恒河猕猴中的基因表达和TB发病机理：TR4，CD40，CD40L，FAS（CD95）和TNF是与TB病变严重程度有关的外周血单核细胞中的宿主遗传标记。

• DOI: 10.1016/j.meegid.2015.10.010
• 发表时间: 2015-12
• 期刊: INFECTION GENETICS AND EVOLUTION
• 影响因子: 3.2
• 作者: Roodgar, Morteza;Ross, Cody T.;Tarara, Ross;Lowenstine, Linda;Dandekar, Satya;Smith, David Glenn
• 通讯作者: Smith, David Glenn