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

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，以确定随机分布在恒河猴（Macaca mulatta）基因组中的约83，333个单核苷酸多态性（SNP）。将对从7个不同区域人群的合并（n=25）DNA样本构建的简化代表文库（RRL）中的每个DNA片段的至少10个拷贝进行测序，然后过滤、解析并与恒河猴草图序列进行比较，并使用我们先前开发的生物信息学工具相互比较，以确定83，333个SNP的位置、侧翼序列和次要等位基因频率（MAF）。将在Iliumina iSelect芯片上构建7，600个SNP的基因分型试验，这些SNP在印度和中国恒河猴之间的频率差异最大，并在192只印度恒河猴、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。7，600个SNPs的基因型将用于1）证实多代家系中SNPs的孟德尔分离，2）评估SNPs准确估计印度/中国杂交、纯种动物中印度和中国血统比例的能力，3）鉴定用于QTL混合作图的血统信息标记，并进行“气质”QTL的混合作图。".我们的SNP地图将通过包括dbSNP在内的几个渠道提供。将在来自6个不同长尾猕猴种群的96个样本中对长尾猕猴的83，333个SNP中的384个最有可能提供信息的SNP进行基因分型，以确定最少96个SNP组，每个SNP组用于识别原产国和亲子关系分析以及用于遗传管理的估计参数。检测将由这两个小组组成，并提供给NIH研究人员，以收回成本。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。

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.