ARS | Publication request: DISCOVERY AND MAPPING OF FUNCTIONALLY IMPORTANT SNP IN COW GENOME

Submitted to: BARC Poster Day
Publication Type: Abstract
Publication Acceptance Date: April 21, 2005
Publication Date: May 21, 2005
Citation: Matukumalli, L.K., Grefenstette, J.J., Sonstegard, T.S., Van Tassell, C.P. 2005. Discovery and mapping of functionally important snp in cow genome. BARC Poster Day. [Abstract].

Technical Abstract: Cow genome sequencing is underway at Baylor College of Medicine (BCM) sequencing center and will be completed in the next few months. A recent white paper indicated a goal to identify 100,000 SNP for use in identification and mapping of QTL regions. In September 2004, the preliminary assembly of Hereford cow (Btau_1.0), using whole genome shotgun (WGS) reads with an average of three fold coverage was released. BCM predicted 15,000 in silico SNP by comparing the Hereford preliminary assembly with traces from other breeds that are being confirmed using microarray chips. The SNP discovery efforts by the consortia are currently randomized in the assembly and are optimized only for maximizing the experimental SNP confirmation. In this study we summarize our SNP discovery optimization schema to identify among the high quality SNP in the population that has possible effects on regulating the gene function or altering the protein structure. Initially, a genome-wide scan of bovine SNP is performed. SNP validation efforts will be focused in the QTL regions and only for the SNP that can affect either regulation of gene function or protein structure. The preliminary bovine genome assembly is used as an anchor to build an assembly from the individual traces that have significant match to the assembly. Similar to the neighborhood quality standard (NQS) method, all the variations observed at poor quality bases or in poor quality neighborhoods are eliminated. To account for the SNP observed due to paralogs and related gene families, all the SNP occurring within a breed are also eliminated in this analysis. The remaining SNP then are categorized based on the assembly annotation as rSNP ¿ Regulatory SNP (promoter / enhancer elements), cSNP ¿ non-synonymous SNP (amino acid change), sSNP ¿ synonymous SNP (no amino acid change), tSNP ¿ creates a stop codon in the reading frame, iSNP ¿ Intron SNP, gSNP ¿ SNP in the intergenic region. The SNP discovery efforts are further focused to identify SNP implicated in the previously known QTL regions to identify the QTN candidates among the rSNP/tSNP/cSNP. These predicted SNP are then experimentally tested in the Beltsville Agricultural Research Center (BARC) Dairy Cattle Diversity Panel to verify the predicted SNP and then can be used to fine map QTL regions. We have applied this methodology so far to identify and confirm SNP in neutrophil genes that were differentially expressed at parturition