Document Detail

1 + 1 = 3: Development and validation of a SNP-based algorithm to identify genetic contributions from three distinct inbred mouse strains.
MedLine Citation:
PMID:  23204929     Owner:  NLM     Status:  MEDLINE    
State-of-the-art, genome-wide assessment of mouse genetic background uses single nucleotide polymorphism (SNP) PCR. As SNP analysis can use multiplex testing, it is amenable to high-throughput analysis and is the preferred method for shared resource facilities that offer genetic background assessment of mouse genomes. However, a typical individual SNP query yields only two alleles (A vs. B), limiting the application of this methodology to distinguishing contributions from no more than two inbred mouse strains. By contrast, simple sequence length polymorphism (SSLP) analysis yields multiple alleles but is not amenable to high-throughput testing. We sought to devise a SNP-based technique to identify donor strain origins when three distinct mouse strains potentially contribute to the genetic makeup of an individual mouse. A computational approach was used to devise a three-strain analysis (3SA) algorithm that would permit identification of three genetic backgrounds while still using a binary-output SNP platform. A panel of 15 mosaic mice with contributions from BALB/c, C57Bl/6, and DBA/2 genetic backgrounds was bred and analyzed using a genome-wide SNP panel using 1449 markers. The 3SA algorithm was applied and then validated using SSLP. The 3SA algorithm assigned 85% of 1449 SNPs as informative for the C57Bl/6, BALB/c, or DBA/2 backgrounds, respectively. Testing the panel of 15 F2 mice, the 3SA algorithm predicted donor strain origins genome-wide. Donor strain origins predicted by the 3SA algorithm correlated perfectly with results from individual SSLP markers located on five different chromosomes (n=70 tests). We have established and validated an analysis algorithm based on binary SNP data that can successfully identify the donor strain origins of chromosomal regions in mice that are bred from three distinct inbred mouse strains.
James D Gorham; Matthew S Ranson; Janebeth C Smith; Beverly J Gorham; Kristen-Ashley Muirhead
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Validation Studies    
Journal Detail:
Title:  Journal of biomolecular techniques : JBT     Volume:  23     ISSN:  1943-4731     ISO Abbreviation:  J Biomol Tech     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-03     Completed Date:  2013-04-17     Revised Date:  2013-09-06    
Medline Journal Info:
Nlm Unique ID:  100888641     Medline TA:  J Biomol Tech     Country:  United States    
Other Details:
Languages:  eng     Pagination:  136-46     Citation Subset:  IM    
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire 03756, USA.
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MeSH Terms
Genotyping Techniques*
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred DBA
Microsatellite Repeats
Multiplex Polymerase Chain Reaction
Polymorphism, Single Nucleotide*
Sequence Analysis, DNA*
Species Specificity
Grant Support

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