Imputation of Microsatellite Markers With Tag SNPs

Abstract

Of the two most common forms of genetic variation in the human genome, Single Nucleotide Polymorphisms (SNPs) and Variable Number Tandem Repeat Polymorphisms (VNTRs), SNPs are much more easily and inexpensively assayed in a high-throughput manner. For this reason, we seek to explore methods that can allow us to use the more readily available SNP genotype information to infer VNTR genotypes in nearby genomic regions. We focus in particular on imputing a VNTR polymorphism, 5-HTTLPR, in the promoter region of the serotonin transporter gene in a small sample of individuals from an ongoing neuroimaging genetics study, a portion of whom have both manual 5-HTTLPR genotypes and genome wide SNP data. We investigate four imputation methods: Tagger, Vertex Discriminant Analysis (VDA), IMPUTE2, and BEAGLE. We achieve an accuracy of 93% with VDA in our subsample of Caucasians with manual 5-HTTLPR genotypes. Further, we find that for the entire Caucasian subsample without manual genotypes, a majority of the imputation methods tested make the same 5-HTTLPR genotype call.