Abstract
BackgroundThe identification of disease-associated genes using single nucleotide polymorphisms (SNPs) has been increasingly reported. In particular, the Affymetrix Mapping 10 K SNP microarray platform uses one PCR primer to amplify the DNA samples and determine the genotype of more than 10,000 SNPs in the human genome. This provides the opportunity for large scale, rapid and cost-effective genotyping assays for linkage analysis. However, the analysis of such datasets is nontrivial because of the large number of markers, and visualizing the linkage scores in the context of genome maps remains less automated using the current linkage analysis software packages. For example, the haplotyping results are commonly represented in the text format.ResultsHere we report the development of a novel software tool called CompareLinkage for automated formatting of the Affymetrix Mapping 10 K genotype data into the "Linkage" format and the subsequent analysis with multi-point linkage software programs such as Merlin and Allegro. The new software has the ability to visualize the results for all these programs in dChip in the context of genome annotations and cytoband information. In addition we implemented a variant of the Lander-Green algorithm in the dChipLinkage module of dChip software (V1.3) to perform parametric linkage analysis and haplotyping of SNP array data. These functions are integrated with the existing modules of dChip to visualize SNP genotype data together with LOD score curves. We have analyzed three families with recessive and dominant diseases using the new software programs and the comparison results are presented and discussed.ConclusionsThe CompareLinkage and dChipLinkage software packages are freely available. They provide the visualization tools for high-density oligonucleotide SNP array data, as well as the automated functions for formatting SNP array data for the linkage analysis programs Merlin and Allegro and calling these programs for linkage analysis. The results can be visualized in dChip in the context of genes and cytobands. In addition, a variant of the Lander-Green algorithm is provided that allows parametric linkage analysis and haplotyping.
Highlights
The identification of disease-associated genes using single nucleotide polymorphisms (SNPs) has been increasingly reported
The oligonucleotide Mapping 10 K arrays [1] have been used for linkage analysis [2,3,4] and their advantages in genome coverage and information content compared to microsatellite-based assays has been demonstrated
We report the development of a new software tool called CompareLinkage that can be used for automated conversion of Mapping 10 K genotype data into the "Linkage" format for linkage analysis in Merlin, GeneHunter and Allegro [8]
Summary
The identification of disease-associated genes using single nucleotide polymorphisms (SNPs) has been increasingly reported. The Affymetrix Mapping 10 K SNP microarray platform uses one PCR primer to amplify the DNA samples and determine the genotype of more than 10,000 SNPs in the human genome This provides the opportunity for large scale, rapid and cost-effective genotyping assays for linkage analysis. The haplotyping results are represented commonly in a text format without any gene context. After performing the linkage analysis using one or more of these programs, the CompareLinkage software can export the linkage score information into the dChip software [9,10,11] to visualize the results within a chromosome window. The linkage score curves, genotypes and haplotypes are graphically displayed in a dChip chromosome window which has the genes, cytoband and SNP marker information included. Together the CompareLinkage and dChip software programs provide for the first time a graphical user interface (GUI) and an automated procedure for comparative linkage analysis utilizing three commonly used linkage software programs
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