Common deletion polymorphisms in the human genome


The locations and properties of common deletion variants in the human genome are largely unknown. We describe a systematic method for using dense SNP genotype data to discover deletions and its application to data from the International HapMap Consortium to characterize and catalogue segregating deletion variants across the human genome. We identified 541 deletion variants (94% novel) ranging from 1 kb to 745 kb in size; 278 of these variants were observed in multiple, unrelated individuals, 120 in the homozygous state. The coding exons of ten expressed genes were found to be commonly deleted, including multiple genes with roles in sex steroid metabolism, olfaction and drug response. These common deletion polymorphisms typically represent ancestral mutations that are in linkage disequilibrium with nearby SNPs, meaning that their association to disease can often be evaluated in the course of SNP-based whole-genome association studies.

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Figure 1: Using SNP genotypes to discover segregating deletion variants.
Figure 2: Spatially patterned aberrations in SNP genotypes.
Figure 3: Experimental validation of segregating deletions.
Figure 4: Variation in gene expression due to gene copy number variation.
Figure 5: LD of deletion polymorphisms with SNPs.


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The authors wish to thank J. Moore and L. Ziaugra for contributing their expertise on the behavior of genotyping platforms and C. Patil, J. Melo and E. Lander for commenting on manuscript drafts. We thank G. Thorisson and A. Vernon-Smith for extensive help with data coordination, and D. Conrad, J. Pritchard and K. Frazer for exchanging manuscripts before publication.

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Correspondence to David M Altshuler.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Physical clustering of patterns of apparent mendelian inconsistency and null genotypes in the HapMap data. (PDF 119 kb)

Supplementary Fig. 2

Distinct patterns of aberrant SNP genotypes caused by the same deletion polymorphisms in multiple populations. (PDF 185 kb)

Supplementary Fig. 3

Confirmation of segregating deletion variants by fluorescent in situ hybridization (FISH). (PDF 1530 kb)

Supplementary Fig. 4

Deletion variants flanked by segmental duplications. (PDF 496 kb)

Supplementary Fig. 5

Linkage disequilibrium between gene deletion polymorphisms and nearby SNPs. (PDF 317 kb)

Supplementary Table 1

Predicted deletion variants and supporting SNP evidence. (PDF 230 kb)

Supplementary Table 2

Validation of candidate deletion variants. (PDF 17 kb)

Supplementary Table 3

Gene deletion genotypes obtained by quantitative PCR for ten loci in 269 individuals. (PDF 66 kb)

Supplementary Table 4

SNP alleles that tag common gene deletion alleles, for potential use in medical genetic studies. (PDF 12 kb)

Supplementary Table 5

Primer and probe sequences used. (PDF 29 kb)

Supplementary Note (PDF 71 kb)

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