Common deletions and SNPs are in linkage disequilibrium in the human genome

Abstract

Humans show great variation in phenotypic traits such as height, eye color and susceptibility to disease. Genomic DNA sequence differences among individuals are responsible for the inherited components of these complex traits. Reports suggest that intermediate and large-scale DNA copy number and structural variations are prevalent enough to be an important source of genetic variation between individuals. Because association studies to identify genomic loci associated with particular phenotypic traits have focused primarily on genotyping SNPs, it is important to determine whether common structural polymorphisms are in linkage disequilibrium with common SNPs, and thus can be assessed indirectly in SNP-based studies. Here we examine 100 deletion polymorphisms ranging from 70 bp to 7 kb. We show that common deletions and SNPs ascertained with similar criteria have essentially the same distribution of linkage disequilibrium with surrounding SNPs, indicating that these polymorphisms may share evolutionary history and that most deletion polymorphisms are effectively assayed by proxy in SNP-based association studies.

Population structure in copy number variation and SNPs in the CCL4L chemokine gene

“…However, it is important to determine whether CNVs are in LD with common SNPs, and thus if CNV could be assessed indirectly in SNP-based studies. Regarding this question, although it has been shown that small indels and surrounding SNPs are in LD in the human genome, 30 Redon et al 4 found that diploid copy number of multi-allelic CNVs is poorly predicted by neighboring SNPs. Interestingly, among the populations included in this study the L1/L2 variants (located inside the CNV) have a high correlation with the CCL4L copy number, and, therefore, these variants could be used as a proxy of CCL4L copies of a given population.…”

Characterizing linkage disequilibrium and evaluating imputation power of human genomic insertion-deletion polymorphisms

“…As common indels and SNP variants were previously found to have similar LD profiles [26,31], we predicted that low frequency indels and SNPs would also be similar. We found indel-SNP LD was primarily with frequency matched SNPs - that is, low frequency indels were found to be in LD with low frequency SNPs but not common SNPs (Figure 2b).…”

“…Although SNPs and indels arise by different mechanisms in DNA replication or repair, previous studies using only common indels and SNP variants found that these polymorphisms had similar LD profiles, thus implying a shared evolutionary history [27,31]. Using the larger dataset provided by 1000G that includes both common and low frequency variants, we compared the LD properties between pairwise indel-SNP and SNP-SNP.…”

Gene expression changes in normal haematopoietic cells

“…Current genomic technologies have the capacity to examine millions of single nucleotide polymorphisms (SNPs) and acquired mutations using relatively little starting material, 77,78 and these assays have already been found to be extremely useful for identifying nucleotide changes, uniparental disomy (UDP), and loss of heterogeneity (LOH) in both normal and diseased states. 79 As this technology evolves, arraybased SNP and comparative genomic hybridization platforms will enable researcher to study the genetic variability in hematopoietic cells with increasing precision and genomic coverage.…”