An initial map of insertion and deletion (INDEL) variation in the human genome

Abstract

Although many studies have been conducted to identify single nucleotide polymorphisms (SNPs) in humans, few studies have been conducted to identify alternative forms of natural genetic variation, such as insertion and deletion (INDEL) polymorphisms. In this report, we describe an initial map of human INDEL variation that contains 415,436 unique INDEL polymorphisms. These INDELs were identified with a computational approach using DNA re-sequencing traces that originally were generated for SNP discovery projects. They range from 1 bp to 9989 bp in length and are split almost equally between insertions and deletions, relative to the chimpanzee genome sequence. Five major classes of INDELs were identified, including (1) insertions and deletions of single-base pairs, (2) monomeric base pair expansions, (3) multi-base pair expansions of 2-15 bp repeat units, (4) transposon insertions, and (5) INDELs containing random DNA sequences. Our INDELs are distributed throughout the human genome with an average density of one INDEL per 7.2 kb of DNA. Variation hotspots were identified with up to 48-fold regional increases in INDEL and/or SNP variation compared with the chromosomal averages for the same chromosomes. Over 148,000 INDELs (35.7%) were identified within known genes, and 5542 of these INDELs were located in the promoters and exons of genes, where gene function would be expected to be influenced the greatest. All INDELs in this study have been deposited into dbSNP and have been integrated into maps of human genetic variation that are available to the research community.

The discovery of human genetic variations and their use as disease markers: past, present and future

“…51,52 Similarly, no large-scale attempt was made to identify indels until 2006, in which a study found several hundreds of thousands of indels in the human genome. 7 The commonness of LOHs or homozygosity regions in the genomes of outbred populations was also under appreciated until the first report appeared in 2006. 2 However, the richness of genetic variations in the human genome has recently been further corroborated by the several whole genome resequencing studies, revealing plenty of new SNPs, indels, CNVs and other structural variations.…”

“…However, no large-scale attempt was made to identify indels until 2006, in which a study identified 415 436 indels with about equal numbers of insertions and deletions. 7 The sizes of these indels ranged from 1 bp to B10 kb (which span the '1 kb boundary'), thus suggesting that the dataset is actually a mixture of indels and CNVs. In addition, the study also found over 148 000 indels located within known genes and several thousands of them are found in the promoter regions and exons of genes.…”

“…It has added much information and deepened our knowledge and understanding of the complexity and diversity of genetic variations in the human genome. In addition to the physical mapping of different types of genetic variations, such as RFLPs in the 1980s, 3 tandem repeats in the 1990s, 4 and SNPs, 5,6 indels, 7 CNVs [8][9][10] and LOHs 2 after the new millennium, the data of their biological functional roles; for example, their effects on or associations with mRNA expression levels, alternative splicing processes and other molecular and regulatory processes have also been accumulating. [11][12][13][14] Furthermore, these genetic variations were also found to be associated with various human diseases, including monogenic and complex diseases.…”

MoGUL: Detecting Common Insertions and Deletions in a Population

“…To our knowledge, the only previous study that has characterize small to medium size indels in the human populations is by Mills et al [13]. They used low coverage Sanger-style reads from 36 individuals to identify indels via the split-read mapping approach.…”

“…Remarkably, MoGUL was able to identify 83% of the indels > 50bp (20/24) that were previously detected by MoDIL, while identifying several additional variants that were missed by MoDIL, Table 1. Comparison between indel calls in chromosome 20 located by our approach with the datasets generated by Mills et al [13] (all MoGUL indels), and MoDIL [10] (only indels in NA18507, the same individual as was studied by Lee et al, was considered). For the simulation experiments we consider the indel call is correct if the difference between the true indel size and the predicted one is less than 10bp and the log likelihood ratio is greater than 10. possibly due to low coverage in the NA18507 individual specifically.…”