Natural genetic variation caused by small insertions and deletions in the human genome.

By Ryan E. Mills, William Stephen Pittard, J. Mullaney, Umar Farooq, T. Creasy, A. Mahurkar, David M Kemeza, Daniel S Strassler, Chris P. Ponting, C. Webber and 1 more. 2011

272 citations recorded by the source corpus.

Human genetic variation is expected to play a central role in personalized medicine. Yet only a fraction of the natural genetic variation that is harbored by humans has been discovered to date. Here we report almost 2 million small insertions and deletions (INDELs) that range from 1 bp to 10,000 bp in length in the genomes of 79 diverse humans. These variants include 819,363 small INDELs that map to human genes. Small INDELs frequently were found in the coding exons of these genes, and several lines of evidence indicate that such variation is a major determinant of human biological diversity. Microarray-based genotyping experiments revealed several interesting observations regarding the population genetics of small INDEL variation. For example, we found that many of our INDELs had high levels of linkage disequilibrium (LD) with both HapMap SNPs and with high-scoring SNPs from genome-wide association studies. Overall, our study indicates that small INDEL variation is likely to be a key factor underlying inherited traits and diseases in humans.

Subfields: Genetics

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

Citations in the corpus

Low concordance of multiple variant-calling pipelines: practical implications for exome and genome sequencing (2013, background): “Indeed, initial indel mapping efforts revealed upwards of 800,000 indels in a diverse population that map to known human genes, some of which can be associated with genetic disease [42,43], while recent estimates from the 1000 Genomes Project [44] suggest a 10:1 ratio of SNVs to indels in individual”
Using the Neandertal genome to study the evolution of small insertions and deletions in modern humans (2017, background): “Small indels are a common type of sequence variation among present-day humans [39].”
Protein design and variant prediction using autoregressive generative models (2021, background): “Indels make up 15 – 21% of human polymorphisms 41 – 43 , 44% of human proteins contain disordered regions longer than 30 amino acids 40,44 , and both are enriched in association with human diseases such as cystic ﬁ brosis, many cancers 45,46 , cardiovascular and neurodegenerative diseases, and…”
Neoantigens: promising targets for cancer therapy (2023, background): “These MHC-I-associated peptides (MAPs) derived from genes at non-coding regions expand the range of CD8 T cell immune surveillance from 2% (the proportion of the human genome in exons) to 75%.(52,172,174,175) According to a proteogenomic profiling of non-canonical proteins, 60% of noncanonical prote”
An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge (2014, methodology): “Other reference datasets mentioned were the Mills Indel Gold Standard [42], NCBI Cl inVar (Bethesda MD) as well as public sequencing data produced from the technologies used in this challe nge.”