Indel calling....

Insertion and deletion (indel) are common class of mutations in the human genome. 

As per Human Gene Mutation Database (HGMD), indels are associated with at least 22% human diseases.

Indel is linked to human genetic diseases and cancer (cystic fibrosis, fragile X syndrome, Bloom syndrome, Huntington disease, acute myeloid leukemia, lung cancer etc.). They are common mechanism of kinase activation in cancer. 

Insertion of transposable elements such as Alu, L1, and SVA can interrupt gene function and cause diseases like hemophilia, neurofibromatosis, muscular dystrophy, and cancer.

On the other hand, deletions in the CFTR gene have been found to cause cystic fibrosis.

Serial replication slippage model explains the simple deletions and tandem duplications, leading to gene rearrangements.

Indel can occur in coding or non-coding region. The indel can be in-frame or frameshift. Frameshift indels can lead to premature stop codons. Indels can also change gene expression by altering phasing and spacing of DNA sequences in the promoter regions. A small insertion of 5 bps can rotate the binding site to the opposite face of the DNA helix, whereas a long insertion of 100 bps can increase the spacing between two binding sites. Studies have shown that in the human body, 16 to 25 % of all sequence polymorphisms are indels. Yet, a high percentage of known indels still remain undetected.

So, indel discovery and characterization in the exonic regions is important.


In that objective, popular tools include

Read mappers: BFAST, Bowtie2, BWA, Novoalign, SHRIMP

Indel callers Dindel, FreeBayes, SNVer, GATK Unified Genotyper, VarScan, SAMtools, GATK

HaplotypeCaller, and Platypus.

Bayesian probabilistic model (Dindel, GATK Unified Genotyper, SAMtools )

Heuristic model (VarScan)

Alignment-based methods map the reads to the reference sequence using read mapping software such as BWA and Novoalign. Then the mappers call indels using the alignment data following filtering steps. “True Call” refers to the indels that passed after the filters.