Assessing Autosomal InDel Loci With Multiple Insertions or Deletions of Random DNA Sequences in Human Genome

Abstract

Multiple mutational events of insertion/deletion occurring at or around InDel sites could form multi-allelic InDels and multi-InDels (abbreviated as MM-InDels), while InDels with random DNA sequences could imply a unique mutation event at these loci. In this study, preliminary investigation of MM-InDels with random sequences was conducted using high-throughput phased data from the 1000 Genomes Project. A total of 3,599 multi-allelic InDels and 6,375 multi-InDels were filtered with multiple alleles. A vast majority of the obtained MM-InDels (85.59%) presented 3 alleles, which implies that only one secondary insertion or deletion mutation event occurred at these loci. The more frequent presence of two adjacent InDel loci was observed within 20 bp. MM-InDels with random sequences presented an uneven distribution across the genome and showed a correlation with InDels, SNPs, recombination rate, and GC content. The average allelic frequencies and prevalence of multi-allelic InDels and multi-InDels presented similar distribution patterns in different populations. Altogether, MM-InDels with random sequences can provide useful information for population resolution.

Development of a 39 MM‐InDel multiplex assay for the forensic application

“…However, the distribution patterns of MM-InDel revealed their similar-ity in the human genome. It should be noted, however, that the presence of the additional alleles in MM-InDels was contingent upon the sequential occurrence of secondary mutational events during migration and expansion of the population [10]. Therefore, simultaneous utilization of both MM-InDels can considerably augment the number of candidate markers and provide higher efficiency for a multiplex assay.…”

“…Consequently, MM‐InDels recognized for their high polymorphism across diverse populations were deliberately chosen. Moreover, the previous study has shown that there was a more frequent presence of adjacent InDel loci within a short distance of 20 bp, which indicates a potentially strong correlation between two InDels with an interval of less than 20 bp [10]. The first insertion or deletion mutation can be regarded as an important factor for the initiation of the secondary mutation event leading to the formation of such multi‐InDels.…”

“…Consequently, multi-allelic InDel and multi-InDel markers have been introduced to address this limitation with enhanced polymorphism [8,9]. Multi-allelic InDel markers are characterized by the presence of multiple alleles originating from potential secondary mutations at a single locus [10]. Additionally, a secondary mutation with an insertion or deletion mutational event could also occur adjacent to the original InDel marker, which generates a small contiguous InDel block and is referred to as multi-InDel markers [8].…”

“…Due to the founder effect and low mutation rate of InDel markers, there might be a large difference in allele frequencies of InDels among populations [10][11][12]. Hence, the exploration of efficient InDel markers regardless of population is still a current effort in forensic genetics.…”

“…Additionally, a secondary mutation with an insertion or deletion mutational event could also occur adjacent to the original InDel marker, which generates a small contiguous InDel block and is referred to as multi‐InDel markers [8]. It has been observed in our previous study that there is a more frequent presence of adjacent InDel loci within a short distance of 20 bp, which might indicate a potential relationship in the formation of small contiguous InDel block [10].…”