An Evaluation of De Novo Indels Regions of Human Genome

Background. De novo mutations are the source of all evolutionary adaptations and heritable diseases, therefore characteriztng their properties and the rate at which they arise is of fundamental importance in studies of human genome evolution. Due to technical limitations decades of mutation rate and properties’ analyses have focused on a relatively small number of loci using fully penetrant dominant Mendelian diseases and model organisms. However, advances in sequencing technology allow for an empirical assessments of mutation in the whole genome. Thus the aim of this intensity in the different study was using new generation whole exome sequencing data to do analysis of de novo indels in Lithuanian population.

Material and methods. The study group included 48 families - mother, father and offspring. We used SOLiD 5500 sequencing system, Lifescope and GATK version 3.5 software to detect and analyze de novo mutations in human exome. We employed an approach to filter the eftective number of genomic positions where we would be able to call de novo mutation. Functional annotation of genomic variants were pertormed using ANNOVAR including frequencies of genomic variants from 1000 Genomes project (1000G), ESP6500 project and ClinVar database. Statistical analysis was carried out in the R package, version 3.2.3

Results and conclusions. The human genome continuously evolves as a result of the mutation and selection. Our identified distribution of primary set of de novo mutations in Lithuanian popula­tion enriches current state of scientific knowledge and Lithuanian reference ge­nome database. Gathered data and results will be important for future clinical population-based studies and larger cohorts. We estimate the mutation rate of short germline indels to be 1.84*10"⁸. The bigger part of all identified indels was deletions or insertions from 1 to 4 length of nucleotide. There was no relationship between the chromosome size and number of de novo indels or density of genes in the chromosomes. The correlation between paternal (or maternal) age and the rate of germline indels is not significant.