Non-invasive prenatal testing as a valuable source of population specific allelic frequencies

Abstract

We declare potential competing financial interest in the form of employee contracts (see affiliations for each author) with Geneton Ltd. that participated in the development of a commercial NIPT test in Slovakia. On the other hand, Geneton Ltd. is not a provider of this commercial test, but still continues to do basic and applied research in the field of NIPT.Minarik G and Sekelska M are employees of Medirex Inc./TrisomyTest Ltd. (the commercial providers of NIPT testing in Slovakia), their participation in the study was, however, limited to the routine NIPT testing that generated the genomic results reused in our study. The other authors declare no possible competing interests.

Genetic profiling of Vietnamese population from large-scale genomic analysis of non-invasive prenatal testing data

“…Although the 112 sequencing depth per sample was low, there might be more than one read from the same 113 sample overlapping at a genome position. This problem may affect the estimation of allele 114 frequency because the estimation is based on the assumption that a sample may contribute 115 only 0 or 1 allele (read) at any given genome position [12,13]. For instance, we found that the 116 average percentage of genome positions with depth 2x (i.e.…”

“…At any genome position, there were on average 47 out of 119 2,683 samples that each contributed two reads (Supplementary Figure S3). To address this 120 problem, we followed a filtering strategy from previous studies [12,13] to keep only one read if 121 there were overlapping reads in a sample. Thus, for every genome position, each sample could 122…”

“…An alternative approach has been proposed recently to re-use the low-coverage genome 61 sequencing data from non-invasive prenatal testing (NIPT) for large-scale population genetics 62 studies [12,13]. NIPT is a method that sequences cell-free DNA from maternal plasma at an 63 ultra-low depth of 0.1-0.2x to detect fetal aneuploidy [14].…”

“…In this paper, we presented the first study of Vietnamese genetic variations from non-invasive 78 prenatal testing data, and to the best of our knowledge, the third of such kinds in the world 79 [12,13]. We analyzed the NIPT data of 2,683 pregnant Vietnamese women to identify genetic 80 variants and their allele frequency distribution in the Vietnamese population.…”

“…First, currently there is no 234 variant calling tool that is designed specifically for NIPT data. Here we used Mutect2 and 235 previous studies also used similar somatic calling tools with the purpose of identifying all 236 possible variants at a genome site [12,13]. Thus, we took a conservative approach to consider 237 only SNPs but not indels to ensure a reliable call set.…”