Achievements

Accurate identification and phasing of variants are paramount for the detection of pathological genetic diseases and precision medicine. Long-read sequencing is significantly more powerful than conventional short-read sequencing in terms of its ability to detect structural variants, complex variant calling, and variant phasing. SNP phasing and sequencing of difficult regions, such as repeats and structural variants of clinical significance, are critical in newborn genetic screening. We used Illumina Complete Long Read (ICLR) to sequence DNA from fresh Blood samples and compared it with data obtained from Dry Blood Spots (DBS). We also studied the effect of down-sampling on variant identification in ICLR. Sequencing libraries were prepared following the manufacturer’s protocol and sequenced on the NovaSeq 6000 platform. The sequencing data was analyzed on the DRAGEN ICLR WGS App on the BaseSpace Sequence Hub. Sequencing metrics substitution rate, median coverage, insert size, N50 value, percentage biallelic variants, and phased heterozygous SNVs were analyzed. Additionally, the number of SNPs, nonSNPs, and structural variants obtained from ICLR was compared with PacBio SMRTTM sequencing and Illumina SNP array. The results of this study show that ICLR sequencing precision reads can provide high sensitivity for newborn genetic screening