Familial long-read sequencing increases yield of de novo mutations.

ABSTRACT: Studies of de novo mutation (DNM) have typically excluded some of the most repetitive and complex regions of the genome because these regions cannot be unambiguously mapped with short-read sequencing data. To better understand the genome-wide pattern of DNM, we generated long-read sequence data from an autism parent-child quad with an affected female where no pathogenic variant had been discovered in short-read Illumina sequence data. We deeply sequenced all four individuals by using three sequencing platforms (Illumina, Oxford Nanopore, and Pacific Biosciences) and three complementary technologies (Strand-seq, optical mapping, and 10X Genomics). Using long-read sequencing, we initially discovered and validated 171 DNMs across two children-a 20% increase in the number of de novo single-nuc

SUBMITTER: Noyes MD 

PROVIDER: S-EPMC9069071 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature