Long-read sequencing and structural variant characterization in 1,019 samples from the 1000 Genomes Project.

Structural variants (SVs) contribute significantly to human genetic diversity and disease . Previously, SVs have remained incompletely resolved by population genomics, with short-read sequencing facing limitations in capturing the whole spectrum of SVs at nucleotide resolution . Here we leveraged nanopore sequencing to construct an intermediate coverage resource of 1,019 long-read genomes sampled within 26 human populations from the 1000 Genomes Project.

Structural and genetic diversity in the secreted mucins, and .

The secreted mucins MUC5AC and MUC5B play critical defensive roles in airway pathogen entrapment and mucociliary clearance by encoding large glycoproteins with variable number tandem repeats (VNTRs). These polymorphic and degenerate protein coding VNTRs make the loci difficult to investigate with short reads. We characterize the structural diversity of and by long-read sequencing and assembly of 206 human and 20 nonhuman primate (NHP) haplotypes.

A multilocus approach for accurate variant calling in low-copy repeats using whole-genome sequencing.

Motivation: Low-copy repeats (LCRs) or segmental duplications are long segments of duplicated DNA that cover > 5% of the human genome. Existing tools for variant calling using short reads exhibit low accuracy in LCRs due to ambiguity in read mapping and extensive copy number variation. Variants in more than 150 genes overlapping LCRs are associated with risk for human diseases.

Robust and accurate estimation of paralog-specific copy number for duplicated genes using whole-genome sequencing.

The human genome contains hundreds of low-copy repeats (LCRs) that are challenging to analyze using short-read sequencing technologies due to extensive copy number variation and ambiguity in read mapping. Copy number and sequence variants in more than 150 duplicated genes that overlap LCRs have been implicated in monogenic and complex human diseases. We describe a computational tool, Parascopy, for estimating the aggregate and paralog-specific copy number of duplicated genes using whole-genome sequencing (WGS).

Sensitive alignment using paralogous sequence variants improves long-read mapping and variant calling in segmental duplications.

The ability to characterize repetitive regions of the human genome is limited by the read lengths of short-read sequencing technologies. Although long-read sequencing technologies such as Pacific Biosciences (PacBio) and Oxford Nanopore Technologies can potentially overcome this limitation, long segmental duplications with high sequence identity pose challenges for long-read mapping. We describe a probabilistic method, DuploMap, designed to improve the accuracy of long-read mapping in segmental duplications.

Targeted sequencing reveals complex, phenotype-correlated genotypes in cystic fibrosis.

Background: Cystic fibrosis (CF) is one of the most common life-threatening genetic disorders. Around 2000 variants in the CFTR gene have been identified, with some proportion known to be pathogenic and 300 disease-causing mutations have been characterized in detail by CFTR2 database, which complicates its analysis with conventional methods.

Methods: We conducted next-generation sequencing (NGS) in a cohort of 89 adult patients negative for p.