Long-read sequencing (LRS) promises to improve characterization of structural variants (SVs), a major source of genetic diversity. We generated LRS data on 3,622 Icelanders using Oxford Nanopore Technologies, and identified a median of 22,636 SVs per individual (a median of 13,353 insertions and 9,474 deletions), spanning a median of 10 Mb per haploid genome. We discovered a set of 133,886 reliably genotyped SV alleles and imputed them into 166,281 individuals to explore their effects on diseases and other traits. We discovered an association with a rare (AF = 0.037%) deletion of the first exon of PCSK9. Carriers of this deletion have 0.93 mmol/L (1.31 SD) lower LDL cholesterol levels than the population average (p-value = 7.0•10 −20 ). We also discovered an association with a multi-allelic SV inside a large repeat region, contained within single long reads, in an exon of ACAN. Within this repeat region we found 11 alleles that differ in the number of a 57 bp-motif repeat, and observed a linear relationship (0.016 SD per motif inserted, p = 6.2•10 −18 ) between the number of repeats carried and height. These results show that SVs can be accurately characterized at population scale using long read sequence data in a genome-wide non-targeted approach and demonstrate how SVs impact phenotypes.Human sequence diversity is partially due to structural variants 1 (SVs); genomic rearrangements affecting at least 50 bp of sequence in forms of insertions, deletions, inversions, or translocations. The number of SVs carried by each individual is less than the number of single nucleotide polymorphisms (SNPs) and short (< 50 bp) insertions and deletions (indels), but their greater size makes them more likely to have a functional role 2 , as evident by their disproportionately large impact on diseases and other traits 2,3 .Extensive characterization of three trios sequenced using several technologies 4 and an annotated set based on one sample (HG002) 5 indicate that humans carry 23-31 thousand SVs .
The breathing pattern before sternotomy is predominantly abdominal but moves to a thoracic and upper thoracic pattern postoperatively and is associated with reduced pulmonary function. Therapeutic interventions aimed at correcting the less effective upper thoracic breathing pattern should likely be implemented.
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