Detection and interpretation of genomic structural variation in mammals.

  title={Detection and interpretation of genomic structural variation in mammals.},
  author={Ira M. Hall and Aaron R. Quinlan},
  journal={Methods in molecular biology},
Structural variation (SV) encompasses diverse types of genomic variants including deletions, duplications, inversions, transpositions, translocations, and complex rearrangements, and is now recognized to be an abundant class of genetic variation in mammals. Different individuals, or strains, of a given species can differ by thousands of variants. However, despite a large number of studies over the past decade and impressive progress on many fronts, there remain significant gaps in our knowledge… 

Human copy number variants are enriched in regions of low mappability

PopSV, a CNV caller that relies on multiple samples to control for technical variation, is used to identify 3455 regions with recurrent CNVs that were missing from existing catalogs and identifies 347 genes with a novel exonic CNV in low-mappability regions.

Population-based approaches to characterize copy number variation from whole-genome sequencing in healthy individuals and disease cohorts

A different approach that uses a large set of reference samples to correct for technical variation and was found to be more sensitive than other methods for CNV detection and to investigate copy number variation in low-mappability regions.

Human copy number variants are enriched in regions of low-mappability

The results provide the most exhaustive map of CNVs across the human genome to date and demonstrate the broad functional impact of this type of genetic variation including in regions of low-mappability.

A Streamlined Method for Detecting Structural Variants in Cancer Genomes by Short Read Paired-End Sequencing

This study describes a method to efficiently identify large tumor-specific deletions, inversions, duplications and translocations from low coverage data using SVDetect or BreakDancer software and a set of novel filtering procedures designed to reduce false positive calls.

Analysis and Annotation of Whole‐Genome or Whole‐Exome Sequencing Derived Variants for Clinical Diagnosis

  • E. Worthey
  • Biology
    Current protocols in human genetics
  • 2017
This unit provides an overview of specific challenges related to implementation of genome‐wide sequencing in a clinical setting given the dramatic increase in dataset size and complexity.

Global characterization of copy number variants in epilepsy patients from whole genome sequencing

This genome-wide survey of copy number variants of epilepsy patients revealed an enrichment of rare exonic events in epilepsy patients, especially in genes with predicted loss-of-function intolerance, suggesting that comprehensive sequence-based profiling of CNVs could help explain a larger fraction of epilepsy cases.

Tumor subclone structure reconstruction with genomic variation data

This dissertation presents a computational framework that examines somatic variation events, such as copy number changes, loss of heterozygosity, or point mutations, in order to identify the underlying subclone structure, and shows that the method can be valuable in prioritizing variants for function study.

Genome-wide characterization of copy number variants in epilepsy patients

An enrichment of rare exonic events in epilepsy patients is found, especially in genes with predicted loss-of-function intolerance and in regions associated with changes in the gene expression, such as expression QTLs or DNase I hypersensitive sites.

Detection of Structural Variants by NGS: Revealing Missing Alleles in Lysosomal Storage Diseases

The current knowledge about the most recurrent and private SVs involving LSDs-related genes are summarized, advantages and drawbacks related to the use of the NGS in the SVs detection are reviewed, and the challenges to bring this type of analysis in clinical diagnostics are discussed.

Genome Fusion Detection: a novel method to detect fusion genes from SNP-array data

This work presents a novel method, the Genomic Fusion Detection algorithm, to predict fusion genes on a genomic level based on SNP-array data, which detects genes at the transition region of segments with copy number variation.



Genome-wide mapping and assembly of structural variant breakpoints in the mouse genome.

An algorithm to localize SV breakpoints by paired-end mapping, and a general approach for the genome-wide assembly and interpretation of breakpoint sequences are developed, which demonstrate that HYDRA accurately maps diverse classes of SV, including those involving repetitive elements such as transposons and segmental duplications.

Mapping and sequencing of structural variation from eight human genomes

This work employs a clone-based method to interrogate intermediate structural variation in eight individuals of diverse geographic ancestry and provides the first high-resolution sequence map of human structural variation—a standard for genotyping platforms and a prelude to future individual genome sequencing projects.

Paired-End Mapping Reveals Extensive Structural Variation in the Human Genome

High-throughput and massive paired-end mapping (PEM) was used to map SVs in an African and in a putatively European individual and identified shared and divergent SVs relative to the reference genome, documenting that the number of SVs among humans is much larger than initially hypothesized; many of the SVs potentially affect gene function.

Recurrent DNA inversion rearrangements in the human genome

A PCR-based approach was used to identify breakpoint regions of rearranged structures in the human genome that are located in reverse orientation, which may lead to chromosomal inversions and indicate that recurrent genomic rearrangements occur at relatively high frequency in somatic cells.

The genomic architecture of segmental duplications and associated copy number variants in dogs.

The first systematic and genome-wide analysis of segmental duplications and associated copy number variants (CNVs) in the modern domesticated dog, Canis familiaris, is described, providing insight into mechanisms of canine genome evolution and generating a valuable resource for future evolutionary and phenotypic studies.

The origins and impact of primate segmental duplications.

Hotspots of mammalian chromosomal evolution

This analysis supports a nonrandom model of chromosomal evolution that implicates specific regions within the mammalian genome as having been predisposed to both recurrent small-scale duplication and large-scale evolutionary rearrangements.

Mouse segmental duplication and copy number variation

The authors' data suggest that different mouse strains show comparable, if not greater, copy number polymorphism when compared to human; however, such variation is more locally restricted.

Extensive variation between inbred mouse strains due to endogenous L1 retrotransposition.

Recent endogenous L1 retrotransposition has diversified genomic structures and transcripts extensively, distinguishing mouse lineages and driving a major portion of natural genetic variation.

Mobile elements create structural variation: analysis of a complete human genome.

This study presents the first comprehensive analysis of mobile element-related structural variants in the complete DNA sequence of an individual and demonstrates that mobile elements play an important role in generating inter-individual structural variation.