Genome structural variation discovery and genotyping

By Can Alkan, Bradley P. Coe, Evan E. Eichler. Nature reviews genetics, 2011

1,575 citations recorded by the source corpus.

Comparisons of human genomes show that more base pairs are altered as a result of structural variation — including copy number variation — than as a result of point mutations. Here we review advances and challenges in the discovery and genotyping of structural variation. The recent application of massively parallel sequencing methods has complemented microarray-based methods and has led to an exponential increase in the discovery of smaller structural-variation events. Some global discovery biases remain, but the integration of experimental and computational approaches is proving fruitful for accurate characterization of the copy, content and structure of variable regions. We argue that the long-term goal should be routine, cost-effective and high quality de novo assembly of human genomes to comprehensively assess all classes of structural variation.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a70a05dc860131ee8c3aea8ef220651de00c0803

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Citations in the corpus

SpeedSeq: Ultra-fast personal genome analysis and interpretation (2014, background): “First, for various technical reasons, SV is recognized to be by far the most difficult form of variation to detect reliably[25].”
Contiguous and accurate de novo assembly of metazoan genomes with modest long read coverage (2015, neutral): “However, as a result of the cost effectiveness and concomitant popularity of short read technologies, the average quality and contiguity of published genomes has plummeted (36).”
Characterization of ancient and modern genomes by SNP detection and phylogenomic and metagenomic analysis using PALEOMIX (2014, neutral): “The impact of this technology is vast, with many applications in biosciences, including genome-wide SNP 3 and copy number variation (CNV) 4 discovery, nucleosome mapping 5 and genome-wide methylation profiling 6 , genome re-sequencing 7 and de novo genome assembly 8 .”
Computational tools for copy number variation (CNV) detection using next-generation sequencing data: features and perspectives (2013, background): “The advantages of the NGS approach also include higher coverage and resolution, more accurate estimation of copy numbers, more precise detection of breakpoints, and higher capability to identify novel CNVs [1,14].”
Special features of RAD Sequencing data: implications for genotyping (2012, background): “For example, handling low depth or repeat loci are issues widely discussed elsewhere in the literature (DePristo et al. 2011; Nielsen et al. 2011), and missing alleles will also occur with structural variation (Alkan et al. 2011).”
Exome sequencing as a tool for Mendelian disease gene discovery (2011, neutral): “…are maturing 80 , there is considerable room for improvement in detecting small insertion–deletions and especially copy number changes from short-read exome sequence data 81 (for example, detecting a heterozygous, single-exon deletion with breakpoints that fall within adjacent introns).”
LUMPY: a probabilistic framework for structural variant discovery (2012, background): “spanning paired-end reads that align discordantly relative to each other (read-pair), and breakpoint-containing single reads that align in split fashion to discontiguous loci in the reference genome (split-read) [1,2].”
Computational pan-genomics: status, promises and challenges (2016, methodology): “Despite efforts to capture structural variation based on discordant mapping of short reads, a major fraction remains undetected in large part because of their complexity and owing to the incompleteness of the current reference genome [59, 60].”
Comprehensive evaluation of structural variation detection algorithms for whole genome sequencing (2019, methodology): “Sequencing-based methods take several conceptual approaches to derive information about SVs from short read sequencing data [2, 9, 16 – 18].”
Accurate detection of complex structural variations using single molecule sequencing (2017, neutral): “Copy number variations are observed as decreases (deletions) or increases (amplifications) in aligned read coverage 12 , and other types of SVs are identified by the arrangement of paired-end reads or split-read alignments 13–16 .”
Structural variant calling: the long and the short of it (2019, background): “1), and the alterations between the two can be systematically identified: the comparison of each position in one genome to its corresponding position in the other genome should allow the identification of all forms of variations [3, 73].”
Nonhybrid, finished microbial genome assemblies from long-read SMRT sequencing data (2013, background): “Sanger sequencing of BAC libraries is the preferred approach to resolve genomic regions with high repeat content and structural variation in complex genomes, including the human genome 23–25 .”