The functional impact of structural variation in humans - PubMed (original) (raw)
Review
The functional impact of structural variation in humans
Matthew E Hurles et al. Trends Genet. 2008 May.
Abstract
Structural variation includes many different types of chromosomal rearrangement and encompasses millions of bases in every human genome. Over the past 3 years, the extent and complexity of structural variation has become better appreciated. Diverse approaches have been adopted to explore the functional impact of this class of variation. As disparate indications of the important biological consequences of genome dynamism are accumulating rapidly, we review the evidence that structural variation has an appreciable impact on cellular phenotypes, disease and human evolution.
Figures
Figure 1. Types of structural variant
Eight different types of structural variant are depicted, defined relative to the reference genome sequence
Figure 2. Influence of structural variation on gene regulation
A gene is represented by a set of exons (grey boxes), an enhancer (white box) and repressor (black box). Four general mechanisms by which a Structural Variant can impact upon gene expression are depicted. For each mechanism, an exemplar structural variant (in colour) is shown relative to the central reference gene structure.
Figure 3. Examples of evidence for selection on structural variants
(a) Selection might have favoured an APOBEC3 deletion, (b) an increase in AMY1 copy number in populations with a high starch diet (c) and an inversion polymorphism encompassing a number of genes, including MAPT and a truncated copy of NSF. The presence or absence of evidence for positive selection acting on each variant is summarised on the right hand side: an understanding of the relevant biological effect (Biol. effect), an increased number of offspring (Incr. offsp.), an unusually long haplotype (Long hap.), elevated population differentiation (Pop. Diff.), a skewed allele frequency spectrum (Freq. spec.) or an excess of functional changes (Funct. changes). A ‘-‘ indicates either that there was no evidence or that evidence was not sought.
Similar articles
- Understanding genome structural variations.
Abyzov A, Li S, Gerstein MB. Abyzov A, et al. Oncotarget. 2016 Feb 16;7(7):7370-1. doi: 10.18632/oncotarget.6485. Oncotarget. 2016. PMID: 26657727 Free PMC article. No abstract available. - An isochore map of human chromosomes.
Costantini M, Clay O, Auletta F, Bernardi G. Costantini M, et al. Genome Res. 2006 Apr;16(4):536-41. doi: 10.1101/gr.4910606. Genome Res. 2006. PMID: 16597586 Free PMC article. - Regulatory variation and evolution: implications for disease.
Dermitzakis ET. Dermitzakis ET. Adv Genet. 2008;61:295-306. doi: 10.1016/S0065-2660(07)00011-9. Adv Genet. 2008. PMID: 18282511 Review. - Gene duplication: a drive for phenotypic diversity and cause of human disease.
Conrad B, Antonarakis SE. Conrad B, et al. Annu Rev Genomics Hum Genet. 2007;8:17-35. doi: 10.1146/annurev.genom.8.021307.110233. Annu Rev Genomics Hum Genet. 2007. PMID: 17386002 Review. - What's in the "fold"?
Mehra P, Kalani A. Mehra P, et al. Life Sci. 2018 Oct 15;211:118-125. doi: 10.1016/j.lfs.2018.09.021. Epub 2018 Sep 10. Life Sci. 2018. PMID: 30213728 Review.
Cited by
- Prediction of the 3D cancer genome from whole-genome sequencing using InfoHiC.
Lee Y, Park SH, Lee H. Lee Y, et al. Mol Syst Biol. 2024 Sep 25. doi: 10.1038/s44320-024-00065-2. Online ahead of print. Mol Syst Biol. 2024. PMID: 39322849 - Concomitant presence of a novel ARPP21 variant and CNVs in Chinese familial amyotrophic lateral sclerosis-frontotemporal dementia patients.
Wang Y, Ju R, Jiang J, Mao L, Li X, Deng M. Wang Y, et al. Neurol Sci. 2024 Sep 14. doi: 10.1007/s10072-024-07759-3. Online ahead of print. Neurol Sci. 2024. PMID: 39271636 - High-depth whole-genome sequencing identifies structure variants, copy number variants and short tandem repeats associated with Parkinson's disease.
Wang C, Liu H, Li XY, Ma J, Gu Z, Feng X, Xie S, Tang BS, Chen S, Wang W, Wang J, Zhang J, Chan P. Wang C, et al. NPJ Parkinsons Dis. 2024 Jul 23;10(1):134. doi: 10.1038/s41531-024-00722-1. NPJ Parkinsons Dis. 2024. PMID: 39043730 Free PMC article. - Modification of Huntington's disease by short tandem repeats.
Hong EP, Ramos EM, Aziz NA, Massey TH, McAllister B, Lobanov S, Jones L, Holmans P, Kwak S, Orth M, Ciosi M, Lomeikaite V, Monckton DG, Long JD, Lucente D, Wheeler VC, Gillis T, MacDonald ME, Sequeiros J, Gusella JF, Lee JM. Hong EP, et al. Brain Commun. 2024 Jan 23;6(2):fcae016. doi: 10.1093/braincomms/fcae016. eCollection 2024. Brain Commun. 2024. PMID: 38449714 Free PMC article. - Large-scale genomic rearrangements boost SCRaMbLE in Saccharomyces cerevisiae.
Cheng L, Zhao S, Li T, Hou S, Luo Z, Xu J, Yu W, Jiang S, Monti M, Schindler D, Zhang W, Hou C, Ma Y, Cai Y, Boeke JD, Dai J. Cheng L, et al. Nat Commun. 2024 Jan 26;15(1):770. doi: 10.1038/s41467-023-44511-5. Nat Commun. 2024. PMID: 38278805 Free PMC article.
References
- Feuk L, et al. Structural variation in the human genome. Nat Rev Genet. 2006;7(2):85–97. - PubMed
- Freeman JL, et al. Copy Number Variation: New Insights in Genome Diversity. Genome Research. 2006;16:949–961. - PubMed
- Bridges CB. The Bar ‘gene’: a duplication. Science. 1936;83:210–211. - PubMed
- Jacobs PA, et al. The somatic chromosomes in mongolism. Lancet. 1959;1(7075):710. - PubMed
- Higgs DR, et al. A review of the molecular genetics of the human alpha-globin gene cluster. Blood. 1989;73(5):1081–1104. - PubMed
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous