Major Influence of Repetitive Elements on Disease-associated Copy Number Variants (CNVs)

Overview

Journal Hum Genomics

Publisher Biomed Central

Specialty Genetics

Date 2016 Sep 25

PMID 27663310

Citations 11

Authors

Ana R Cardoso

Manuela Oliveira

Antonio Amorim

Luisa Azevedo

Affiliations

Soon will be listed here.

Abstract

Copy number variants (CNVs) are important contributors to the human pathogenic genetic diversity as demonstrated by a number of cases reported in the literature. The high homology between repetitive elements may guide genomic stability which will give rise to CNVs either by non-allelic homologous recombination (NAHR) or non-homologous end joining (NHEJ). Here, we present a short guide based on previously documented cases of disease-associated CNVs in order to provide a general view on the impact of repeated elements on the stability of the genomic sequence and consequently in the origin of the human pathogenic variome.

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References

Uddin R, Zhang Y, Siu V, Fan Y, OReilly R, Rao J . Breakpoint Associated with a novel 2.3 Mb deletion in the VCFS region of 22q11 and the role of Alu (SINE) in recurring microdeletions. BMC Med Genet. 2006; 7:18. PMC: 1413517. DOI: 10.1186/1471-2350-7-18. View

Shishido E, Aleksic B, Ozaki N . Copy-number variation in the pathogenesis of autism spectrum disorder. Psychiatry Clin Neurosci. 2013; 68(2):85-95. DOI: 10.1111/pcn.12128. View

Zhang F, Seeman P, Liu P, Weterman M, Gonzaga-Jauregui C, Towne C . Mechanisms for nonrecurrent genomic rearrangements associated with CMT1A or HNPP: rare CNVs as a cause for missing heritability. Am J Hum Genet. 2010; 86(6):892-903. PMC: 3032071. DOI: 10.1016/j.ajhg.2010.05.001. View

Azevedo L, Stolnaja L, Tietzeova E, Hrebicek M, Hruba E, Vilarinho L . New polymorphic sites within ornithine transcarbamylase gene: population genetics studies and implications for diagnosis. Mol Genet Metab. 2003; 78(2):152-7. DOI: 10.1016/s1096-7192(03)00019-2. View

Gu W, Zhang F, Lupski J . Mechanisms for human genomic rearrangements. Pathogenetics. 2008; 1(1):4. PMC: 2583991. DOI: 10.1186/1755-8417-1-4. View

Shchelochkov O, Li F, Geraghty M, Gallagher R, Van Hove J, Lichter-Konecki U . High-frequency detection of deletions and variable rearrangements at the ornithine transcarbamylase (OTC) locus by oligonucleotide array CGH. Mol Genet Metab. 2009; 96(3):97-105. DOI: 10.1016/j.ymgme.2008.11.167. View

Borun P, De Rosa M, Nedoszytko B, Walkowiak J, Plawski A . Specific Alu elements involved in a significant percentage of copy number variations of the STK11 gene in patients with Peutz-Jeghers syndrome. Fam Cancer. 2015; 14(3):455-61. PMC: 4559094. DOI: 10.1007/s10689-015-9800-5. View

Van Esch H . MECP2 Duplication Syndrome. Mol Syndromol. 2012; 2(3-5):128-136. PMC: 3366699. DOI: 10.1159/000329580. View

Willatt L, Cox J, Barber J, Dachs Cabanas E, Collins A, Donnai D . 3q29 microdeletion syndrome: clinical and molecular characterization of a new syndrome. Am J Hum Genet. 2005; 77(1):154-60. PMC: 1226188. DOI: 10.1086/431653. View

10.

Inoue K, Osaka H, Thurston V, Clarke J, Yoneyama A, Rosenbarker L . Genomic rearrangements resulting in PLP1 deletion occur by nonhomologous end joining and cause different dysmyelinating phenotypes in males and females. Am J Hum Genet. 2002; 71(4):838-53. PMC: 378540. DOI: 10.1086/342728. View

11.

Giorgio E, Rolyan H, Kropp L, Chakka A, Yatsenko S, Di Gregorio E . Analysis of LMNB1 duplications in autosomal dominant leukodystrophy provides insights into duplication mechanisms and allele-specific expression. Hum Mutat. 2013; 34(8):1160-71. PMC: 3714349. DOI: 10.1002/humu.22348. View

12.

Antonell A, de Luis O, Domingo-Roura X, Perez-Jurado L . Evolutionary mechanisms shaping the genomic structure of the Williams-Beuren syndrome chromosomal region at human 7q11.23. Genome Res. 2005; 15(9):1179-88. PMC: 1199532. DOI: 10.1101/gr.3944605. View

13.

Dittwald P, Gambin T, Szafranski P, Li J, Amato S, Divon M . NAHR-mediated copy-number variants in a clinical population: mechanistic insights into both genomic disorders and Mendelizing traits. Genome Res. 2013; 23(9):1395-409. PMC: 3759717. DOI: 10.1101/gr.152454.112. View

14.

Toft M, Ross O . Copy number variation in Parkinson's disease. Genome Med. 2010; 2(9):62. PMC: 3092113. DOI: 10.1186/gm183. View

15.

Ji Y, Gottlieb W, Depinet T, Wandstrat A, Cassidy S, Driscoll D . Chromosome breakage in the Prader-Willi and Angelman syndromes involves recombination between large, transcribed repeats at proximal and distal breakpoints. Am J Hum Genet. 1999; 65(2):370-86. PMC: 1377936. DOI: 10.1086/302510. View

16.

Firth H, Richards S, Bevan A, Clayton S, Corpas M, Rajan D . DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources. Am J Hum Genet. 2009; 84(4):524-33. PMC: 2667985. DOI: 10.1016/j.ajhg.2009.03.010. View

17.

Ferreira F, Esteves S, Almeida L, Gaspar A, da Costa C, Janeiro P . Trimethylaminuria (fish odor syndrome): genotype characterization among Portuguese patients. Gene. 2013; 527(1):366-70. DOI: 10.1016/j.gene.2013.05.025. View

18.

Bergmann C, Zerres K, Senderek J, Rudnik-Schoneborn S, Eggermann T, Hausler M . Oligophrenin 1 (OPHN1) gene mutation causes syndromic X-linked mental retardation with epilepsy, rostral ventricular enlargement and cerebellar hypoplasia. Brain. 2003; 126(Pt 7):1537-44. DOI: 10.1093/brain/awg173. View

19.

SMIT A . The origin of interspersed repeats in the human genome. Curr Opin Genet Dev. 1996; 6(6):743-8. DOI: 10.1016/s0959-437x(96)80030-x. View

20.

Ballif B, Theisen A, Coppinger J, Gowans G, Hersh J, Madan-Khetarpal S . Expanding the clinical phenotype of the 3q29 microdeletion syndrome and characterization of the reciprocal microduplication. Mol Cytogenet. 2008; 1:8. PMC: 2408925. DOI: 10.1186/1755-8166-1-8. View