Implications of Copy Number Variation in People with Chromosomal Abnormalities: Potential for Greater Variation in Copy Number State May Contribute to Variability of Phenotype

Overview

Journal Hugo J

Publisher Springer

Specialty Genetics

Date 2011 Dec 2

PMID 22132061

Citations 8

Authors

Adam J de Smith

Anne L Trewick

Alexandra I F Blakemore

Affiliations

Soon will be listed here.

Abstract

Copy number variation is common in the human genome with many regions, overlapping thousands of genes, now known to be deleted or amplified. Aneuploidies and other forms of chromosomal imbalance have a wide range of adverse phenotypes and are a common cause of birth defects resulting in significant morbidity and mortality. "Normal" copy number variants (CNVs) embedded within the regions of chromosome imbalance may affect the clinical outcomes by altering the local copy number of important genes or regulatory regions: this could alleviate or exacerbate certain phenotypes. In this way CNVs may contribute to the clinical variability seen in many disorders caused by chromosomal abnormalities, such as the congenital heart defects (CHD) seen in ~40% of Down's syndrome (DS) patients. Investigation of CNVs may therefore help to pinpoint critical genes or regulatory elements, elucidating the molecular mechanisms underlying these conditions, also shedding light on the aetiology of such phenotypes in people without major chromosome imbalances, and ultimately leading to their improved detection and treatment.

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References

Li T, Ma X, Sham P, Sun X, Hu X, Wang Q . Evidence for association between novel polymorphisms in the PRODH gene and schizophrenia in a Chinese population. Am J Med Genet B Neuropsychiatr Genet. 2004; 129B(1):13-5. DOI: 10.1002/ajmg.b.30049. View

Czarnecki P, Van Dyke D, Vats S, Feldman G . A mother with VCFS and unilateral dysplastic kidney and her fetus with multicystic dysplastic kidneys: additional evidence to support the association of renal malformations and VCFS. J Med Genet. 1998; 35(4):348. PMC: 1051299. DOI: 10.1136/jmg.35.4.348. View

Nielsen J, Wohlert M . Sex chromosome abnormalities found among 34,910 newborn children: results from a 13-year incidence study in Arhus, Denmark. Birth Defects Orig Artic Ser. 1990; 26(4):209-23. View

Ross J, Roeltgen D, Kushner H, Wei F, Zinn A . The Turner syndrome-associated neurocognitive phenotype maps to distal Xp. Am J Hum Genet. 2000; 67(3):672-81. PMC: 1287527. DOI: 10.1086/303039. View

de Smith A, Tsalenko A, Sampas N, Scheffer A, Yamada N, Tsang P . Array CGH analysis of copy number variation identifies 1284 new genes variant in healthy white males: implications for association studies of complex diseases. Hum Mol Genet. 2007; 16(23):2783-94. DOI: 10.1093/hmg/ddm208. View

Henrichsen C, Vinckenbosch N, Zollner S, Chaignat E, Pradervand S, Schutz F . Segmental copy number variation shapes tissue transcriptomes. Nat Genet. 2009; 41(4):424-9. DOI: 10.1038/ng.345. View

McCarroll S, Huett A, Kuballa P, Chilewski S, Landry A, Goyette P . Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease. Nat Genet. 2009; 40(9):1107-12. PMC: 2731799. DOI: 10.1038/ng.215. View

Greenway S, Pereira A, Lin J, DePalma S, Israel S, Mesquita S . De novo copy number variants identify new genes and loci in isolated sporadic tetralogy of Fallot. Nat Genet. 2009; 41(8):931-5. PMC: 2747103. DOI: 10.1038/ng.415. View

Li C, Guo M, Salas M, Schupf N, Silverman W, Zigman W . Cell type-specific over-expression of chromosome 21 genes in fibroblasts and fetal hearts with trisomy 21. BMC Med Genet. 2006; 7:24. PMC: 1435874. DOI: 10.1186/1471-2350-7-24. View

10.

Shaikh T, Gai X, Perin J, Glessner J, Xie H, Murphy K . High-resolution mapping and analysis of copy number variations in the human genome: a data resource for clinical and research applications. Genome Res. 2009; 19(9):1682-90. PMC: 2752118. DOI: 10.1101/gr.083501.108. View

11.

Le Marechal C, Masson E, Chen J, Morel F, Ruszniewski P, Levy P . Hereditary pancreatitis caused by triplication of the trypsinogen locus. Nat Genet. 2006; 38(12):1372-4. DOI: 10.1038/ng1904. View

12.

Fellermann K, Stange D, Schaeffeler E, Schmalzl H, Wehkamp J, Bevins C . A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn disease of the colon. Am J Hum Genet. 2006; 79(3):439-48. PMC: 1559531. DOI: 10.1086/505915. View

13.

Hasle H . Pattern of malignant disorders in individuals with Down's syndrome. Lancet Oncol. 2002; 2(7):429-36. DOI: 10.1016/S1470-2045(00)00435-6. View

14.

Yang Y, Chung E, Wu Y, Savelli S, Nagaraja H, Zhou B . Gene copy-number variation and associated polymorphisms of complement component C4 in human systemic lupus erythematosus (SLE): low copy number is a risk factor for and high copy number is a protective factor against SLE susceptibility in European.... Am J Hum Genet. 2007; 80(6):1037-54. PMC: 1867093. DOI: 10.1086/518257. View

15.

Park S, MATHEWS R, ZUBERBUHLER J, Rowe R, Neches W, LENOX C . Down syndrome with congenital heart malformation. Am J Dis Child. 1977; 131(1):29-33. DOI: 10.1001/archpedi.1977.02120140031003. View

16.

McKernan K, Peckham H, Costa G, McLaughlin S, Fu Y, Tsung E . Sequence and structural variation in a human genome uncovered by short-read, massively parallel ligation sequencing using two-base encoding. Genome Res. 2009; 19(9):1527-41. PMC: 2752135. DOI: 10.1101/gr.091868.109. View

17.

Habets G, van der Kammen R, Stam J, Michiels F, Collard J . Sequence of the human invasion-inducing TIAM1 gene, its conservation in evolution and its expression in tumor cell lines of different tissue origin. Oncogene. 1995; 10(7):1371-6. View

18.

Singleton A, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J . alpha-Synuclein locus triplication causes Parkinson's disease. Science. 2003; 302(5646):841. DOI: 10.1126/science.1090278. View

19.

Glessner J, Wang K, Cai G, Korvatska O, Kim C, Wood S . Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature. 2009; 459(7246):569-73. PMC: 2925224. DOI: 10.1038/nature07953. View

20.

Conrad D, Pinto D, Redon R, Feuk L, Gokcumen O, Zhang Y . Origins and functional impact of copy number variation in the human genome. Nature. 2009; 464(7289):704-12. PMC: 3330748. DOI: 10.1038/nature08516. View