Advertisement

Chromosomal Microarray in the New High-Throughput Technological and Bioinformatic Era

  • Susan MathewEmail author
Chapter
  • 732 Downloads

Abstract

Conventional karyotyping is the gold standard for identifying chromosomal abnormalities in human diseases. The advances in DNA technology and molecular genetics resulted in the introduction of fluorescence in situ hybridization and other technologies in cytogenetics. Chromosomal microarrays have taken the field of cytogenetics to the next level by identifying microdeletions, microduplications, copy number variants and loss of heterozygosity. This chapter explores its applications and its profound impact on the diagnosis and prognosis of individuals with unexplained developmental delay/intellectual delay, autism spectral disorders and multiple congenital abnormalities. This chapter also highlights its applications in prenatal diagnosis and cancer.

Keywords

Chromosomal microarray Microdeletion Microduplication Prenatal diagnosis Cancer diagnostics Congenital malformations Copy number variants 

Abbreviations

aCGH

Array comparative genomic hybridization

ASD

Autism spectrum disorders

CMA

Chromosomal microarray analysis

CNV

Copy number variants

DD

Developmental delay

FISH

Fluorescence in situ hybridization

ID

Intellectual disability

LCSH

Long contiguous stretches of homozygosity

LOH

Loss of heterozygosity

MCA

Multiple congenital anomalies

NGS

Next-generation sequencing

VISL

Variants in susceptibility loci

VOUS

Variants of uncertain significance

References

  1. ACOG Committee (2009) Opinion No. 446: array comparative genomic hybridization in prenatal diagnosis. Obstet Gynecol 114(5):1161–1163.  https://doi.org/10.1097/AOG.0b013e3181c33cadCrossRefGoogle Scholar
  2. Agnelli L, Mosca L, Fabris S, Lionetti M, Andronache A, Kwee I, Todoerti K, Verdelli D, Battaglia C, Bertoni F, Deliliers GL, Neri A (2009) A SNP microarray and FISH-based procedure to detect allelic imbalances in multiple myeloma: an integrated genomics approach reveals a wide gene dosage effect. Genes Chromosomes Cancer 48(7):603–614.  https://doi.org/10.1002/gcc.20668CrossRefPubMedGoogle Scholar
  3. Alexiev BA, Zou YS (2014) Clear cell papillary renal cell carcinoma: a chromosomal microarray analysis for two cases using a novel Molecular Inversion Probe (MIP) technology. Pathol Res Pract 210:1049–1053PubMedCrossRefGoogle Scholar
  4. Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson J Jr, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grever MR, Byrd JC, Botstein D, Brown PO, Staudt LM (2000) Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403:503–511PubMedPubMedCentralCrossRefGoogle Scholar
  5. American College of Obstetricians and Gynecologists Committee on Genetics (2013) Committee Opinion No. 581: the use of chromosomal microarray analysis in prenatal diagnosis. Obstet Gynecol 122(6):1374–1377.  https://doi.org/10.1097/01.AOG.0000438962.16108.d1CrossRefGoogle Scholar
  6. Arenillas L, Mallo M, Ramos F, Guinta K, Barragán E, Lumbreras E, Larráyoz MJ, De Paz R, Tormo M, Abáigar M, Pedro C, Cervera J, Such E, José Calasanz M, Díez-Campelo M, Sanz GF, Hernández JM, Luño E, Saumell S, Maciejewski J, Florensa L, Solé F (2013) Single nucleotide polymorphism array karyotyping: a diagnostic and prognostic tool in myelodysplastic syndromes with unsuccessful conventional cytogenetic testing. Genes Chromosomes Cancer 52(12):1167–1177.  https://doi.org/10.1002/gcc.22112CrossRefPubMedGoogle Scholar
  7. Armengol G, Canellas A, Alvarez Y, Bastida P, Toledo JS, Pérez-Iribarne Mdel M, Camós M, Tuset E, Estella J, Coll MD, Caballín MR, Knuutila S (2010) Genetic changes including gene copy number lterations and their relation to prognosis in childhood acute myeloid leukemia. Leuk Lymphoma 51:114–124PubMedCrossRefGoogle Scholar
  8. Armengol L, Nevado J, Serra-Juhé C, Plaja A, Mediano C, García-Santiago FA, García-Aragonés M, Villa O, Mansilla E, Preciado C, Fernández L, Ángeles Mori M, García-Pérez L, Lapunzina PD, Pérez-Jurado LA (2012) Clinical utility of chromosomal microarray analysis in invasive prenatal diagnosis. Hum Genet 131:513–523.  https://doi.org/10.1007/s00439-011-1095-5CrossRefPubMedGoogle Scholar
  9. Astbury C, Christ LA, Aughton DJ, Cassidy SB, Kumar A, Eichler EE, Schwartz S (2004) Detection of deletions in de novo “balanced” chromosome rearrangements: further evidence for their role in phenotypic abnormalities. Genet Med 6:81–89PubMedCrossRefPubMedCentralGoogle Scholar
  10. Autism and Developmental Monitoring Network Surveillance Year (2000) Principal Investigators (2007) Prevalence of autism spectrum disorders–autism and developmental disabilities monitoring network, six sites, United States. MMWR Surveill Summ 56:1–11Google Scholar
  11. Bachmann-Gagescu R, Mefford HC, Cowan C, Glew GM, Hing AV, Wallace S, Bader PI, Hamati A, Reitnauer PJ, Smith R, Stockton DW, Muhle H, Helbig I, Eichler EE, Ballif BC, Rosenfeld J, Tsuchiya KD (2010) Recurrent 200-kb deletions of 16p11.2 that include the SH2B1 gene are associated with developmental delay and obesity. Genet Med 12(10):641–647.  https://doi.org/10.1097/GIM.0b013e3181ef4286CrossRefPubMedPubMedCentralGoogle Scholar
  12. Baker P, Piven J, Schwartz S, Patil S (1994) Brief report: duplication of chromosome 15q11-13 in two individuals with autistic disorder. J Autism Dev Disord 24:529PubMedCrossRefPubMedCentralGoogle Scholar
  13. Ballif BC, Theisen A, McDonald-McGinn DM, Zackai EH, Hersh JH, Bejjani BA, Shaffer LG (2008) (2Identification of a previously unrecognized microdeletion syndrome of 16q11.2q12.2.008). Clin Genet. 74(5):469–75.  https://doi.org/10.1111/j.1399-0004.2008.01094.x.PMID:18811697
  14. Baughn LB, Biegel JA, South ST, Smolarek TA, Volkert S, Carroll AJ, Heerema NA, Rabin KR, Zweidler-McKay PA, Loh M, Hirsch B (2015). Integration of cytogenomic data for furthering the characterization of pediatric B-cell acute lymphoblastic leukemia: a multi-institution, multi-platform microarray study. Cancer Genet. 208(1-2):1–18.  https://doi.org/10.1016/j.cancergen.2014.11.003.PubMedCrossRefPubMedCentralGoogle Scholar
  15. Berg JS, Brunetti-Pierri N, Peters SU, Kang SH, Fong CT, Salamone J, Freedenberg D, Hannig VL, Prock LA, Miller DT, Raffalli P, Harris DJ, Erickson RP, Cunniff C, Clark GD, Blazo MA, Peiffer DA, Gunderson KL, Sahoo T, Patel A, Lupski JR, Beaudet AL, Cheung SW (2007) Speech delay and autism spectrum behaviors are frequently associated with duplication of the 7q11.23 Williams-Beuren syndrome region. Genet Med 9(7):427–441. doi: 10.1097GIM.0b013e3180986192Google Scholar
  16. Blow N (2007) Tissue preparation: Tissue issues. Nature 448(7156):959–963PubMedCrossRefPubMedCentralGoogle Scholar
  17. Bolton PF, Dennis NR, Browne CE, Thomas NS, Veltman MW, Thompson RJ, Jacobs P (2001) The phenotypic manifestations of interstitial duplications of proximal 15q with special reference to the autistic spectrum disorders. Am J Med Genet 105(8):675–685PubMedCrossRefPubMedCentralGoogle Scholar
  18. Bornstein E, Berger S, Cheung SW, Maliszewski KT, Patel A, Pursley AN, Lenchner E, Bacino C, Beaudet AL, Divon MY (2017) Universal prenatal chromosomal microarray analysis: additive value and clinical dilemmas in fetuses with a normal karyotype. Am J Perinatol 34(4):340–348.  https://doi.org/10.1055/s-0036-1586501CrossRefPubMedPubMedCentralGoogle Scholar
  19. Brabbing-Goldstein D, Reches A, Svirsky R, Bar-Shira A, Yaron Y (2018) Dilemmas in genetic counseling for low-penetrance neuro-susceptibility loci detected on prenatal chromosomal microarray analysis. Am J Obstet Gynecol 218(2):247.e1–247.e12.  https://doi.org/10.1016/j.ajog.2017.11.559CrossRefGoogle Scholar
  20. Breman A, Pursley AN, Hixson P, Bi W, Ward P, Bacino CA, Shaw C, Lupski JR, Beaudet A, Patel A, Cheung SW, Van den Veyver I (2012) Prenatal chromosomal microarray analysis in a diagnostic laboratory; experience with >1000 cases and review of the literature. Prenat Diagn 32(4):351–361.  https://doi.org/10.1002/pd.3861CrossRefPubMedPubMedCentralGoogle Scholar
  21. Brunetti-Pierri N, Berg JS, Scaglia F, Belmont J, Bacino CA, Sahoo T, Lalani SR, Graham B, Lee B, Shinawi M, Shen J, Kang SH, Pursley A, Lotze T, Kennedy G, Lansky-Shafer S, Weaver C, Roeder ER, Grebe TA, Arnold GL, Hutchison T, Reimschisel T, Amato S, Geragthy MT, Innis JW, Obersztyn E, Nowakowska B, Rosengren SS, Bader PI, Grange DK, Naqvi S, Garnica AD, Bernes SM, Fong CT, Summers A, Walters WD, Lupski JR, Stankiewicz P, Cheung SW, Patel A (2008) Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities. Nat Genet 40(12):1466–1471.  https://doi.org/10.1038/ng.279CrossRefPubMedPubMedCentralGoogle Scholar
  22. Brynn L, Wapner R (2018) Prenatal diagnosis by chromosomal microarray analysis. Fertil Steril 109(2):201–212CrossRefGoogle Scholar
  23. Bullinger L, Döhner K, Bair E, Fröhling S, Schlenk RF, Tibshirani R, Döhner H, Pollack JR (2004) Use of gene-expression profiling to identify prognostic subclasses in adult acute myeloid leukemia. N Engl J Med 350(16):1605–1616PubMedCrossRefPubMedCentralGoogle Scholar
  24. Callaway JL, Shaffer LG, Chitty LS, Rosenfeld JA, Crolla JA (2013) The clinical utility of microarray technologies applied to prenatal cytogenetics in the presence of a normal conventional karyotype: a review of the literature. Prenat Diagn 233(12):1119–1123.  https://doi.org/10.1002/pd.4209CrossRefGoogle Scholar
  25. Carter NP (2007) Methods and strategies for analyzing copy number variation using DNA microarrays. Nat Genet 39:S16–S21PubMedPubMedCentralCrossRefGoogle Scholar
  26. Cavalli P, Cavallari U, Novelli A (2012) Array CGH in routine prenatal diagnosis practice. Prenat Diagn 32:708–709, author reply 11–2PubMedCrossRefPubMedCentralGoogle Scholar
  27. Chan YM, Leung WC, Chan WP, Leung TY, Cheng YK, Sahota DS (2015) Women’s uptake of non-invasive DNA testing following a high-risk screening test for trisomy 21 within a publicly funded healthcare system: findings from a retrospective review. Prenat Diagn 35(4):342–347.  https://doi.org/10.1002/pd.4544CrossRefPubMedPubMedCentralGoogle Scholar
  28. Chetty S, Garabedian MJ, Norton ME (2013) Uptake of noninvasive prenatal testing (NIPT) in women following positive aneuploidy screening. Prenat Diagn 33:542–546PubMedCrossRefPubMedCentralGoogle Scholar
  29. Cooley LD, Lebo M, Li MM, Slovak ML, Wolff DJ, Working Group of the American College of Medical Genetics and Genomics (ACMG) Laboratory Quality Assurance Committee (2013) American College of Medical Genetics and Genomics technical standards and guidelines: microarray analysis for chromosome abnormalities in neoplastic disorders. Genet Med 15(6):484–494.  https://doi.org/10.1038/gim.2013.49CrossRefPubMedPubMedCentralGoogle Scholar
  30. Cooper GM, Coe BP, Girirajan S, Rosenfeld JA, Vu TH, Baker C, Williams C, Stalker H, Hamid R, Hannig V, Abdel-Hamid H, Bader P, McCracken E, Niyazov D, Leppig K, Thiese H, Hummel M, Alexander N, Gorski J, Kussmann J, Shashi V, Johnson K, Rehder C, Ballif BC, Shaffer LG, Eichler EE (2011) A copy number variation morbidity map of developmental delay. Nat Genet 43(9):838–846.  https://doi.org/10.1038/ng.909CrossRefPubMedPubMedCentralGoogle Scholar
  31. Coughlin CR II, Scharer GH, Shaikh TH (2012) Clinical impact of copy number variation analysis using high-resolution microarray technologies: advantages, limitations and concerns. Genome Med 4:80PubMedPubMedCentralCrossRefGoogle Scholar
  32. Cukier HN, Lee JM, Ma D, Young JI, Mayo V, Butler BL, Ramsook SS, Rantus JA, Abrams AJ, Whitehead PL, Wright HH, Abramson RK, Haines JL, Cuccaro ML, Pericak-Vance MA, Gilbert JR (2012) The expanding role of MBD genes in autism: identification of a MECP2 duplication and novel alterations in MBD5, MBD6, and SETDB1. Autism Res 5(6):385–397.  https://doi.org/10.1002/aur.1251CrossRefPubMedPubMedCentralGoogle Scholar
  33. de Vries BB, Pfundt R, Leisink M, Koolen DA, Vissers LE, Janssen IM, Sv R, Nillesen WM, Huys EH, Nd L, Smeets D, Sistermans EA, Feuth T, van Ravenswaaij-Arts CM, van Kessel AG, Schoenmakers EF, Brunner HG, Veltman JA (2005) Diagnostic genome profiling in mental retardation. Am J Hum Genet 77(4):606–616PubMedPubMedCentralCrossRefGoogle Scholar
  34. Donnelly JC, Platt LD, Rebarber A, Zachary J, Grobman WA, Wapner RJ (2014) Association of copy number variants with specific ultrasonographically detected fetal anomalies. Obstet Gynecol 124(1):83–90.  https://doi.org/10.1097/AOG.0000000000000336CrossRefPubMedPubMedCentralGoogle Scholar
  35. Duncan A, Langlois S, SOGC Genetics Committee, CCMG Prenatal Diagnosis Committee (2011) Use of array genomic hybridization technology in prenatal diagnosis in Canada. J Obstet Gynaecol Can 33(12):1256–1259PubMedCrossRefPubMedCentralGoogle Scholar
  36. Dugoff L, Norton ME, Kuller JA. (2016) The use of chromosomal microarray for prenatal diagnosis. Society of Maternal Fetal medicine (SMFM) Consult Series #41 L Published by Elsevier Inc. http://dx.doi.org/10.1016/j.ajog.2016.07.016
  37. Ebert BL, Golub TR (2004) Genomic approaches to hematologic malignancies. Blood 104:923–932PubMedCrossRefPubMedCentralGoogle Scholar
  38. Faas BH, van der Burgt I, Kooper AJ, Pfundt R, Hehir-Kwa JY, Smits AP, de Leeuw N (2010) Identification of clinically significant, submicroscopic chromosome alterations and UPD in fetuses with ultrasound anomalies using genome-wide 250k SNP array analysis. J Med Genet 47(9):586–594.  https://doi.org/10.1136/jmg.2009.075853CrossRefPubMedPubMedCentralGoogle Scholar
  39. Franco LM, de Ravel T, Graham BH, Frenkel SM, Van Driessche J, Stankiewicz P, Lupski JR, Vermeesch JR, Cheung SW (2010) A syndrome of short stature, microcephaly and speech delay is associated with duplications reciprocal to the common Sotos syndrome deletion. Eur J Hum Genet 18(2):258–261.  https://doi.org/10.1038/ejhg.2009.164CrossRefPubMedPubMedCentralGoogle Scholar
  40. Fruhman G, Van den Veyver IB (2010) Applications of array comparative genomic hybridization in obstetrics. Obstet Gynecol Clin N Am 37:71–85CrossRefGoogle Scholar
  41. Golub TR, Slonim DK, Tamayo P, Huard C, Gaasenbeek M, Mesirov JP, Coller H, Loh ML, Downing JR, Caligiuri MA, Bloomfield CD, Lander ES (1999) Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 286(5439):531–537CrossRefGoogle Scholar
  42. Goobie S, Knijnenburg J, Fitzpatrick D, Sharkey FH, Lionel AC, Marshall CR, Azam T, Shago M, Chong K, Mendoza-Londono R, den Hollander NS, Ruivenkamp C, Maher E, Tanke HJ, Szuhai K, Wintle RF, Scherer SW (2008) Molecular and clinical characterization of de novo and familial cases with microduplicatio 3q29: guidelines for copy number variation case reporting. Cytogeneti Genome Res 123:65–68.  https://doi.org/10.1159/000184693CrossRefGoogle Scholar
  43. Gorringe KL, Hunter SM, Pang JM, Opeskin K, Hill P, Rowley SM, Choong DY, Thompson ER, Dobrovic A, Fox SB, Mann GB, Campbell IG (2015) Copy number analysis of ductal carcinoma in situ with and without recurrence. Mod Pathol 28(9):1174–1184.  https://doi.org/10.1038/modpathol.2015.75CrossRefGoogle Scholar
  44. Gresham D, Dunham MJ, Botstein D (2008) Comparing whole genomes using DNA microarrays. Nat Rev Genet 9:291–302PubMedCrossRefPubMedCentralGoogle Scholar
  45. Gunnarsson R, Staaf J, Jansson M, Ottesen AM, Göransson H, Liljedahl U, Ralfkiaer U, Mansouri M, Buhl AM, Smedby KE, Hjalgrim H, Syvänen AC, Borg A, Isaksson A, Jurlander J, Juliusson G, Rosenquist R (2008) Screening for copy-number alterations and loss of heterozygosity in chronic lymphocytic leukemia -a comparative study of four differently designed, high resolution microarray platforms. Genes Chromosomes Cancer 47(8):697–711.  https://doi.org/10.1002/gcc.20575CrossRefPubMedPubMedCentralGoogle Scholar
  46. Hawthorn L, Cowell JK (2011) Analysis of Wilms Tumors using SNP mapping array based comparative genomic hybridization. PLoS One 6(4):e18941PubMedPubMedCentralCrossRefGoogle Scholar
  47. Helbig I, Mefford HC, Sharp AJ, Guipponi M, Fichera M, Franke A, Muhle H, de Kovel C, Baker C, von Spiczak S, Kron KL, Steinich I, Kleefuss-Lie AA, Leu C, Gaus V, Schmitz B, Klein KM, Reif PS, Rosenow F, Weber Y, Lerche H, Zimprich F, Urak L, Fuchs K, Feucht M, Genton P, Thomas P, Visscher F, de Haan GJ, Møller RS, Hjalgrim H, Luciano D, Wittig M, Nothnagel M, Elger CE, Nürnberg P, Romano C, Malafosse A, Koeleman BP, Lindhout D, Stephani U, Schreiber S, Eichler EE, Sander T (2009) 15q13.3 microdeletions increase risk of idiopathic generalized epilepsy. Nat Genet 41(2):160–162.  https://doi.org/10.1038/ng.292CrossRefPubMedPubMedCentralGoogle Scholar
  48. Higgins AW, Alkuraya FS, Bosco AF, Brown KK, Bruns GA, Donovan DJ, Eisenman R, Fan Y, Farra CG, Ferguson HL, Gusella JF, Harris DJ, Herrick SR, Kelly C, Kim HG, Kishikawa S, Korf BR, Kulkarni S, Lally E, Leach NT, Lemyre E, Lewis J, Ligon AH, Lu W, Maas RL, MacDonald ME, Moore SD, Peters RE, Quade BJ, Quintero-Rivera F, Saadi I, Shen Y, Shendure J, Williamson RE, Morton CC (2008) Characterization of apparently balanced chromosomal rearrangements from the developmental genome anatomy project. Am J Hum Genet 82:712–722.  https://doi.org/10.1016/j.ajhg.2008.01.011CrossRefPubMedPubMedCentralGoogle Scholar
  49. Hillman SC, McMullan DJ, Hall G, Togneri FS, James N, Maher EJ, Meller CH, Williams D, Wapner RJ, Maher ER, Kilby MD (2013) Use of prenatal chromosomal microarray: prospective cohort study and systematic review and meta-analysis. Ultrasound Obstet Gynecol 41(6):610–620.  https://doi.org/10.1002/uog.12464CrossRefPubMedPubMedCentralGoogle Scholar
  50. Hochstenbach R, van Amstel PHK, Poot M (2006) Microarray-based genome investigation: molecular karyotyping or segmental aneuploidy profiling? Eur J Hum Genet 14:262–265PubMedCrossRefPubMedCentralGoogle Scholar
  51. Hoyer J, Dreweke A, Becker C, Göhring I, Thiel CT, Peippo MM, Rauch R, Hofbeck M, Trautmann U, Zweier C, Zenker M, Hüffmeier U, Kraus C, Ekici AB, Rüschendorf F, Nürnberg P, Reis A, Rauch A (2007) Molecular karyotyping in patients with mental retardation using 100K single-nucleotide polymorphism arrays. J Med Genet 44(10):629–636PubMedPubMedCentralCrossRefGoogle Scholar
  52. Inda MM, Perot C, Guillaud-Bataille M, Danglot G, Rey JA, Bello MJ, Fan X, Eberhart C, Zazpe I, Portillo E, Tuñón T, Martínez-Peñuela JM, Bernheim A, Castresana JS (2005) Genetic heterogeneity in supratentorial and infratentorial primitive neuroectodermal tumours of the central nervous system. Histopathology 47(6):631–637PubMedCrossRefPubMedCentralGoogle Scholar
  53. International Schizophrenia Consortium (2008) Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 455(7210):237–241.  https://doi.org/10.1038/nature07239CrossRefGoogle Scholar
  54. Jung HS, Leffers JA, Tsongalis GJ (2017) Utilization of the oncoscan microarray assay in cancer diagnostics. Applied Cancer Research 37:1.  https://doi.org/10.1186/s41241-016-0007-3CrossRefGoogle Scholar
  55. Kagawa N, Maruno M, Suzuki T, Hashiba T, Hashimoto N, Izumoto S, Yoshimine T (2006) Detection of genetic and chromosomal aberrations in medulloblastomas and primitive neuroectodermal tumors with DNA microarrays. Brain Tumor Pathol 23:41–47.  https://doi.org/10.1007/s10014-006-0201-1CrossRefPubMedPubMedCentralGoogle Scholar
  56. Kaminsky EB, Kaul V, Paschall J, Church DM, Bunke B, Kunig D, Moreno-De-Luca D, Moreno-De-Luca A, Mulle JG, Warren ST, Richard G, Compton JG, Fuller AE, Gliem TJ, Huang S, Collinson MN, Beal SJ, Ackley T, Pickering DL, Golden DM, Aston E, Whitby H, Shetty S, Rossi MR, Rudd MK, South ST, Brothman AR, Sanger WG, Iyer RK, Crolla JA, Thorland EC, Aradhya S, Ledbetter DH, Martin CL (2011) An evidence based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities. Genet Med 13(9):777–784.  https://doi.org/10.1097/GIM.0b013e31822c79f9CrossRefPubMedPubMedCentralGoogle Scholar
  57. Kantaputra PN, Klopocki E, Hennig BP, Praphanphoj V, Le Caignec C, Isidor B, Kwee ML, Shears DJ, Mundlos S (2010) Mesomelic dysplasia Kantaputra type is associated with duplications of the HOXD locus on chromosome 2q. Eur J Hum Genet 18(12):1310–1314.  https://doi.org/10.1038/ejhg.2010.116CrossRefPubMedPubMedCentralGoogle Scholar
  58. Kearney HM, Thorland EC, Brown KK, Quintero-Rivera F, South ST, Working Group of the American College of Medical Genetics Laboratory Quality Assurance Committee (2011) American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genet Med 13(7):680–685.  https://doi.org/10.1097/GIM.0b013e3182217a3aCrossRefPubMedPubMedCentralGoogle Scholar
  59. Kolquist KA, Schultz RA, Furrow A, Brown TC, Han JY, Campbell LJ, Wall M, Slovak ML, Shaffer LG, Ballif BC (2011) Microarray-based comparative genomic hybridization of cancer targets reveals novel, recurrent genetic aberrations in the myelodysplatic syndromes. Cancer Genet 204(11):603–628.  https://doi.org/10.1016/j.cancergen.2011.10.004CrossRefPubMedPubMedCentralGoogle Scholar
  60. Koolen DA, Vissers LE, Pfundt R, de Leeuw N, Knight SJ, Regan R, Kooy RF, Reyniers E, Romano C, Fichera M, Schinzel A, Baumer A, Anderlid BM, Schoumans J, Knoers NV, van Kessel AG, Sistermans EA, Veltman JA, Brunner HG, de Vries BB (2006) A new chromosome 17q21.31 microdeletion syndrome associated with a common inversion polymorphism. Nat Genet 38:999–1001.  https://doi.org/10.1038/ng1853CrossRefPubMedPubMedCentralGoogle Scholar
  61. Kuga D, Mizoguchi M, Guan Y, Hata N, Yoshimoto K, Shono T, Suzuki SO, Kukita Y, Tahira T, Nagata S, Sasaki T, Hayashi K (2008) Prevalence of copy-number neutral LOH in glioblastomas revealed by genomewide analysis of laser-microdissected tissues. Neuro-Oncology 10(6):995–1003.  https://doi.org/10.1215/15228517-2008-064CrossRefPubMedPubMedCentralGoogle Scholar
  62. Lander J, Ware SM (2014) Copy number variation in congenital heart defects. Current Genetic Medicine Reports 2(3):168–178CrossRefGoogle Scholar
  63. Laurie CC, Laurie CA, Smoley SA, Carlson EE, Flinn I, Fridley BL, Greisman HA, Gribben JG, Jelinek DF, Nelson SC, Paietta E, Schaid D, Sun Z, Tallman MS, Weinshilboum R, Kay NE, Shanafelt TD (2014) Acquired chromosomal anomalies in chronic lymphocytic leukemia patients compared with more than 50,000 quasi-normal participants. Cancer Genet 207(1–2):19–30.  https://doi.org/10.1016/j.cancergen.2014.01.004CrossRefPubMedPubMedCentralGoogle Scholar
  64. Lewis F, Maughan NJ, Smith V, Hillan K, Quirke P (2001) Unlocking the archive--gene expression in paraffin-embedded tissue. J Pathol 195(1):66–71.  https://doi.org/10.1002/1096-9896(200109)195:1<66::AID-PATH921>3.0.CO;2-FCrossRefPubMedPubMedCentralGoogle Scholar
  65. Lisi EC, Hamosh A, Doheny KF, Squibb E, Jackson B, Galczynski R, Thomas GH, Batista DA (2008) 3q29 interstitial microduplication: a new syndrome in a three-generation family. Am J Med Genet A 146A(5):601–609.  https://doi.org/10.1002/ajmg.a.32190CrossRefPubMedPubMedCentralGoogle Scholar
  66. Manning M, Hudgins L (2010) Professional Practice and Guidelines Committee. Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. Genet Med 12:742–745PubMedPubMedCentralCrossRefGoogle Scholar
  67. Martin CL, Kirkpatrick BE, Ledbetter DH (2015) Copy number variants, aneuploidies, and human disease. Clin Perinatol 42:227–242PubMedPubMedCentralCrossRefGoogle Scholar
  68. McDonald-McGinn DM, Sullivan KE (2011) Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Medicine (Baltimore) 90:1–18CrossRefGoogle Scholar
  69. McGowan-Jordan J, Simons A, and Schmid M, Editors (2016). ISCN: An International System for Human Cytogenomic Nomenclature (2016). ISBN 978–3–318–05857–4Google Scholar
  70. Mefford HC (2009) Genotype to phenotype-discovery and characterization of novel genomic disorders in a “genotype-first” era. Genet Med 11:836–842PubMedCrossRefGoogle Scholar
  71. Mefford HC, Sharp AJ, Baker C, Itsara A, Jiang Z, Buysse K, Huang S, Maloney VK, Crolla JA, Baralle D, Collins A, Mercer C, Norga K, de Ravel T, Devriendt K, Bongers EM, de Leeuw N, Reardon W, Gimelli S, Bena F, Hennekam RC, Male A, Gaunt L, Clayton-Smith J, Simonic I, Park SM, Mehta SG, Nik-Zainal S, Woods CG, Firth HV, Parkin G, Fichera M, Reitano S, Lo Giudice M, Li KE, Casuga I, Broomer A, Conrad B, Schwerzmann M, Räber L, Gallati S, Striano P, Coppola A, Tolmie JL, Tobias ES, Lilley C, Armengol L, Spysschaert Y, Verloo P, De Coene A, Goossens L, Mortier G, Speleman F, van Binsbergen E, Nelen MR, Hochstenbach R, Poot M, Gallagher L, Gill M, McClellan J, King MC, Regan R, Skinner C, Stevenson RE, Antonarakis SE, Chen C, Estivill X, Menten B, Gimelli G, Gribble S, Schwartz S, Sutcliffe JS, Walsh T, Knight SJ, Sebat J, Romano C, Schwartz CE, Veltman JA, de Vries BB, Vermeesch JR, Barber JC, Willatt L, Tassabehji M, Eichler EE (2008) Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes. N Engl J Med 359(16):1685–1699.  https://doi.org/10.1056/NEJMoa0805384CrossRefPubMedPubMedCentralGoogle Scholar
  72. Mefford HC, Yendle SC, Hsu C, Cook J, Geraghty E, McMahon JM, Eeg-Olofsson O, Sadleir LG, Gill D, Ben-Zeev B, Lerman-Sagie T, Mackay M, Freeman JL, Andermann E, Pelakanos JT, Andrews I, Wallace G, Eichler EE, Berkovic SF, Scheffer IE (2011) Rare copy number variants are an important cause of epileptic encephalopathies. Ann Neurol 70(6):974–985.  https://doi.org/10.1002/ana.22645CrossRefPubMedPubMedCentralGoogle Scholar
  73. Mefford HC, Batshaw ML, Hoffman EP (2012) Genomics, intellectual disability, and autism. N Engl J Med 366:733–743PubMedPubMedCentralCrossRefGoogle Scholar
  74. Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, Church DM, Crolla JA, Eichler EE, Epstein CJ, Faucett WA, Feuk L, Friedman JM, Hamosh A, Jackson L, Kaminsky EB, Kok K, Krantz ID, Kuhn RM, Lee C, Ostell JM, Rosenberg C, Scherer SW, Spinner NB, Stavropoulos DJ, Tepperberg JH, Thorland EC, Vermeesch JR, Waggoner DJ, Watson MS, Martin CL, Ledbetter DH (2010) Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 86(5):749–764.  https://doi.org/10.1016/j.ajhg.2010.04.006CrossRefPubMedPubMedCentralGoogle Scholar
  75. Mullegama SV, Alaimo JT, Chen L, Elsea SH (2015) Phenotypic and molecular convergence of 2q23.1 deletion syndrome with other neurodevelopmental syndromes associated with autism spectrum disorder. Int J Mol Sci 16(4):7627–7643.  https://doi.org/10.3390/ijms16047627CrossRefPubMedPubMedCentralGoogle Scholar
  76. Nachman JB, Heerema NA, Sather H, Camitta B, Forestier E, Harrison CJ, Dastugue N, Schrappe M, Pui CH, Basso G, Silverman LB, Janka-Schaub GE (2007) Outcome of treatment in children with hypodiploid acute lymphoblastic leukemia. Blood 110:1112–1115.  https://doi.org/10.1182/blood-2006-07-038299CrossRefPubMedPubMedCentralGoogle Scholar
  77. Newschaffer CJ, Croen LA, Daniels J, Giarelli E, Grether JK, Levy SE, Mandell DS, Miller LA, Pinto-Martin J, Reaven J, Reynolds AM, Rice CE, Schendel D, Windham GC (2007) The epidemiology of autism spectrum disorders. Annu Rev Public Health 28:235–258.  https://doi.org/10.1146/annurev.publhealth.28.021406.144007CrossRefPubMedPubMedCentralGoogle Scholar
  78. Novelli A, Grati FR, Ballarati L, Bernardini L, Bizzoco D, Camurri L, Casalone R, Cardarelli L, Cavalli P, Ciccone R, Clementi M, Dalprà L, Gentile M, Gelli G, Grammatico P, Malacarne M, Nardone AM, Pecile V, Simoni G, Zuffardi O, Giardino D (2012) Microarray application in prenatal diagnosis: a position statement from the cytogenetics working group of the Italian Society of Human Genetics (SIGU), November 2011. Ultrasound Obstet Gynecol 39(4):384–388.  https://doi.org/10.1002/uog.11092CrossRefPubMedPubMedCentralGoogle Scholar
  79. Okamoto R, Ogawa S, Nowak D, Kawamata N, Akagi T, Kato M, Sanada M, Weiss T, Haferlach C, Dugas M, Ruckert C, Haferlach T, Koeffler HP (2010) Genomic profiling of adult acute lymphoblastic leukemia by single nucleotide polymorphism oligonucleotide microarray and comparison to pediatric acute lymphoblastic leukemia. Haematologica 95(9):1481–1488.  https://doi.org/10.3324/haematol.2009.011114CrossRefPubMedPubMedCentralGoogle Scholar
  80. Oneda B, Baldinger R, Reissmann R, Reshetnikova I, Krejci P, Masood R, Ochsenbein-Kölble N, Bartholdi D, Steindl K, Morotti D, Faranda M, Baumer A, Asadollahi R, Joset P, Niedrist D, Breymann C, Hebisch G, Hüsler M, Mueller R, Prentl E, Wisser J, Zimmermann R, Rauch A (2014) High-resolution chromosomal microarrays in prenatal diagnosis significantly increase diagnostic power. Prenat Diagn 34(6):525–533.  https://doi.org/10.1002/pd.4342CrossRefPubMedPubMedCentralGoogle Scholar
  81. Ouillette P, Collins R, Shakhan S, Li J, Peres E, Kujawski L, Talpaz M, Kaminski M, Li C, Shedden K, Malek SN (2011) Acquired genomic copy number aberrations and survival in chronic lymphocytic leukemia. Blood 118(11):3051–3061.  https://doi.org/10.1182/blood-2010-12-327858CrossRefPubMedPubMedCentralGoogle Scholar
  82. Papenhausen P, Schwartz S, Risheg H, Keitges E, Gadi I, Burnside RD, Jaswaney V, Pappas J, Pasion R, Friedman K, Tepperberg J (2011) UPD detection using homozygosity profiling with a SNP genotyping microarray. Am J Med Genet A 155A(4):757–768.  https://doi.org/10.1002/ajmg.a.33939CrossRefPubMedPubMedCentralGoogle Scholar
  83. Paxton CN, Rowe LR, South ST (2015) Observation of the genomic landscape beyond 1p19q deletions and EGFR amplification in glioma. Mol Cytogenet 8:60.  https://doi.org/10.1186/s13039-015-0156-1. eCollection 2015CrossRefPubMedPubMedCentralGoogle Scholar
  84. Peterson JF, Van Dyke DL, Hoppman NL, Kearney HM, Sukov WR, Greipp PT, Ketterling RP, Baughn LB (2018) The utilization of chromosomal microarray technologies for hematologic neoplasms: an ACLPS critical review. Am J Clin Pathol 150(5):375–384.  https://doi.org/10.1093/ajcp/aqy076CrossRefPubMedPubMedCentralGoogle Scholar
  85. Piard J, Philippe C, Marvier M, Beneteau C, Roth V, Valduga M, Béri M, Bonnet C, Grégoire MJ, Jonveaux P, Leheup B (2010) Clinical and molecular characterization of a large family with an interstitial 15q11q13 duplication. Am J Med Genet A 152A(8):1933–1941.  https://doi.org/10.1002/ajmg.a.33521CrossRefPubMedPubMedCentralGoogle Scholar
  86. Pichert G, Mohammed SN, Ahn JW, Ogilvie CM, Izatt L (2011) Unexpected findings in cancer predisposition genes detected by array comparative genomic hybridization: what are the issues? J Med Genet 48(8):535–539.  https://doi.org/10.1136/jmg.2010.087593CrossRefPubMedPubMedCentralGoogle Scholar
  87. Rauch A, Rüschendorf F, Huang J, Trautmann U, Becker C, Thiel C, Jones KW, Reis A, Nürnberg P (2004) Molecular karyotyping using an SNP array for genome wide genotyping. J Med Genet 41:916–922.  https://doi.org/10.1136/jmg.2004.022855CrossRefPubMedPubMedCentralGoogle Scholar
  88. Rosenfeld JA, Coe BP, Eichler EE, Cuckle H, Shaffer LG (2013) Estimates of penetrance for recurrent pathogenic copy-number variations. Genet Med 15(6):478–481.  https://doi.org/10.1038/gim.2012.164CrossRefPubMedGoogle Scholar
  89. Sagoo GS, Butterworth AS, Sanderson S, Shaw-Smith C, Higgins JP, Burton H (2009) Array CGH in patients with learning disability (mental retardation) and congenital anomalies: updated systematic review and meta-analysis of 19 studies and 13,926 subjects. Genet Med 11(3):139–146.  https://doi.org/10.1097/GIM.0b013e318194ee8fCrossRefPubMedPubMedCentralGoogle Scholar
  90. Sanders SJ, Ercan-Sencicek AG, Hus V, Luo R, Murtha MT, Moreno-De-Luca D, Chu SH, Moreau MP, Gupta AR, Thomson SA, Mason CE, Bilguvar K, Celestino-Soper PB, Choi M, Crawford EL, Davis L, Wright NR, Dhodapkar RM, DiCola M, DiLullo NM, Fernandez TV, Fielding-Singh V, Fishman DO, Frahm S, Garagaloyan R, Goh GS, Kammela S, Klei L, Lowe JK, Lund SC, McGrew AD, Meyer KA, Moffat WJ, Murdoch JD, O’Roak BJ, Ober GT, Pottenger RS, Raubeson MJ, Song Y, Wang Q, Yaspan BL, Yu TW, Yurkiewicz IR, Beaudet AL, Cantor RM, Curland M, Grice DE, Günel M, Lifton RP, Mane SM, Martin DM, Shaw CA, Sheldon M, Tischfield JA, Walsh CA, Morrow EM, Ledbetter DH, Fombonne E, Lord C, Martin CL, Brooks AI, Sutcliffe JS, Cook EH Jr, Geschwind D, Roeder K, Devlin B, State MW (2011) Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron 70(5):863–885.  https://doi.org/10.1016/j.neuron.2011.05.002CrossRefPubMedPubMedCentralGoogle Scholar
  91. Schoumans J, Suela J, Hastings R, Muehlematter D, Rack K, van den Berg E, Berna Beverloo H, Stevens-Kroef M (2016) Guidelines for genomic array analysis in acquired haematological neoplastic disorders. Genes Chromosomes Cancer 55(5):480–491.  https://doi.org/10.1002/gcc.22350CrossRefPubMedPubMedCentralGoogle Scholar
  92. Shaffer LG, Kashork CD, Saleki R, Rorem E, Sundin K, Ballif BC, Bejjani BA (2006) Targeted genomic microarray analysis for identification of chromosome abnormalities in 1500 consecutive clinical cases. J Pediatr 149(4):98–102.  https://doi.org/10.1016/j.jpeds.2006.02.006CrossRefPubMedPubMedCentralGoogle Scholar
  93. Shaffer LG, Rosenfeld JA, Dabell MP, Coppinger J, Bandholz AM, Ellison JW, Ravnan JB, Torchia BS, Ballif BC, Fisher AJ (2012) Detection rates of clinically significant genomic alterations by microarray analysis for specific anomalies detected by ultrasound. Prenat Diagn 32(10):986–995.  https://doi.org/10.1002/pd.3943CrossRefPubMedPubMedCentralGoogle Scholar
  94. Shanske AL, Edelmann L, Kardon NB, Gosset P, Levy B (2004) Detection of an interstitial deletion of 2q21-22 by high resolution comparative genomic hybridization in a child with multiple congenital anomalies and an apparent balanced translocation. Am J Med Genet A 131(1):29–35.  https://doi.org/10.1002/ajmg.a.30311CrossRefPubMedPubMedCentralGoogle Scholar
  95. Sharp AJ, Hansen S, Selzer RR, Cheng Z, Regan R, Hurst JA, Stewart H, Price SM, Blair E, Hennekam RC, Fitzpatrick CA, Segraves R, Richmond TA, Guiver C, Albertson DG, Pinkel D, Eis PS, Schwartz S, Knight SJ, Eichler EE (2006) Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome. Nat Genet 38(9):1038–1042PubMedCrossRefPubMedCentralGoogle Scholar
  96. Sharp AJ, Selzer RR, Veltman JA, Gimelli S, Gimelli G, Striano P, Coppola A, Regan R, Price SM, Knoers NV, Eis PS, Brunner HG, Hennekam RC, Knight SJ, de Vries BB, Zuffardi O, Eichler EE (2007) Characterization of a recurrent 15q24 microdeletion syndrome. Hum Mol Genet 16(5):567–572.  https://doi.org/10.1093/hmg/ddm016CrossRefPubMedPubMedCentralGoogle Scholar
  97. Sharp AJ, Mefford HC, Li K, Baker C, Skinner C, Stevenson RE, Schroer RJ, Novara F, De Gregori M, Ciccone R, Broomer A, Casuga I, Wang Y, Xiao C, Barbacioru C, Gimelli G, Bernardina BD, Torniero C, Giorda R, Regan R, Murday V, Mansour S, Fichera M, Castiglia L, Failla P, Ventura M, Jiang Z, Cooper GM, Knight SJ, Romano C, Zuffardi O, Chen C, Schwartz CE, Eichler EE (2008) A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures. Nat Genet 40:322–328.  https://doi.org/10.1038/ng.93CrossRefPubMedPubMedCentralGoogle Scholar
  98. Shaw-Smith C, Pittman AM, Willatt L, Martin H, Rickman L, Gribble S, Curley R, Cumming S, Dunn C, Kalaitzopoulos D, Porter K, Prigmore E, Krepischi-Santos AC, Varela MC, Koiffmann CP, Lees AJ, Rosenberg C, Firth HV, de Silva R, Carter NP (2006) Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability. Nat Genet 38(9):1032–1037.  https://doi.org/10.1038/ng1858CrossRefPubMedPubMedCentralGoogle Scholar
  99. Shevell M, Ashwal S, Donley D, Flint J, Gingold M, Hirtz D, Majnemer A, Noetzel M, Sheth RD, Quality Standards Subcommittee of the American Academy of Neurology, Practice Committee of the Child Neurology Society (2003) Practice parameter: evaluation of the child with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and The Practice Committee of the Child Neurology Society. Neurology 60(3):367–380PubMedCrossRefPubMedCentralGoogle Scholar
  100. Simons A, Sikkema-Raddatz B, de Leeuw N, Konrad NC, Hastings RJ, Schoumans J (2012) Genome-wide arrays in routine diagnostics of hematological malignancies. Hum Mutat 33(6):941–948.  https://doi.org/10.1002/humu.22057CrossRefPubMedPubMedCentralGoogle Scholar
  101. Simovich MJ, Yatsenko SA, Kang SH, Cheung SW, Dudek ME, Pursley A, Ward PA, Patel A, Lupski JR (2007) Prenatal diagnosis of a 9q34.3 microdeletion by array-CGH in a fetus with an apparently balanced translocation. Prenat Diagn 27(12):1112–1117.  https://doi.org/10.1002/pd.1841CrossRefPubMedPubMedCentralGoogle Scholar
  102. Sismani C, Kitsiou-Tzeli S, Ioannides M (2008) Cryptic genomic imbalances in patients with de novo or familial apparently balanced translocations and abnormal phenotype. Mol Cytogenet 1:15PubMedPubMedCentralCrossRefGoogle Scholar
  103. Slovak ML, Bedell V, Hsu YH, Estrine DB, Nowak NJ, Delioukina ML, Weiss LM, Smith DD, Forman SJ (2011) Molecular karyotypes of Hodgkin and Reed-Sternberg cells at disease onset reveal distinct copy number alterations in chemosensitive versus refractory Hodgkin lymphoma. Clin Cancer Res 17(10):3443–3454.  https://doi.org/10.1158/1078-0432.CCR-10-1071CrossRefPubMedPubMedCentralGoogle Scholar
  104. Society for Maternal-Fetal Medicine (SMFM), Dugoff L, Norton ME, Kuller JA (2015) The use of chromosomal microarray for prenatal diagnosis. Society for Maternal-Fetal Medicine (SMFM) Consult Series I #41. Am J Obstet Gynecol 215(4):B2–B9.  https://doi.org/10.1016/j.ajog.2016.07.016CrossRefGoogle Scholar
  105. Song Q, Peng M, Chu Y, Huang S (2017) Techniques for detecting chromosomal aberrations in myelodysplastic syndromes. Oncotarget 8(37):62716–62729.  https://doi.org/10.18632/oncotarget.17698CrossRefPubMedPubMedCentralGoogle Scholar
  106. South ST, Lee C, Lamb AN, Higgins AW, Kearney HM (2013) Working Group for the American College of Medical Genetics and Genomics Laboratory Quality Assurance Committee. ACMG Standards and Guidelines for constitutional cytogenomic microarray analysis, including postnatal and prenatal applications: revision 2013. Genet Med 15:901–909PubMedCrossRefPubMedCentralGoogle Scholar
  107. Srebniak MI, Joosten M, Knapen MFCM, Arends LR, Polak M, van Veen S, Go ATJI, Van Opstal D (2018) Frequency of submicroscopic chromosomal aberrations in pregnancies without increased risk for structural chromosomal aberrations: systematic review and meta-analysis. Ultrasound Obstet Gynecol 51(4):445–452.  https://doi.org/10.1002/uog.17533CrossRefPubMedPubMedCentralGoogle Scholar
  108. Stefansson H, Rujescu D, Cichon S, Pietiläinen OP, Ingason A, Steinberg S, Fossdal R, Sigurdsson E, Sigmundsson T, Buizer-Voskamp JE, Hansen T, Jakobsen KD, Muglia P, Francks C, Matthews PM, Gylfason A, Halldorsson BV, Gudbjartsson D, Thorgeirsson TE, Sigurdsson A, Jonasdottir A, Jonasdottir A, Bjornsson A, Mattiasdottir S, Blondal T, Haraldsson M, Magnusdottir BB, Giegling I, Möller HJ, Hartmann A, Shianna KV, Ge D, Need AC, Crombie C, Fraser G, Walker N, Lonnqvist J, Suvisaari J, Tuulio-Henriksson A, Paunio T, Toulopoulou T, Bramon E, Di Forti M, Murray R, Ruggeri M, Vassos E, Tosato S, Walshe M, Li T, Vasilescu C, Mühleisen TW, Wang AG, Ullum H, Djurovic S, Melle I, Olesen J, Kiemeney LA, Franke B, GROUP, Sabatti C, Freimer NB, Gulcher JR, Thorsteinsdottir U, Kong A, Andreassen OA, Ophoff RA, Georgi A, Rietschel M, Werge T, Petursson H, Goldstein DB, Nöthen MM, Peltonen L, Collier DA, St Clair D, Stefansson K (2008) Large recurrent microdeletions associated with schizophrenia. Nature 455(7210):232–236.  https://doi.org/10.1038/nature07229CrossRefGoogle Scholar
  109. Stevens-Kroef M, Weghuis DO, Croockewit S (2012) High detection rate of clinically relevant genomic abnormalities in plasma cells enriched from patients with multiple myeloma. Genes Chromosomes Cancer 51(11):997–1006PubMedCrossRefGoogle Scholar
  110. Stevens-Kroef M, Weghuis DO, Wezenberg S, Croockewit S, Wessels H, van der Mespel M, Zweegman S, Poddighe PJ (2016) Superior identification of prognostic relevant copy number abnormalities by SNP-based genomic arrays as compared to interphase FISH in multiple myeloma. Blood 128:4426CrossRefGoogle Scholar
  111. Stevens-Kroef MJ, Olde Weghuis D, ElIdrissi-Zaynoun N, van der Reijden B, Cremers EMP, Alhan C, Westers TM, Visser-Wisselaar HA, Chitu DA, Cunha SM, Vellenga E, Klein SK, Wijermans P, de Greef GE, Schaafsma MR, Muus P, Ossenkoppele GJ, van de Loosdrecht AA, Jansen JH (2017) Genomic array as compared to karyotyping in myelodysplastic syndromes in a prospective clinical trial. Genes Chromosomes Cancer 56(7):524–534.  https://doi.org/10.1002/gcc.22455CrossRefPubMedGoogle Scholar
  112. Stewart LR, Hall AL, Kang SH, Shaw CA, Beaudet AL (2011) High frequency of known copy number abnormalities and maternal duplication 15q11-q13 in patients with combined schizophrenia and epilepsy. BMC Med Genet 12:154.  https://doi.org/10.1186/1471-2350-12-154CrossRefPubMedPubMedCentralGoogle Scholar
  113. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J (2017) WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th ed. World Health Organization; International Agency for Research on Cancer, Lyon. ISBN:9789283244943; 9781234567897 NLM ID: 101716000Google Scholar
  114. Tabet AC, Verloes A, Pilorge M, Delaby E, Delorme R, Nygren G, Devillard F, Gérard M, Passemard S, Héron D, Siffroi JP, Jacquette A, Delahaye A, Perrin L, Dupont C, Aboura A, Bitoun P, Coleman M, Leboyer M, Gillberg C, Benzacken B, Betancur C (2015) Complex nature of apparently balanced chromosomal rearrangements in patients with autism spectrum disorder. Mol Autism 6:19.  https://doi.org/10.1186/s13229-015-0015-2. eCollection 2015CrossRefPubMedPubMedCentralGoogle Scholar
  115. Taylor J, Xiao W, Abdel-Wahab O (2017) Diagnosis and classification of hematologic malignancies on the basis of genetics. Blood 130(4):410–423.  https://doi.org/10.1182/blood-2017-02-734541CrossRefPubMedPubMedCentralGoogle Scholar
  116. Thiel A, Beier M, Ingenhag D, Servan K, Hein M, Moeller V, Betz B, Hildebrandt B, Evers C, Germing U, Royer-Pokora B (2011) Comprehensive array CGH of normal karyotype myelodysplastic syndromes reveals hidden recurrent and individual genomic copy number alterations with prognostic relevance. Leukemia:387–399.  https://doi.org/10.1038/leu.2010.293PubMedCrossRefGoogle Scholar
  117. van Bon BW, Mefford HC, Menten B, Koolen DA, Sharp AJ, Nillesen WM, Innis JW, de Ravel TJ, Mercer CL, Fichera M, Stewart H, Connell LE, Ounap K, Lachlan K, Castle B, Van der Aa N, van Ravenswaaij C, Nobrega MA, Serra-Juhé C, Simonic I, de Leeuw N, Pfundt R, Bongers EM, Baker C, Finnemore P, Huang S, Maloney VK, Crolla JA, van Kalmthout M, Elia M, Vandeweyer G, Fryns JP, Janssens S, Foulds N, Reitano S, Smith K, Parkel S, Loeys B, Woods CG, Oostra A, Speleman F, Pereira AC, Kurg A, Willatt L, Knight SJ, Vermeesch JR, Romano C, Barber JC, Mortier G, Pérez-Jurado LA, Kooy F, Brunner HG, Eichler EE, Kleefstra T, de Vries BB (2009) Further delineation of the 15q13 microdeletion and duplication syndromes: a clinical spectrum varying from non-pathogenic to a severe outcome. J Med Genet 46(8):511–523.  https://doi.org/10.1136/jmg.2008.063412CrossRefPubMedPubMedCentralGoogle Scholar
  118. Van Opstal D, de Vries F, Govaerts L, Boter M, Lont D, van Veen S, Joosten M, Diderich K, Galjaard RJ, Srebniak MI (2015) Benefits and burdens of using a SNP array in pregnancies at increased risk for the common aneuploidies. Hum Mutat 36(3):319–326.  https://doi.org/10.1002/humu.22742CrossRefPubMedGoogle Scholar
  119. Vanakker O, Vilain C, Janssens K, Van der Aa N, Smits G, Bandelier C, Blaumeiser B, Bulk S, Caberg JH, De Leener A, De Rademaeker M, de Ravel T, Desir J, Destree A, Dheedene A, Gaillez S, Grisart B, Hellin AC, Janssens S, Keymolen K, Menten B, Pichon B, Ravoet M, Revencu N, Rombout S, Staessens C, Van Den Bogaert A, Van Den Bogaert K, Vermeesch JR, Kooy F, Sznajer Y, Devriendt K (2014) Implementation of genomic arrays in prenatal diagnosis: the Belgian approach tomeet the challenges. Eur J Med Genet 57(4):151–156.  https://doi.org/10.1016/j.ejmg.2014.02.002CrossRefPubMedPubMedCentralGoogle Scholar
  120. Vermeesch JR, Rauch A (2006) Reply to Hochstenbach et al. ‘Molecular karyotyping’. Eur J Hum Genet 14:1063–1064PubMedCrossRefPubMedCentralGoogle Scholar
  121. Vermeesch JR, Fiegler H, de Leeuw N, Szuhai K, Schoumans J, Ciccone R, Speleman F, Rauch A, Clayton-Smith J, Van Ravenswaaij C, Sanlaville D, Patsalis PC, Firth H, Devriendt K, Zuffardi O (2007) Guidelines for molecular karyotyping in constitutional genetic diagnosis. Eur J Hum Genet 15(11):1105–1114.  https://doi.org/10.1038/sj.ejhg.5201896CrossRefPubMedPubMedCentralGoogle Scholar
  122. Walser SA, Werner-Lin A, Russell A, Wapner RJ, Bernhardt BA (2016) “Something extra on chromosome 5”: Parents’ understanding of positive prenatal chromosomal microarray analysis (CMA) results. J Genet Couns 25(5):1116–1126.  https://doi.org/10.1007/s10897-016-9943-zCrossRefPubMedPubMedCentralGoogle Scholar
  123. Wang Y, Moorhead M, Karlin-Neumann G, Falkowski M, Chen C, Siddiqui F, Davis RW, Willis TD, Faham M (2005) Allele quantification using molecular inversion probes (MIP). Nucleic Acids Res 33(21):e183.  https://doi.org/10.1093/nar/gni177CrossRefPubMedPubMedCentralGoogle Scholar
  124. Wapner RJ, Martin CL, Levy B, Ballif BC, Eng CM, Zachary JM, Savage M, Platt LD, Saltzman D, Grobman WA, Klugman S, Scholl T, Simpson JL, McCall K, Aggarwal VS, Bunke B, Nahum O, Patel A, Lamb AN, Thom EA, Beaudet AL, Ledbetter DH, Shaffer LG, Jackson L (2012) Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med 367(23):2175–2184.  https://doi.org/10.1056/NEJMoa1203382CrossRefPubMedPubMedCentralGoogle Scholar
  125. Wapner RJ, Zachary J, Clifton R (2015) Change in classification of prenatal microarray analysis copy number variants over time. Prenat Diagn 35(Suppl S1):8–3Google Scholar
  126. Werner-Lin A, McCoyd JLM, Bernhardt BA (2016) Balancing genetics (science) and counseling (art) in prenatal chromosomal microarray testing. J Genet Couns 5:855–867CrossRefGoogle Scholar
  127. Westerfield L, Darilek S, van den Veyver I (2014) Counseling challenges with variants of uncertain significance and incidental findings in prenatal genetic screening and diagnosis. J Clin Med 3:1018–1032PubMedPubMedCentralCrossRefGoogle Scholar
  128. Williams J 3rd, Rad S, Beauchamp S, Ratousi D, Subramaniam V, Farivar S, Pisarska MD (2015) Utilization of noninvasive prenatal testing: impact on referrals for diagnostic testing. Am J Obstet Gynecol 213(1):102.e1–102.e6.  https://doi.org/10.1016/j.ajog.2015.04.005CrossRefGoogle Scholar
  129. Wou K, Levy B, Wapner RJ (2016) Chromosomal microarrays for the prenatal detection of microdeletions and microduplications. Clin Lab Med 36(2):261–276.  https://doi.org/10.1016/j.cll.2016.01.017CrossRefPubMedGoogle Scholar
  130. Zhang H, Lu X, Beasley J, Mulvihill JJ, Liu R, Li S, Lee JY (2011) Reversed clinical phenotype due to a microduplication of Sotos syndrome region detected by array CGH: microcephaly, developmental delay and delayed bone age. Am J Med Genet A 155A(6):1374–1378.  https://doi.org/10.1002/ajmg.a.33769CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Cytogenetics Laboratory, Department of Pathology and Laboratory MedicineWeill Cornell MedicineNew YorkUSA

Personalised recommendations