Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities

Melanie Manning, Louanne Hudgins, Professional Practice and Guidelines Committee, Melanie Manning, Louanne Hudgins, Professional Practice and Guidelines Committee

Abstract

Laboratory evaluation of patients with developmental delay/intellectual disability, congenital anomalies, and dysmorphic features has changed significantly in the last several years with the introduction of microarray technologies. Using these techniques, a patient's genome can be examined for gains or losses of genetic material too small to be detected by standard G-banded chromosome studies. This increased resolution of microarray technology over conventional cytogenetic analysis allows for identification of chromosomal imbalances with greater precision, accuracy, and technical sensitivity. A variety of array-based platforms are now available for use in clinical practice, and utilization strategies are evolving. Thus, a review of the utility and limitations of these techniques and recommendations regarding present and future application in the clinical setting are presented in this study.

References

    1. Manning M, Hudgins L. Use of array-based technology in the practice of medical genetics. Genet Med. 2007;9:650–653.
    1. Trask BJ. Human cytogenetics: 46 chromosomes, 46 years and counting. Nat Rev Genet. 2002;3:769–778.
    1. Shaffer LG, Beaudet AL, Brothman AR, et al. Microarray analysis for constitutional cytogenetic abnormalities. Genet Med. 2007;9:654–662.
    1. Pinkel D, Segraves R, Sudar D, et al. High resolution analysis of DNA copy-number variation using comparative genomic hybridization to microarrays. Nat Genet. 1998;20:207–211.
    1. Bejjani BA, Saleki R, Ballif BC, et al. Use of targeted array-based CGH for the clinical diagnosis of chromosomal imbalances: is less more? Am J Med Genet. 2005;134:259–267.
    1. Solinas-Toldo S, Lampel S, Stilgenbauer S, et al. Matrix-based comparative genomic hybridization: biochips to screen for genomic imbalances. Genes Chromosomes Cancer. 1997;20:399–407.
    1. Oostlander AE, Meijer GA, Ylstra B. Microarray-based comparative genomic hybridization and its application in human genetics. Clin Genet. 2004;66:488–495.
    1. Snijders AM, Nowak N, Segraves R, et al. Assembly of microarrays for genome-wide measurements of DNA copy number. Nat Genet. 2001;29:263–264.
    1. Bernardini L, Alesi V, Loddo S, et al. High-resolution SNP arrays in mental retardation diagnostics: how much do we gain? Eur J Hum Genet. 2010;18:178–185.
    1. Tyson C, Harvard C, Locker R, et al. Submicroscopic deletions and duplications in individuals with intellectual disability detected by array-CGH. Am J Med Genet. 2005;139:173–185.
    1. Friedman J, Adam S, Arbour L, et al. Detection of pathogenic copy number variants in children with idiopathic intellectual disability using 500 K SNP array genomic hybridization. BMC Genomics. 2009;10:526.
    1. Moeschler JB, Shevell M. Clinical genetic evaluation of the child with mental retardation or developmental delays. Pediatrics. 2006;117:2304–2316.
    1. Rauch A, Hoyer J, Guth S, et al. Diagnostic yield of various genetic approaches in patients with unexplained developmental delay or mental retardation. Am J Med Genet. 2006;140:2063–2074.
    1. Miller DT, Adam MP, Aradhya S, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2010;86:749–764.
    1. Hochstenbach R, van Binsbergen E, Engelen J, et al. Array analysis and karyotyping: workflow consequences based on a retrospective study of 36,325 patients with idiopathic developmental delay in the Netherlands. Eur J Med Genet. 2009;52:161–169.
    1. Shen Y, Dies KA, Holm IA, et al. Clinical genetic testing for patients with autism spectrum disorders. Pediatrics. 2010;125:e727–e735.
    1. Ullmann R, Turner G, Kirchhoff M, et al. Array CGH identifies reciprocal 16p13.1 duplications and deletions that predispose to autism and/or mental retardation. Hum Mutat. 2007;28:674–682.
    1. Miller DT, Shen Y, Weiss LA, et al. Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders. J Med Genet. 2009;46:242–248.
    1. Sebat J, Lakshmi B, Malhotra D, et al. Strong association of de novo copy number mutations with autism. Science. 2007;316:445–449.
    1. Christian SL, Brune CW, Sudi J, et al. Novel submicroscopic chromosomal abnormalities detected in autism spectrum disorder. Biol Psychiatry. 2008;63:1111–1117.
    1. Edelmann L, Hirschhorn K. Clinical utility of array CGH for the detection of chromosomal imbalances associated with mental retardation and multiple congenital anomalies. Ann NY Acad Sci. 2009;1151:157–166.
    1. Sismani C, Kitsiou-Tzeli S, Ioannides M, et al. Cryptic genomic imbalances in patients with de novo or familial apparently balanced translocations and abnormal phenotype. Mol Cytogenet. 2008;1:15.
    1. Adam MP, Justice AN, Schelley S, et al. Clinical utility of array comparative genomic hybridization: uncovering tumor susceptibility in individuals with developmental delay. J Pediatr. 2009;154:143–146.
    1. Adams SA, Coppinger J, Saitta SC, et al. Impact of genotype-first diagnosis: the detection of microdeletion and microduplication syndromes with cancer predisposition by aCGH. Genet Med. 2009;11:314–322.
    1. Rujescu D, Ingason A, Cichon S, et al. Disruption of the neurexin 1 gene is associated with schizophrenia. Hum Mol Genet. 2009;18:988–996.
    1. Roohi J, Montagna C, Tegay DH, et al. Disruption of contactin 4 in three subjects with autism spectrum disorder. J Med Genet. 2009;46:176–182.
    1. Moeschler JB. Medical genetics diagnostic evaluation of the child with global developmental delay or intellectual disability. Curr Opin Neurol. 2008;21:117–122.
    1. Moeschler JB. Genetic evaluation of intellectual disabilities. Semin Pediatr Neurol. 2008;15:2–9.
    1. Saam J, Gudgeon J, Aston E, et al. How physicians use array comparative genomic hybridization results to guide patient management in children with developmental delay. Genet Med. 2008;10:181–186.
    1. Miller DT, Shen Y, Wu BL. Oligonucleotide microarrays for clinical diagnosis of copy number variation. Curr Protoc Hum Genet. 2008;58:8.12.1–8.12.17.
    1. Shearer BM, Thorland EC, Gonzales PR, et al. Evaluation of a commercially available focused aCGH platform for the detection of constitutional chromosome anomalies. Am J Med Genet. 2007;143A:2357–2370.
    1. Bruno DL, Ganesamoorthy D, Schoumans J, et al. Detection of cryptic pathogenic copy number variations and constitutional loss of heterozygosity using high resolution SNP microarray analysis in 117 patients referred for cytogenetic analysis and impact on clinical practice. J Med Genet. 2009;46:123–131.
    1. McCarroll SA. Extending genome-wide association studies to copy number variation. Hum Mol Genet. 2008;17:R135–R142.
    1. Van Vooren S, Cossens B, De Moor B, et al. Array comparative genomic hybridization and computational genome annotation in constitutional cytogenetics: suggesting candidate genes for novel submicroscopic chromosomal imbalances syndromes. Genet Med. 2007;9:642–649.
    1. Lu X, Shaw CA, Patel A, et al. Clinical implementation of chromosomal microarray analysis: summary of 2513 postnatal cases. PLoS One. 2007;2:e327.
    1. Xiang B, Li A, Valentin D, et al. Analytical and clinical validity of whole-genome oligonucleotide array comparative genomic hybridization for pediatric patients with mental retardation and developmental delay. Am J Med Genet A. 2008;146A:1942–1954.
    1. Stankiewicz P, Beaudet AL. Use of array CGH in the evaluation of dysmorphology, malformations, developmental delay, and idiopathic mental retardation. Curr Opin Genet Dev. 2007;17:182–192.
    1. Scott SA, Cohen N, Brandt T, et al. Detection of low-level mosaicism and placental mosaicism by oligonucleotide array comparative genomic hybridization. Genet Med. 2010;12:85–92.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe