|
Like conventional CGH, array CGH compares fluorescently labeled patient DNA to a differentially labeled control. In conventional CGH, the substrates for analysis are metaphase chromosomes; in array CGH, the patient and control DNA competitively hybridize to thousands of probes representing discrete locations in the human genome that have been immobilized on a glass slide. Also unlike conventional CGH, array CGH can simultaneously measure losses or gains of thousands of submicroscopic regions of the genome; the resolution depends only on the size and space between probes.
Microarray Analysis Studies
The few prospective studies of microarray analysis of prenatal and neonatal samples have shown promising results, with detection of clinically significant abnormalities in 11 percent to 20 percent of neonatal samples in which an abnormality is suspected and 1 percent to 2 percent in prenatal specimens.17,18 Array CGH will likely replace conventional banding for prenatal analysis following abnormal ultrasound results or analysis of the neonate with nonspecific clinical features. Researchers' increased understanding of novel copy-number changes of unclear clinical relevance and the construction of databases to catalogue these abnormalities should mitigate some of the potential for anxiety-provoking test results with this new, information-rich technology.
Pregnancy can be a time of anxiety, particularly if physicians suspect a genetic disorder. These new molecular genetic testing techniques should, if used responsibly, provide timely, comprehensive diagnoses while minimizing parental anxiety.
Aaron Theisen is senior scientific editor, Signature Genomic Laboratories, Spokane, WA.
References
1. Mathews TJ, MacDorman MF. Infant mortality statistics from the 2003 period linked birth/infant death data set. Natl Vital Stat Rep. 2006; 54(16): 1-29.
2. Canfield MA, et al. National estimates and race/ethnic-specific variation of selected birth defects in the United States, 1999-2001. Birth Defects Res A Clin Mol Teratol. 2006; 76(11): 747-56.
3. Hassold T, et al. A cytogenetic study of 1000 spontaneous abortions. Ann Hum Genet. 1980; 44(Pt 2): 151-78.
4. Mansfield ES. Diagnosis of Down syndrome and other aneuploidies using quantitative polymerase chain reaction and small tandem repeat polymorphisms. Hum Mol Genet. 1993; 2(1): 43-50.
5. Schouten JP, et al. Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res. 2002; 30(12): e57.
6. Slater HR, et al. Rapid, high throughput prenatal detection of aneuploidy using a novel quantitative method (MLPA). J Med Genet. 2003; 40(12): 907-12.
7. Gerdes T, et al. Computer-assisted prenatal aneuploidy screening for chromosome 13, 18, 21, X and Y based on multiplex ligation-dependent probe amplification (MLPA). Eur J Hum Genet. 2005; 13(2): 171-5.
8. Hochstenbach R., et al. Rapid detection of chromosomal aneuploidies in uncultured amniocytes by multiplex ligation-dependent probe amplification (MLPA). Prenat Diagn. 2005; 25(11): 1032-9.
9. Amati F, et al. Atypical deletions suggest five 22q11.2 critical regions related to the DiGeorge/velo-cardio-facial syndrome. Eur J Hum Genet. 1999; 7(8): 903-9.
10. Kallioniemi A, et al. Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 1992; 258(5083): 818-21.
11. Kirchhoff M, et al. Deletions below 10 megabasepairs are detected in comparative genomic hybridization by standard reference intervals. Genes Chromosomes Cancer. 1999; 25(4): 410-3.
12. Kirchhoff M, et al. Detection of chromosomal gains and losses in comparative genomic hybridization analysis based on standard reference intervals. Cytometry. 1998; 31(3): 163-73.
13. Lichter P, et al. Comparative genomic hybridization: uses and limitations. Semin Hematol. 2000; 37(4): 348-57.14. Speicher MR, et al. Molecular cytogenetic analysis of formalin-fixed, paraffin-embedded solid tumors by comparative genomic hybridization after universal DNA-amplification. Hum Mol Genet. 1993; 2(11): 1907-14.
15. Pinkel D, et al. High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat Genet. 1998; 20(2): p. 207-11.
16. Solinas-Toldo S, et al. Matrix-based comparative genomic hybridization: biochips to screen for genomic imbalances. Genes Chromosomes Cancer. 1997; 20(4): 399-407.
17. Lu XY, et al. Genomic imbalances in neonates with birth defects: high detection rates by using chromosomal microarray analysis. Pediatrics. 2008; 122(6): 1310-8.
18. Van den Veyver IB, et al. Clinical use of array comparative genomic hybridization (aCGH) for prenatal diagnosis in 300 cases. Prenat Diagn. 2008.
|