Editing Comparative genomic hybridization (section)

==History==
The motivation underlying the development of CGH stemmed from the fact that the available forms of cytogenetic analysis at the time ([[giemsa banding]] and [[fluorescence in situ hybridization|FISH]]) were limited in their potential resolution by the microscopes necessary for interpretation of the results they provided. Furthermore, [[giemsa banding]]  interpretation has the potential to be ambiguous and therefore has lowered reliability, and both techniques require high labour inputs which limits the [[locus (genetics)|loci]] which may be examined.<ref name="Pinkel,Albertson" />

The first report of CGH analysis was by Kallioniemi and colleagues in 1992 at the University of California, San Francisco, who utilised CGH in the analysis of solid tumors. They achieved this by the direct application of the technique to both breast cancer cell lines and [[Bladder cancer|primary bladder tumors]] in order to establish complete copy number [[karyotypes]] for the cells. They were able to identify 16 different regions of amplification, many of which were novel discoveries.<ref name="Kallioniemi,Kallioniemi,Sudar,Rutovitz,Gray,Waldman,Pinkel" />

Soon after in 1993, du Manoir et al. reported virtually the same methodology. The authors painted a series of individual human chromosomes from a [[Library (biology)|DNA library]] with two different fluorophores in different proportions to test the technique,  and also applied CGH to genomic [[DNA]] from patients affected with either [[Downs syndrome]] or [[T-cell prolymphocytic leukemia]] as well as cells of a renal papillary carcinoma cell line. It was concluded that the fluorescence ratios obtained were accurate and that differences between genomic DNA from different cell types were detectable, and therefore that CGH was a highly useful cytogenetic analysis tool.<ref>{{cite journal | vauthors = du Manoir S, Speicher MR, Joos S, Schröck E, Popp S, Döhner H, Kovacs G, Robert-Nicoud M, Lichter P, Cremer T | year = 1993 | title = Detection of complete and partial chromosome gains and losses by comparative genomic in situ hybridization | url = http://nbn-resolving.de/urn:nbn:de:bvb:19-epub-9288-3| journal = Human Genetics | volume = 90 | issue = 6| pages = 590–610 | doi=10.1007/bf00202476| pmid = 8444465 | s2cid = 21440368 }}</ref>

Initially, the widespread use of CGH technology was difficult, as protocols were not uniform and therefore inconsistencies arose, especially due to uncertainties in the interpretation of data.<ref name="Weiss,Hermsen,Meijer,VanGrieken,Baak,Kuipers,VanDiest" /> However, in 1994 a review was published which described an easily understood protocol in detail<ref>Kallioniemi OP, Kallioniemi A, Piper J, Isola J, Waldman FM, Gray JW, Pinkel D (1994) Optimizing comparative genomic hybridization for analysis of DNA sequence copy number changes in solid tumors. Genes, Chromosomes and Cancer 10:231–243.</ref> and the image analysis software was made available commercially, which allowed CGH to be utilised all around the world.<ref name="Weiss,Hermsen,Meijer,VanGrieken,Baak,Kuipers,VanDiest" />
As new techniques such as microdissection and [[degeneracy (biology)|degenerate]] [[oligonucleotide]] primed [[polymerase chain reaction]] (DOP-PCR) became available for the generation of DNA products, it was possible to apply the concept of CGH to smaller chromosomal abnormalities, and thus the resolution of CGH was improved.<ref name="Weiss,Hermsen,Meijer,VanGrieken,Baak,Kuipers,VanDiest" />

The implementation of array CGH, whereby [[DNA microarrays]] are used instead of the traditional metaphase chromosome preparation, was pioneered by Solinas-Tolodo et al. in 1997 using tumor cells<ref>Solinas-Toldo S, Lampel S, Stilgenbauer S, Nickolenko J, Benner A, Döhner H, Cremer T, Lichter P (1997) Matrix-based comparative genomic hybridization: biochips to screen for genomic imbalances. Genes, Chromosomes and Cancer 20:399–407.</ref> and Pinkel et al. in 1998 by use of breast cancer cells.<ref>Pinkel D, Segraves R, Sudar D, Clark S, Poole I, Kowbel D, Collins C, Kuo W-L, Chen C, Zhai Y (1998) High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nature genetics 20:207–211.</ref> This was made possible by the [[Human Genome Project]] which generated a library of cloned DNA fragments with known locations throughout the human [[genome]], with these fragments being used as [[hybridization probe|probes]] on the DNA microarray.<ref name="Marquis-Nicholson,Aftimos,Hayes,George,Love">Marquis-Nicholson R, Aftimos S, Hayes I, George A, Love DR (2010) Array comparative genomic hybridization: a new tool in the diagnostic genetic armoury. NZ Med J 123:50–61.</ref> Now probes of various origins such as cDNA, genomic PCR products and [[bacterial artificial chromosome]]s (BACs) can be used on DNA microarrays which may contain up to 2 million probes.<ref name="Marquis-Nicholson,Aftimos,Hayes,George,Love" /> Array CGH is automated, allows greater resolution (down to 100 kb) than traditional CGH as the probes are far smaller than metaphase preparations, requires smaller amounts of DNA, can be targeted to specific chromosomal regions if required and is ordered and therefore faster to analyse, making it far more adaptable to diagnostic uses.<ref name="Marquis-Nicholson,Aftimos,Hayes,George,Love" /><ref>{{cite journal | vauthors = Inazawa J, Inoue J, Imoto I | year = 2004 | title = Comparative genomic hybridization (CGH)-arrays pave the way for identification of novel cancer-related genes | journal = Cancer Science | volume = 95 | issue = 7| pages = 559–563 | doi=10.1111/j.1349-7006.2004.tb02486.x| pmid = 15245590 | s2cid = 33315320 | doi-access = free | pmc = 11158872 }}</ref>

[[Image:CGH schema.jpg|right|thumb|Figure 1. Schematic of CGH protocol]]