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Check it out! Although oligonucleotides do not have the sensitivity to detect single copy changes, averaging of ratios from oligos that map next to each other on the chromosome can compensate for the reduced sensitivity.

There are two approaches to the design of microarrays for CGH applications: whole genome and targeted. Whole genome arrays are designed to cover the entire human genome.

They often include clones that provide an extensive coverage across the genome; and arrays that have contiguous coverage, within the limits of the genome.

Whole-genome arrays have been constructed mostly for research applications and have proven their outstanding worth in gene discovery. They are also very valuable in screening the genome for DNA gains and losses at an unprecedented resolution.

Targeted arrays are designed for a specific region s of the genome for the purpose of evaluating that targeted segment. It may be designed to study a specific chromosome or chromosomal segment or to identify and evaluate specific DNA dosage abnormalities in individuals with suspected microdeletion syndromes or subtelomeric rearrangements.

The crucial goal of a targeted microarray in medical practice is to provide clinically useful results for diagnosis, genetic counseling, prognosis, and clinical management of unbalanced cytogenetic abnormalities.

Conventional CGH has been used mainly for the identification of chromosomal regions that are recurrently lost or gained in tumors, as well as for the diagnosis and prognosis of cancer.

Furthermore, conventional CGH can be used in detecting chromosomal abnormalities and have been shown to be efficient in diagnosing complex abnormalities associated with human genetic disorders.

CGH data from several studies of the same tumor type show consistent patterns of non-random genetic aberrations. For example, gains of chromosomal regions lq, 3q and 8q, as well as losses of 8p, 13q, 16q and 17p, are common to a number of tumor types, such as breast, ovarian, prostate, renal and bladder cancer Figure.

Other alterations, such as 12p and Xp gains in testicular cancer, 13q gain 9q loss in bladder cancer, 14q loss in renal cancer and Xp loss in ovarian cancer are more specific, and might reflect the unique selection forces operating during cancer development in different organs.

Cri du Chat CdC is a syndrome caused by a partial deletion of the short arm of chromosome 5. For example, Levy et al. CGH analysis revealed a loss of chromosomal material from 5p These results demonstrate that conventional CGH is a reliable technique in detecting structural aberrations and, in specific cases, may be more efficient in diagnosing complex abnormalities.

Array CGH applications are mainly directed at detecting genomic abnormalities in cancer. However, array CGH is also suitable for the analysis of DNA copy number aberrations that cause human genetic disorders.

Earlier diagnosis is of benefit to the patient as they may undergo appropriate treatments and counseling to improve their prognosis.

Genetic alterations and rearrangements occur frequently in cancer and contribute to its pathogenesis. Detecting these aberrations by array CGH provides information on the locations of important cancer genes and can have clinical use in diagnosis, cancer classification and prognostification.

In a recent study, array CGH has been implemented to identify regions of chromosomal aberration copy-number variation in several mouse models of breast cancer, leading to identification of cooperating genes during myc-induced oncogenesis.

Array CGH may also be applied not only to the discovery of chromosomal abnormalities in cancer, but also to the monitoring of the progression of tumors.

Differentiation between metastatic and mild lesions is also possible using FISH once the abnormalities have been identified by array CGH.

Prader—Willi syndrome PWS is a paternal structural abnormality involving 15q, while a maternal aberration in the same region causes Angelman syndrome AS.

As a proof of principle Vissers et al. In all three cases, the abnormalities, ranging from 1. When using overlapping microarrays, it is also possible to uncover breakpoints involved in chromosomal aberrations.

Though not yet a widely employed technique, the use of array CGH as a tool for preimplantation genetic screening is becoming an increasingly popular concept.

It has the potential to detect CNVs and aneuploidy in eggs, sperm or embryos which may contribute to failure of the embryo to successfully implant, miscarriage or conditions such as Down syndrome trisomy This makes array CGH a promising tool to reduce the incidence of life altering conditions and improve success rates of IVF attempts.

The technique involves whole genome amplification from a single cell which is then used in the array CGH method.

It may also be used in couples carrying chromosomal translocations such as balanced reciprocal translocations or Robertsonian translocations, which have the potential to cause chromosomal imbalances in their offspring.

A main disadvantage of conventional CGH is its inability to detect structural chromosomal aberrations without copy number changes , such as mosaicism , balanced chromosomal translocations , and inversions.

CGH can also only detect gains and losses relative to the ploidy level. Although CGH has proven to be a useful and reliable technique in the research and diagnostics of both cancer and human genetic disorders, the applications involve only gross abnormalities.

Because of the limited resolution of metaphase chromosomes, aberrations smaller than 5—10 Mb cannot be detected using conventional CGH. Array CGH overcomes many of these limitations.

The standard resolution varies between 1 and 5 Mb, but can be increased up to approximately 40 kb by supplementing the array with extra clones.

However, as in conventional CGH, the main disadvantage of array CGH is its inability to detect aberrations that do not result in copy number changes and is limited in its ability to detect mosaicism.

From Wikipedia, the free encyclopedia. Molecular Pathology — Annu Rev Genom Hum Genet — The move towards array comparative genomic hybridization CGH.

European Journal of Pediatrics — Human Genetics. Genes, Chromosomes and Cancer — Nature genetics — NZ Med J — Cancer Science.

BioMed Research International Nat Genet. Clin Genet — Human Mutation. J Mol Diagn — Drug Discovery Today — Genes Chromosomes Cancer. J Clin Pathol.

J Clin Pathol — Trends Genet. Am J Med Genet. Clin Epigenetics. Prenat Diagn — Am J Hum Genet. Current Opinion in Obstetrics and Gynecology.

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After hybridization, digital imaging systems are used to capture and quantify the relative fluorescence intensities of each of the hybridized fluorophores.

If the intensities of the flurochromes are equal on one probe, this region of the patient's genome is interpreted as having equal quantity of DNA in the test and reference samples; if there is an altered Cy3:Cy5 ratio this indicates a loss or a gain of the patient DNA at that specific genomic region.

Array CGH has been implemented using a wide variety of techniques. Therefore, some of the advantages and limitations of array CGH are dependent on the technique chosen.

The use of BACs provides sufficient intense signals to detect single-copy changes and to locate aberration boundaries accurately. These techniques include ligation -mediated polymerase chain reaction PCR , degenerate primer PCR using one or several sets of primers, and rolling circle amplification.

These arrays currently yield a high spatial resolution, but the number of cDNAs is limited by the genes that are encoded on the chromosomes, and their sensitivity is low due to cross-hybridization.

The amount of oligos is almost infinite, and the processing is rapid, cost-effective, and easy. Although oligonucleotides do not have the sensitivity to detect single copy changes, averaging of ratios from oligos that map next to each other on the chromosome can compensate for the reduced sensitivity.

There are two approaches to the design of microarrays for CGH applications: whole genome and targeted. Whole genome arrays are designed to cover the entire human genome.

They often include clones that provide an extensive coverage across the genome; and arrays that have contiguous coverage, within the limits of the genome.

Whole-genome arrays have been constructed mostly for research applications and have proven their outstanding worth in gene discovery.

They are also very valuable in screening the genome for DNA gains and losses at an unprecedented resolution. Targeted arrays are designed for a specific region s of the genome for the purpose of evaluating that targeted segment.

It may be designed to study a specific chromosome or chromosomal segment or to identify and evaluate specific DNA dosage abnormalities in individuals with suspected microdeletion syndromes or subtelomeric rearrangements.

The crucial goal of a targeted microarray in medical practice is to provide clinically useful results for diagnosis, genetic counseling, prognosis, and clinical management of unbalanced cytogenetic abnormalities.

Conventional CGH has been used mainly for the identification of chromosomal regions that are recurrently lost or gained in tumors, as well as for the diagnosis and prognosis of cancer.

Furthermore, conventional CGH can be used in detecting chromosomal abnormalities and have been shown to be efficient in diagnosing complex abnormalities associated with human genetic disorders.

CGH data from several studies of the same tumor type show consistent patterns of non-random genetic aberrations.

For example, gains of chromosomal regions lq, 3q and 8q, as well as losses of 8p, 13q, 16q and 17p, are common to a number of tumor types, such as breast, ovarian, prostate, renal and bladder cancer Figure.

Other alterations, such as 12p and Xp gains in testicular cancer, 13q gain 9q loss in bladder cancer, 14q loss in renal cancer and Xp loss in ovarian cancer are more specific, and might reflect the unique selection forces operating during cancer development in different organs.

Cri du Chat CdC is a syndrome caused by a partial deletion of the short arm of chromosome 5. For example, Levy et al. CGH analysis revealed a loss of chromosomal material from 5p These results demonstrate that conventional CGH is a reliable technique in detecting structural aberrations and, in specific cases, may be more efficient in diagnosing complex abnormalities.

Array CGH applications are mainly directed at detecting genomic abnormalities in cancer. However, array CGH is also suitable for the analysis of DNA copy number aberrations that cause human genetic disorders.

Earlier diagnosis is of benefit to the patient as they may undergo appropriate treatments and counseling to improve their prognosis. Genetic alterations and rearrangements occur frequently in cancer and contribute to its pathogenesis.

Detecting these aberrations by array CGH provides information on the locations of important cancer genes and can have clinical use in diagnosis, cancer classification and prognostification.

In a recent study, array CGH has been implemented to identify regions of chromosomal aberration copy-number variation in several mouse models of breast cancer, leading to identification of cooperating genes during myc-induced oncogenesis.

Array CGH may also be applied not only to the discovery of chromosomal abnormalities in cancer, but also to the monitoring of the progression of tumors.

Differentiation between metastatic and mild lesions is also possible using FISH once the abnormalities have been identified by array CGH. Prader—Willi syndrome PWS is a paternal structural abnormality involving 15q, while a maternal aberration in the same region causes Angelman syndrome AS.

As a proof of principle Vissers et al. In all three cases, the abnormalities, ranging from 1. When using overlapping microarrays, it is also possible to uncover breakpoints involved in chromosomal aberrations.

Though not yet a widely employed technique, the use of array CGH as a tool for preimplantation genetic screening is becoming an increasingly popular concept.

It has the potential to detect CNVs and aneuploidy in eggs, sperm or embryos which may contribute to failure of the embryo to successfully implant, miscarriage or conditions such as Down syndrome trisomy This makes array CGH a promising tool to reduce the incidence of life altering conditions and improve success rates of IVF attempts.

The technique involves whole genome amplification from a single cell which is then used in the array CGH method.

It may also be used in couples carrying chromosomal translocations such as balanced reciprocal translocations or Robertsonian translocations, which have the potential to cause chromosomal imbalances in their offspring.

A main disadvantage of conventional CGH is its inability to detect structural chromosomal aberrations without copy number changes , such as mosaicism , balanced chromosomal translocations , and inversions.

CGH can also only detect gains and losses relative to the ploidy level. Although CGH has proven to be a useful and reliable technique in the research and diagnostics of both cancer and human genetic disorders, the applications involve only gross abnormalities.

Because of the limited resolution of metaphase chromosomes, aberrations smaller than 5—10 Mb cannot be detected using conventional CGH.

Array CGH overcomes many of these limitations. The standard resolution varies between 1 and 5 Mb, but can be increased up to approximately 40 kb by supplementing the array with extra clones.

However, as in conventional CGH, the main disadvantage of array CGH is its inability to detect aberrations that do not result in copy number changes and is limited in its ability to detect mosaicism.

From Wikipedia, the free encyclopedia. Molecular Pathology — Annu Rev Genom Hum Genet — The move towards array comparative genomic hybridization CGH.

European Journal of Pediatrics — Human Genetics. Genes, Chromosomes and Cancer — Nature genetics — NZ Med J — Cancer Science. BioMed Research International Nat Genet.

Clin Genet — Human Mutation. J Mol Diagn — Drug Discovery Today — Genes Chromosomes Cancer.

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