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Copy Number and Loss of Heterozygosity Analyses by Affymetrix Genome-Wide SNP Array 6.0 |
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The Genome-Wide SNP array 6.0 contains nearly one million Single Nucleotide Polymprphism (SNP) probes and nearly one million Copy Number Variant (CNV) Probes, providing marker spacing in the range of 3kb. The large number and regular spacing of both types of probes permit the cytogeneticist to define gains and losses of chromosomal segments with greater resolution and precision than standard cytogenetic techniques. Furthermore loss of heterozygosity can be assessed; this is not possible with standard cytogenetic methods. Microarray analysis is an indirect method that measures imbalances between genomes; its inherent limitation is that it cannot detect balanced changes in chromosomal organization. However, since the majority of chromosomal abnormalities that underlie genetic disease involve gains and losses of chromosomal segments, Copy Number Analysis promises to transform the practice of Cytogenetics, by providing higher resolution analysis that is complementary and synergistic when combined with traditional methods
Copy Number Change
The karyotype for GM10636 shows an abnormal X chromosome (on the left).
FISH with probes to the X centromere (DXZ1 green) and to the Steroid Sulfatase Gene in Xp22.32 (STS red) shows a duplication involving the X centromere. This was supported by whole chromosome painting for X (data not shown). One copy of the centromere is inactive.
Together these specify the karotype: 46,X,dup(X)(pter>p11.1::p11.3>qter).ish dup(X)(STS+,DXZ1++,wcpX+).
Copy Number analysis places the duplication from p11.4 through p11.1). Although assigning molecular breakpoints near the centromere is particularly equivocal due to limited coverage the duplicated segment falls between 39.7 and 48.9 megabases from Xpter.
Loss of Hetrozygosity (LOH)
GM14043 shows large regions of heterozygousity on chromosome 2. The log 2 ratio clearly shows diploidy for chromosome 2, but the allele difference shows seven areas without heterozygousity; most involve a few megabases, but the largest is in the range of 50 megabases.
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