Pre- and postnatal genetic testing by array-comparative genomic hybridization: genetic counseling perspectives

Abstract

Recently, a new genetic test has been developed that allows a more detailed examination of the genome when Microarray-based comparative genomic hybridization (CGH microarray) is an evolving technology for the rapid multiplex detection of genomic imbalances. 1 This diagnostic strategy has contributed to our growing understanding of the role of genomic gains and losses in the etiology of genetic disorders. [1][2][3] Microarrays containing large-insert genomic clones can be used to reliably detect deletions or duplications that are tens to hundreds of kilobases in size, well below the level of detection of G-banded karyotype analysis. 4 -7 Recently, arrays consisting of thousands of oligonucleotides distributed throughout the genome have been introduced and have the potential to refine the resolution of gains or losses to an even more detailed level. 8 The genomic clones or oligonucleotides contained in a clinical array generally span most regions that are subject to recurrent deletions and duplications resulting in a recognized syndrome. In addition, they have the potential to detect novel gains or losses that can then be correlated with a clinical phenotype.The addition of CGH microarray to the available diagnostic tools for evaluation of a child or adult suspected of having a genetic condition offers several potential advantages to patients and physicians. The multiplex format of the test permits simultaneous evaluation of multiple disease specific loci and subtelomeric regions, resulting in a more efficient consideration of possible diagnoses and cost savings over ordering testing of each locus individually. As discussed earlier, these tools present the possibility of detecting novel gains or losses that may help characterize a new genomic syndrome. Moreover, with the addition of clones or oligos providing backbone genomic coverage, CGH microarrays have an advantage in terms of sensitivity, cost effectiveness, and higher resolution when compared with a standard karyotype. However, the complexities of the testing, including the availability of various technical platforms and different designs of clinically available arrays, the large number of loci, the broad range of syndromic

Chromosomal microarray analysis as a first-line test in pregnancies with a priori low risk for the detection of submicroscopic chromosomal abnormalities

“…Thus, VOUS identified by prenatal CMA might be approached in a similar manner and managed by providing the patients a thorough pre-test and post-test counselling. 34 This will allow patients to achieve the maximum autonomy and right to information from CMA in order to make informed choices about their pregnancies. 44 Although detection of VOUS cannot be completely excluded with CMA, the growing clinical experience with genome-wide arrays, the increasing availability, sophistication and size of CNV databases (in house or public) for both phenotypically normal and affected individuals, together with parental analysis, allows classification and interpretation for the majority of the alterations discovered, thus substantially reducing the number of VOUS and making CMA increasingly applicable to clinical prenatal diagnosis practice.…”

“…Patients underwent pre-test counseling as described elsewhere, 34 during which the issues that are encountered with CMA were discussed. The couples who accepted evaluation by CMA signed an informed consent form containing a summary of the testing process, potential benefits and limitations of testing, and possible testing outcomes.…”

The ‘thousand-dollar genome’: an ethical exploration

“…The women who rejected the test did so because they were afraid of additional worries, and because they felt the additional conditions that might be found were extremely rare. 68,77,78 Of course, array CGH is not the same thing as a full sequence analysis, but as soon as the costs of whole genome sequencing no longer present a barrier, it is not unlikely that further expansion in that direction will be advocated. Those who want to obtain (and to provide) 'as much information as possible about the foetus' will eventually no longer be happy with anything less than the complete genome.…”

Contemplating effects of genomic structural variation

“…There will be an enhanced role for counselors to communicate the interpreted information to the individuals, families or communities who will be impacted. 52,56 They will be particularly challenged with issues of complexity, subtlety, and uncertainty at the same time as a sheer volume increase in demand for their services. The delivery of information about human variation will be as much an art as a science for a long time to come.…”