This quarter we talk to Nicole Bain (MHGSA), SeniorScientist – Cytogenetics from Hunter Area PathologyService, New South Wales Australia

Q. Could you tell us a bit about your work history?I started out in research looking at tissue specific geneexpression patterns using RNA in-situ hybridisation: ofcourse now you would just use expression arrays. I movedinto diagnostic cytogenetics in 2001 with a keen interest inmolecular cytogenetics. In our laboratory I have been heavilyinvolved in the implementation of array technology as firstline testing for postnatal referrals of developmental delay and intellectual handicap. We are starting to get into prenatalsamples, however I believe you need to establish a goodlevel of experience in the array platform on postnatalsamples before venturing into the prenatal setting.

How long have you been running BlueGnome’splatform?We first started using BlueGnome’s Cytochip platform in2006-2007 on 1Mb BAC arrays. In 2007 we performedapproximately 40 postnatal arrays, this number has steadilyincreased to approximately 1400 postnatal cases in 2011,and nearly 200 foetal demise samples in 2011.

You mentioned that you’re starting to use prenatalsamples, which prenatal referrals are you considering for investigation on the arrays?We are currently running a pilot study to investigate howbest to implement array testing in the prenatal setting.Currently the prenatal microarray pilot study is restricted to referrals with foetal abnormality on ultrasound or MRI.Referrals for increased risk by triple screen test, AMA,patient anxiety, increased NT are not recommended formicroarray at this time.

Why did you feel the need to develop a specific designfor prenatal cases and not simply use the ISCA array? The ISCA design is targeted for referrals of developmentaldelay and intellectual handicap, as yet there is no ISCAconsensus on what should be put on a prenatal array.

There were two main things to consider in the design of the array, firstly what information did we want from the array and secondly how did we want our array to performtechnically. In our case, consultation and discussion with our clinicians led to the decision to remove some of theregions (currently on the ISCA design) which may causeadditional patient anxiety and are unlikely to be relevant to the current clinical presentation for example genesassociated with late onset diseases.

From a technical perspective we wanted the array to be as robust as possible and try to limit the number of single probe calls due to technical artefacts. To do thiswe consulted with BlueGnome for a loose backbone of duplicated probes to ensure an accurate result and to eliminate single probe noise, and increased density ofprobes in regions of known significance. Of course our

Interview with Nicole Bain

ideas about what should be on a prenatal will likely change as more labs start implementing the technology on prenatalreferrals.

How are you planning to report variants of unknownsignificance (VOUS) – what procedures do you have inplace for counselling patients in this event?VOUS are an inevitable fact of performing arrays. Pre-testcounselling needs to spell out the possibility that they mayarise. Parental samples must accompany the prenatal sampleso they can be tested to determine whether the VOUS isfamilial or not.

Are you planning to culture samples or are you usingdirectly extracted DNA samples?At the moment we are using cultured cells, but eventually we plan to use uncultured samples.

CytoChip Focus publications can be found in our new publications booklet:

http://www.cambridgebluegnome.com/uploads/assets/publics/3499/original/CytoChip_Focus_pub_booklet_May_2012.pdf?1339423349

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