Investigating abnormal babies using DNA sequencing - a new approach
Research type
Research Study
Full title
Alternatives to microarrays:evaluating fetal structural abnormalities using copy number variation by sequencing (CNV-Seq)
IRAS ID
194006
Contact name
Kelly Cohen
Contact email
Sponsor organisation
Leeds Teaching Hospitals Trust
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Around 2-3% of babies have abnormalities detected during antenatal scans. Some of these babies will have an underlying problem with their genetic make-up. Some genetic changes are large, and easily seen by conventional testing (karyotyping). Recently newer tests have become available which can detect much smaller genetic changes, in particular a test called array comparative genomic hybridisation or array CGH. An exact diagnosis allows parents to be counselled much more clearly, and helps clinicians give information about effects on the baby. Parents may then wish to make different reproductive choices.
Array CGH detects up to an extra 10% of genetic problems compared to karyotyping, but can be technically challenging when tiny samples of DNA are obtained from prenatal tests like amniocentesis. The tissue we obtain from inside the womb is not as easy to test as blood tests taken after birth, and sometimes the array CGH test is of poor quality or fails altogether. In Leeds we have developed a new genetic test called CNV-Seq. This detects small genetic changes in a similar way to array CGH, but uses DNA sequencing to count the changes rather than relying on differences in fluorescent light (as in array CGH).
We have performed a pilot study which suggested that CNV-Seq works well even if the DNA samples from the baby are very poor, and we have already published work which shows it can be as good a test as array CGH in children with developmental problems.
We propose a study to test whether CNV-Seq will detect the same genetic problems as array CGH in babies with abnormalities on ultrasound scans. We will investigate whether the results are more reliable than array CGH, and whether this is a prenatal test which will be useful in the future if standard array CGH testing has failed.
REC name
Yorkshire & The Humber - Bradford Leeds Research Ethics Committee
REC reference
15/YH/0508
Date of REC Opinion
24 Dec 2015
REC opinion
Further Information Favourable Opinion