1. Deciphering the Prenatal Microarray
Alan Ma
O&G Meeting
12th November 2014

2. Aims Role of microarray in prenatal testing
How we decipher the microarray results
Common scenarios
Unrelated/incidental findings of significance
Future directions

3. Standard G-banded karyotype
Pickup ~ 3% in congenital abnormalities (MCA)/intellectual disability (ID)
Good for translocations, aneuploidy, large deletions and duplications
Resolution around 5-10Mb
Rapid turnaround 36 hours (QFPCR aneuploidy) to 1 week (full culture)

5. There are…
nuclear genes/genome
5000 OMIM-listed with known disease-related phenotypes
uncertain/experimental phenotypes

6. Chromosomal Microarray

7. Chromosomal Microarray

8. CMA vs karyotype Array Karyotype
Pickup additional 4-6% above G-banded karyotype in prenatal setting of structural abnormality on ultrasound
15% in MCA/ID postnatally
Detects microduplications and deletions not seen on conventional karyotype
Resolution kb
Hi-res arrays can pick up single gene CNVs
Will also pick VOUS in 2-4% of cases
Pickup 3-4%
Resolution 5-10Mb
Will pickup balanced translocations and structural rearrangements

9. 60K Agilent Array

10. Can you spot the deletion?

11. Can you spot the deletion?

12. Can you spot the deletion?

13. Normal copy of 9
Deleted copy of 9
Array: reported as 7.3Mb deletion in 9q22

16. Benefits and disadvantages
Higher yield
Genome-wide
Delineates deletions/ duplications more clearly – ‘what genes are in there?’ = more precise answer
Cannot detect balanced translocations or map imbalances
Misses point mutations and small del/dups < 10kb
Can ‘unmask’ carriers of recessive conditions, unrelated conditions and consanguinuity!
Can be hard to interpret results and counsel - VOUSes
Turnaround time
2 weeks
Longer if issues with DNA quality/quantity, parental studies

17. Neonatal consult Respiratory distress Nasal piriform aperture stenosis
Hypoteloric and hypotonic

19. RESULT: A deletion was detected on CGH microarray
RESULT: A deletion was detected on CGH microarray. The ISCN (2009) description is: arr 18p11.32p11.31(138,963-6,963,069)x1 CONCLUSION: Microarray testing detects a terminal deletion, within chromosome 18 bands p11.32 to p This has minimum size 6.82Mb, and extends from position 0.14 to 6.96Mb. (Max.size is 7.08Mb, from 0 to 7.08). The deletion includes approx. 40 known genes, from ROCK1P1 to LAMA1. Two of these are associated with OMIM-listed disease, namely LPIN2 & TGIF1.

20. 2 ways to analyse this Free to use Data-overload
USCS Genome Browser
Decipher Database
Free to use
Data-overload
Curated database of CNVs (Wellcome Sanger)
Need membership (easy)

21. USCS Genome Browser

22. Type in Coordinates A deletion was detected on CGH microarray
Type in Coordinates A deletion was detected on CGH microarray.The ISCN (2009) description is:arr 18p11.32p11.31(138,963-6,963,069)x1

23. Type in Coordinates A deletion was detected on CGH microarray
Type in Coordinates A deletion was detected on CGH microarray.The ISCN (2009) description is:arr 18p11.32p11.31(138,963-6,963,069)x1

25. You can customise

26. Decipher is easier

29. Links to OMIM