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Download A deletion was detected on CGH microarray. The ISCN (2009)
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Deciphering the Prenatal Microarray Alan Ma O&G Meeting 12th November 2014 Aims • • • • • Role of microarray in prenatal testing How we decipher the microarray results Common scenarios Unrelated/incidental findings of significance Future directions 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) There are… • 20 000 nuclear genes/genome • 5000 OMIM-listed with known disease-related phenotypes • 15 000 uncertain/experimental phenotypes Chromosomal Microarray Chromosomal Microarray CMA vs karyotype Array • 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 10-400kb • Hi-res arrays can pick up single gene CNVs • Will also pick VOUS in 2-4% of cases Karyotype • Pickup 3-4% • Resolution 5-10Mb • Will pickup balanced translocations and structural rearrangements 60K Agilent Array Can you spot the deletion? Can you spot the deletion? Can you spot the deletion? Normal copy of 9 Deleted copy of 9 Array: reported as 7.3Mb deletion in 9q22 Benefits and disadvantages Benefits • Higher yield • Genome-wide • Delineates deletions/ duplications more clearly – ‘what genes are in there?’ = more precise answer Disadvantages • 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 Neonatal consult • Respiratory distress • Nasal piriform aperture stenosis • Hypoteloric and hypotonic 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 p11.31. 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. 2 ways to analyse this USCS Genome Browser http://genome.ucsc.edu/ • Free to use • Data-overload Decipher Database https://decipher.sanger.ac.uk/index • Curated database of CNVs (Wellcome Sanger) • Need membership (easy) USCS Genome Browser Type in Coordinates A deletion was detected on CGH microarray.TheISCN (2009) description is:arr 18p11.32p11.31(138,963-6,963,069)x1 Type in Coordinates A deletion was detected on CGH microarray.TheISCN (2009) description is:arr 18p11.32p11.31(138,963-6,963,069)x1 You can customise Decipher is easier Links to OMIM