Postnatal SNP Array
Array analysis by SNP array or array CGH will identify copy number changes at a higher resolution than G-banding and will detect microdeletions and microduplications associated with known cytogenetic syndrome regions. In addition, SNP arrays can detect lack of heterozygosity, which in certain chromosomal regions (such as Prader-Willi syndrome) can also be pathogenic. Arrays will not detect balanced rearrangements and have limited sensitivity for the detection of mosaicism.
SNP Array Technical Details
In January 2019, array analysis moved from array CGH to a SNP array platform. The current platform is the whole genome Infinium CytoSNP-850K v1.2 Illumina BeadChip array. The analysis software is BlueFuse Multi giving a backbone resolution of approximately 50 kb (kilobases) and a gene targeted resolution of approximately 10 kb. All reports are currently based on Genome Build GRCh37. Reports do not routinely mention copy number variants considered to be of no clinical significance.
SNP array testing is offered as a first line service for paediatric referrals with:
- Unexplained learning difficulties / developmental delay / behavioural problems (including autism and referrals for the fragile X phenotype).
- Dysmorphism / multiple congenital abnormalities suggestive of a chromosome abnormality.
Professional judgement is used to determine which patients are tested, in line with current lab policy.
Please note: All patients who are eligible for SNP array need to have had this test completed before a referral to Clinical Genetics can be accepted.
The laboratory will require a minimum of 1ml peripheral blood in an EDTA tube (purple top) with a Cytogenetics and DNA joint referral card which you can download from here. Please complete with comprehensive clinical details.
If an EDTA blood sample is not received for a patient an array will not be performed.
The laboratory turnaround times are taken from the ACGS (Association for Clinical Genetic Science) professional best practice guidelines and are as follows:
Proband (no follow up studies required):
95% within 42 calendar days from receipt of a suitable DNA sample.
Parental blood samples requested after detection of imbalance in proband:
95% within 42 calendar days from receipt of suitable parental blood samples and follow-up test material (e.g. FISH probes).
Samples from neonates are prioritised as urgent and the laboratory endeavours to obtain a result within 14 calendar days.
Limits to SNP Array
- SNP array will not detect all genetic abnormalities
- SNP array cannot detect balanced chromosome rearrangements such as reciprocal translocations and inversions. Karyotyping or FISH studies will be carried out for patients suspected of these abnormalities.
- SNP array cannot detect low level mosaicism (< 20% mixture of abnormal and normal cells)
- Anomalies may occur which cannot always be recognised or properly interpreted.
- SNP array cannot detect mutations. Array analysis can detect small genomic imbalances which may disrupt genes and give a similar phenotype to a mutation but it is not sensitive enough to detect mutations within genes. Requests for specific mutation testing can be made to the laboratory (refer to molecular genetics section).
Alternative testing for samples suboptimal for SNP Array
A technique, referred to as CNVseq (Copy Number Variant detection by Sequencing), was introduced into the laboratory in January 2014 to complement array testing. The method uses a Next Generation Sequencing approach to look for copy number variation in the genome in a similar way to SNP array. The technique is used for samples which are considered to be suboptimal for array due to poor quality/low amount of DNA input. These samples are tested by CNVseq instead of array, with the same guidelines for analysis and reporting being applied. Due to the nature of the test, the resolution obtained per case will vary; this will be stated in the report. Please note that the test is currently performed only once every month. As a result, the turnaround times may be slightly higher compared to SNP array.
Fragile X testing
Referrals for patients with a genetically confirmed family history of Fragile X (clinical information of affected family member must be provided) will be tested on request.
Since 1st August 2015, all other samples have array testing performed as a first line test as it has a higher detection rate of causative abnormalities than the Fragile X test. It cannot, however, detect the Fragile X mutation. If following a normal array result Fragile X testing is still required, a newly completed referral form must be sent to the laboratory in order for testing to be initiated.
As SNP array is a whole genome screen there may be occasional unexpected incidental findings which are medically important but unrelated to the specific reasons for referral. It is important to explain to the family that the test is a very detailed look at the whole of the genome and occasionally unexpected incidental findings are detected.
Clinical advice is available from the Department of Clinical Genetics, Chapel Allerton Hospital, Leeds. The team are happy to receive referral letters for patients that have had abnormal array results and/or where there are clinical implications for other family members.
The following test is accredited:
SNP array testing
This test is now accredited to ISO15189 by UKAS.