Array Flashcards
Databases for array (normal and abnormal)
Normal = database of genomic variants (Dgv)
Abnormal= omim, decipher
, internal standards for cytogenetic arrays (Isca)
Prenatal and postnatal cut offs?
Postnatal 100kb (loss), 500kb gain. Prenatal 1mb, 2mb
Best practice guidelines: to include on report
- description of array
- software
- Genome build
- request follow up if family members
- state risk and if prenatal testing should be offered in the future
- onward referral to genetic counselling
Referral reasons for prenatal array
Ab scan
NT>3.5mm
Specific clinician requests
Family known to carry a clinically significant imbalance
Most important evaluation metrics?
Derivative R spread (DLRSD) <0.3
G-signal2 noise and Rsignal2noise <30
How is hybridisation on an array usually detected?
By flurochrome, silver, chemiluminescence labelled targets
Microarray steps
1) DNA extracted and digested.
2) test DNA labelled red with cy5
3) control DNA green cy3
4) combine equal amounts and hybridise to probes
5) scan
6) image
Types of arrays (6)
1) comparative genomic hybridisation
2) gene expression arrays
3) chromatin immunoprecipitation
4) SNP array
5) exon array (detects different splicing isoforms)
6) fusion gene microarray
What does a filling array detect?
Overlapping probes designed to densely represent a genomic region
BAC arrays?
Used bacterial artificial chromosomes for hybridisation. Resolution 0.5- 1 Mb
Oligo arrays and targeted arrays?
Oligo - custom oligos spotted onto glass
Targeted- designed for a certain area 100-200kb
Limitations of array?
1) can’t detect balanced rearrangements such as reciprocal and inversions
2) may not detect mosaicism if less than 30%
What % of the human genome is CNV?
12%
What % of genome variability is due to cnvs?
7%
Best practice guidelines
BPG
Kearney et al - American college of medical genetics (aCMGh reporting postnatal CNVs)
