Table 2.
SRGAP2A and SRGAP2C copy-number variation genotyping of cases and controls
| Genotype method | Size resolution | Cohort1 | Total genotyped | Deletions | Duplications |
|---|---|---|---|---|---|
| SRGAP2A (Cases, N=17,369; Controls, N=10,784) | |||||
| Custom array CGH platforms | >50 kbp | Intellectual disability (Signature Genomics)* (Cooper et al., 2011) | 15,767 | 3 | 3 |
| SNP arrays | >50 kbp | Controls (Cooper et al., 2011) | 8,329 | None | None |
| qPCR2 | >0.5 kbp | Intellectual disability | 1,602 | None | None |
| Controls (NIMH and ClinSeq) | 1,794 | None | None | ||
| Illumina sequencing | >1 kbp | Controls (1000 Genomes Project) | 661 | None | None |
| SRGAP2C (Cases, N=4,475; Controls, N=2,662) | |||||
| qPCR3 | >0.5 kbp | Intellectual disability | 1,602 | None | 1 |
| Controls NIMH and ClinSeq | 1,794 | None | 1 | ||
| Custom Agilent array CGH4 | >300 kbp | Idiopathic autism (SSC) | 2,294 | None | 2 |
| Familial autism (AGRE) | 579 | None | None | ||
| Controls (NIMH and ClinSeq5) | 580 | None | None | ||
| Illumina sequencing | >1 kbp | Controls (1000 Genomes Project | 661 | None | None |
All detected deletions and duplications of SRGAP2A and SRGAP2C were >1 Mbp and include additional genes. Data from the Cooper et al. (2011) study could not be used to assess CNVs for SRGAP2C as there was insufficient probe coverage on the microarrays used in those studies. See also Figure S4 and Table S4 for details of CNV breakpoints, phenotypes, and inheritance status.
Abbreviations: SSC, Simons Simplex Collection (Fischbach and Lord, 2010); AGRE, Autism Genetic Resource Exchange (Geschwind et al., 2001); NIMH, National Institute of Mental Health (https://www.nimhgenetics.org/available_data/controls/); ClinSeq, Clinical Sequencing Pilot Project (Biesecker et al., 2009)
The assay targeted intron 11 of SRGAP2A.
Two assays were used targeting introns 6 and 7 of SRGAP2C, respectively.
Using probes targeting the chromosome 1p11.2 region proximal to SRGAP2C, we identified duplications and determined that a subset of them extended into SRGAP2C by using qPCR assays. Notably, all duplications of SRGAP2C identified from the qPCR assay alone extended into the 1p11.2 proximal region and would have been detected using this same method.
ClinSeq controls (N=373) were screened both with the Agilent array and SRGAP2C qPCR assay.