Table 2

Large-scale CNV studies that reveal common and rare variants associated with ASD

References

Participants

All CNVs (de novo and inherited)

De novo CNVs only

Recurrent de novo or inherited CNVs in cases

Single genes, ASD-associated genes and regions in de novo CNVs found in cases

Sebat et al. 2007 [49]

264 families (AGRE/NIMH), 118 simplex, 47 multiplex, 99 control, 195 cases, 196 controls

Focused on CNVs only

7.2% of cases; 1% of controls; de novo variants larger than 3 Mb: 2.6% of cases; 0.51% of controls

De novo: 2q37.3 (2 del), 3p14.2 (1 dup, 1 del) (cases only)

SLC4A10, FHIT, FLJ16237, A2BP1

Szatmari et al. 2007 [50]

173 families (AGP), multiplex, 196 cases, 292 unaffected sibs

624 total; no significant difference in frequency of CNVs overall in cases and controls. 1.3 CNVs/genome in cases; mean size, 3.4 Mb; 1.27 CNVs/genome in controls; mean size, 4.3 Mb

5.1% of cases, 2.1% of controls

47 CNVs (18 regions) in cases

17p12, 22q11.2, NRXN1

Marshall et al. 2008 [51]

427 families, 237 simplex, 189 multiplex, 427 cases, 500 controls (unrelated), 1,152 additional controls

2,873 total. No significant difference in frequency of CNVs overall in cases and controls. 3.1 CNVs/genome in cases; mean size, 603 kb; 3.1 CNVs/genome in controls (n = 500); mean size, 470 kb

27 ASD cases with de novo variants not found in 1,152 additional controls

983/94 (overlapping CNV/loci) in 427 cases; 31/13 case-only (overlapping CNV/loci) not found in 1,152 additional controls. De novo: 5p15.31-p15.2 (2 del) 7q31.1-q32.2 (2 del) 15q11.2-q13.3 (2 dup) 16p11.2 (1 dup, 2 del)

CDH18, DPYD, NLGN4, DPP6, DLGAP2, ANKRD11, SHANK3

Pinto et al. 2010 [52]

876 families (AGP), simplex/multiplex, 996 cases, 1,752 parents, 1,287 additional controls

5,478 total. 1.19-fold increase in CNVs in cases over controls.1.69 case/control ratio for CNVs ≥ 500 kb. 219 inherited CNVs not in controls and disrupting single genes (DDX53-PTCHD1)

50 out of 876 of ASD cases harbor de novo CNVs. Seven de novo CNVs not in controls and disrupting single genes

NA

SHANK2, SYNGAP1, DLGAP2

Sanders et al. 2011 [21]

1,124 families* (SSC), simplex, 1,124 cases, 2,248 parents, 872 unaffected sibs

No significant difference in frequency of inherited CNVs in cases and controls

Cases (n = 872), controls (n = 872). All de novo CNVs: 5.9% of cases; 1.7% of sibs OR: 3.5. Multigenic de novo CNVs: 4.9% of cases; 0.92% sibs; OR: 5.6. Mean number of genes/CNV 21.4 in cases; 4.6 in sibs. De novo variants larger than 1 Mb: 2.5% cases; 0.5% controls, OR: 5.6

De novo: 1q21.1 (2 dup); 7q11.23 (4 dup); 15q13.2-q13.3 (1 dup/1 del); 16p11.2 (4 dup, 7 del); 16p13.2 (2 dup); 16q23.3 (2 del)

CDH13, USP7, C16orf72

Levy et al. 2011 [20]

887 families (SSC), simplex, 858 cases, 863 unaffected sibs

No significant difference in frequency of inherited CNVs in cases and controls

7.9% in cases (median genes per CNV: 4) 2% in unaffected sibs (median genes per CNV: 0)

De novo: 16p11.2 (4 dup, 6 del); 7q11.23 (2 dup); 16p13.2 (2 dup, 1 del); 12 recurrent loci representing 121 events (data combined with [52])

DDX53-PTCHD1, USP7

*Contains 1,340 overlapping probands and sibs with [20]. Del, deletions; dup, duplications.

Berg and Geschwind Genome Biology 2012 13:247   doi:10.1186/gb-2012-13-7-247