Flow diagram showing algorithm used for detection of CNVs by use of WGSA with Mapping 100K arrays. HMM = hidden Markov model.

Inherited CNV demonstrated by WGSA with Mapping 100K arrays. A, Plot of t scores for chromosome 2 in father, mother, and child in family 0674, by use of a 21-SNP window. The SNPs are ordered along the X-axis from pter to qter, with the location shown in Mb. The child with MR inherited the CNV (blue oval) from his unaffected father. B, FISH confirmation of the inherited CNV on 2q34. In the father and child, one chromosome 2 (white arrowheads) lacks a signal for probe RP11-93G7, whereas the signal is present on the other chromosome 2 (red arrowheads). In the mother, the signal for probe RP11-93G7 is seen on both chromosomes 2 (red arrowheads).

De novo submicroscopic genomic deletions identified by WGSA with Mapping 100K arrays in the affected child of families 1895, 3476, 4818, 5566, 6545, and 7807. Panels A, C, E, G, I, K, and M show the t scores for each CNV in comparison with the rest of the chromosome, by use of the window size given below. The SNPs are ordered along the X-axis from pter to qter, with the location shown in Mb. Panels B, D, F, H, J, L, and N show FISH confirmation of the CNV in the affected child, by use of the probe given below. The white arrowhead indicates the deleted chromosome without the signal. The red or green arrowhead indicates the normal homologue, which shows the signal. A, Family 1895, chromosome 13, window of 20 SNPs. B, Family 1895, probe RP11-26D3, del(13)(q12.11q12.13). C, Family 3476, chromosome 4, window of 30 SNPs. D, Family 3476, probe RP11-7G22, del(4)(q21.21q22.1). E, Family 4818, chromosome 12, window of 20 SNPs. F, Family 4818, probe RP11-91K23, del(12)(q14.2q15). G, Family 5566, chromosome 14, window of 5 SNPs. The de novo CNV is shown inside the blue oval. H, Family 5566, probe CTD-2136K6, del(14)(q11.2q11.2). I, Family 6545, chromosome 7, window of 20 SNPs. J, Family 6545, probe RP11-802L1, del(7)(p22.2p22.1). K, Family 7807, chromosome 22, window of 20 SNPs. L, Family 7807, probe RP11-79G21, del(22)(q12.1q12.1). M, Family 8326, chromosome 14, window of 20 SNPs. N, Family 8326, probe RP11-340M24, del(14)(q11.2q11.2).

De novo submicroscopic genomic duplication, dup(17)(q21.33q21.33), identified by WGSA with Mapping 100K arrays in family 6168. A, The t scores for each CNV in comparison with the rest of the chromosome, by use of a window size of 8 SNPs. The SNPs are ordered along the X-axis from pter to qter, with the location shown in Mb. The de novo CNV is shown inside the blue oval. B, FISH confirmation of the CNV in the affected child, by use of probes RP11-962N5 (green) and RP11-121F10 (red) in metaphase (left) and interphase (right) cells. In the metaphase spread, the duplication is shown at the red arrowhead, and the normal chromosome is shown at the blue arrowhead. The red signal is duplicated on one chromosome 17; the green signal does not appear duplicated but cross-hybrizes to chromosome 6qter.

A CNV on chromosome 2 in the affected child of family 7551. A, dChip-smoothed copy-number (CN) estimate with a window of 38 SNPs, showing a 1-copy deletion. B, Diagram showing t scores calculated for a sliding window of 38 SNPs that compare the copy number estimated by dChip for SNPs within the window with the copy number estimated for all other SNPs on the same chromosome. The high (negative) t scores associated with the deletion indicate that this deviation in copy number is unlikely to have occurred by chance. In both panels, the X-axis shows the nucleotide position in Mb.

De novo submicroscopic genomic deletion, del(2)(p16.3p16.3), identified by WGSA with Mapping 100K arrays in family 5003. A, The t scores for the CNV in comparison with the rest of the chromosome, by use of a window size of 20 SNPs. The SNPs are ordered along the X-axis from pter to qter, with the location shown in Mb. B, FISH confirmation of the CNV in the affected child by use of probe RP11-1151G3. The white arrowhead indicates the deletion-containing chromosome 2 without the signal. The green arrowhead indicates the normal homologue, which shows the signal.

De novo submicroscopic genomic duplication, dup(16)(p13.3p13.3), identified by WGSA with Mapping 100K arrays in family 4794. A, The t scores for the CNV in comparison with the rest of the chromosome, by use of a window size of 20 SNPs. The SNPs are ordered along the X-axis from pter to qter, with the location shown in Mb. The de novo CNV is shown inside the blue oval. B, FISH confirmation of the CNV in the affected child, by use of probe G248P82513E10 in metaphase cells (left) and probe RP11-397B22 in interphase cells (right). In the metaphase spread, the duplication is indicated by the red arrowhead, and the normal chromosome is indicated by the blue arrowhead. The signal is duplicated on one chromosome 16.