Figure 2

Structure of the SVA elements inserted at the NF1 deletion breakpoints and their source elements. (A) The SVA_F1 element H10_1 spans 4,039 bp and is the likely source element of the SVA copy that inserted within SUZ12P intron 8 in the grandmother of patient DA-77. Starting at its 5′ end, H10_1 comprises a target site duplication (TSD), a transduced sequence (5′TD) and a full-length AluSc from chromosome 9p13.3, a transduced partial exon 1 of MAST2, an Alu-like region, a variable number of tandem repeats (VNTR) region, a SINE-R, a polyA₍₁₇₎ tract, the second TSD, an AluSp element, a second polyA₍₁₇₎ tract and a non-repetitive, unique sequence resulting from a 3′ transduction that harbors two polyadenylation signals (AATAAA). The size of each region is given in basepairs. (B) A copy of the source element H10_1 integrated within SUZ12P intron 8 in the grandmother of patient DA-77. The SVA insertion was associated with a deletion of approximately 1 Mb. The inserted SVA spans 1.7 kb and is 5′ truncated. (C) Structure of the putative source SVA element H6_1084, which spans 2,691 bp and belongs to the SVA_F subfamily. A copy of H6_1084 is presumed to have integrated within SUZ12P intron 8 in patient ASB4-55. Full-length H6_1084 has the following structure starting from the 5′ end: a TSD, a 5′TD from chromosome 12p11.21, a CCCTCT₍₄₎ repeat, a 343-bp Alu-like region, a GC-rich VNTR region, a SINE-R element, two polyadenylation signals, a polyA₍₁₁₎ tract and the second TSD. The length of each region is indicated in basepairs. (D) Structure of the 5′ truncated copy of H6_1084 that has integrated within SUZ12P intron 8 in patient ASB4-55. The SVA insertion was associated with an atypical NF1 deletion of 867 kb. The SVA integration sites within SUZ12P intron 8 demarcate the centromeric breakpoints of the atypical NF1 deletions.