Average depth ± SD of sequence coverage across 8q24.3.

<p>Average depth ± SD of sequence coverage across 8q24.3.</p

The breakpoints of disease-associated interchromosomal insertions at Xq27.1 localize near the center of 180 bp palindrome sequence.

<p>Cartoon depicts a portion of the palindrome sequence (chrX:139,502,939–139,502,970) with the positive strand folded upon itself in a hairpin loop (black). The four non-palindromic bases in the middle of the 180 bp sequence (TATC, bolded black) are predicted to form the head of the hairpin loop. The locations of the breakpoints on chromosome Xq27.1 for CMTX3 (orange); hypertrichosis¹ (red, [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1006177#pgen.1006177.ref037" target="_blank">37</a>]); hypertrichosis² (blue, [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1006177#pgen.1006177.ref037" target="_blank">37</a>]); hypertrichosis³ (green,[<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1006177#pgen.1006177.ref038" target="_blank">38</a>]); ptosis (pink; Bunyan [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1006177#pgen.1006177.ref039" target="_blank">39</a>]); and XX sex reversal (purple, Haines [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1006177#pgen.1006177.ref040" target="_blank">40</a>]) are marked out on the hairpin structure. Single breakpoints are depicted by a solid line. Multiple breakpoints are indicated by broken lines.</p

Characterization of the CMTX3 insertion.

<p>Sequence analysis of the proximal (A) and distal (B) breakpoints. Reference sequence for chromosome X and chromosome 8 are indicated in blue and orange, respectively. The distal breakpoint includes additional sequence from chromosome 12 (in green) and small rearrangements of the chromosome X sequence including an inversion of 12 bp, and a base pair substitution and a base pair deletion. (C) The 78 kb 8q24.3 sequence (in orange) contains the partial 5’<i>ARHGAP39</i> transcript which has been inserted 330 kb downstream and 84 kb upstream of the genes <i>LOC389895</i> and <i>SOX3</i>, respectively (in blue). The direction of transcripts are indicated by the arrow. (D) Location of the 78kb 8q24.3 insertion sequence (in orange) relative to the whole of the 5.7 Mb CMTX3 locus (in blue).</p

Identification and confirmation of a 78 kb chromosome 8q24.3 insertion in patients with CMTX3.

<p>(A) Whole genome sequencing depth of coverage for affected (red) and normal (black) males across the 8q24.3 insertion and flanking sequence. (B) Depiction of wild type chromosome X (top) and mutant chromosome X (bottom). The location of primers and amplicon sizes for the multiplex PCR genotyping assay are shown. Dotted red lines represent insertion breakpoints. (C) Size fractionation of multiplex PCR genotyping assay for a subset of family members from CMT623. Individual genotypes are depicted above the gel lane. Expected band sizes for the various primer combinations are listed to the right. Unaffected hemizygous males and homozygous females generate a single 340 bp amplicon; affected hemizygous males generate 595 bp and 235 bp amplicons crossing the proximal and distal breakpoints, respectively; carrier females amplify all three amplicons.</p

Split-reads and discordant paired ends mapping to Xq27.1 and 8q24.3 in whole genome sequencing data from affected males.

<p>Split-reads and discordant paired ends mapping to Xq27.1 and 8q24.3 in whole genome sequencing data from affected males.</p