RT Journal
A1 Mohajeri, Kiana
A1 Cantsilieris, Stuart
A1 Huddleston, John
A1 Nelson, Bradley J.
A1 Coe, Bradley P.
A1 Campbell, Catarina D.
A1 Baker, Carl
A1 Harshman, Lana
A1 Munson, Katherine M.
A1 Kronenberg, Zev N.
A1 Kremitzki, Milinn
A1 Raja, Archana
A1 Catacchio, Claudia Rita
A1 Graves, Tina A.
A1 Wilson, Richard K.
A1 Ventura, Mario
A1 Eichler, Evan E.
T1 Interchromosomal core duplicons drive both evolutionary instability and disease susceptibility of the Chromosome 8p23.1 region
JF Genome Research 
JO Genome Research 
YR 2016 
FD November 01 
VO 26 
IS 11 
SP 1453 
OP 1467 
DO 10.1101/gr.211284.116 
UL http://genome.cshlp.org/content/26/11/1453.abstract 
AB Recurrent rearrangements of Chromosome 8p23.1 are associated with congenital heart defects and developmental delay. The complexity of this region has led to inconsistencies in the current reference assembly, confounding studies of genetic variation. Using comparative sequence-based approaches, we generated a high-quality 6.3-Mbp alternate reference assembly of an inverted Chromosome 8p23.1 haplotype. Comparison with nonhuman primates reveals a 746-kbp duplicative transposition and two separate inversion events that arose in the last million years of human evolution. The breakpoints associated with these rearrangements map to an ape-specific interchromosomal core duplicon that clusters at sites of evolutionary inversion (P = 7.8 × 10−5). Refinement of microdeletion breakpoints identifies a subgroup of patients that map to the same interchromosomal core involved in the evolutionary formation of the duplication blocks. Our results define a higher-order genomic instability element that has shaped the structure of specific chromosomes during primate evolution contributing to rearrangements associated with inversion and disease.