July 7, 2019  |  

Interchromosomal core duplicons drive both evolutionary instability and disease susceptibility of the Chromosome 8p23.1 region.

Authors: Mohajeri, Kiana and Cantsilieris, Stuart and Huddleston, John and Nelson, Bradley J and Coe, Bradley P and Campbell, Catarina D and Baker, Carl and Harshman, Lana and Munson, Katherine M and Kronenberg, Zev N and Kremitzki, Milinn and Raja, Archana and Catacchio, Claudia Rita and Graves, Tina A and Wilson, Richard K and Ventura, Mario and Eichler, Evan E

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.© 2016 Mohajeri et al.; Published by Cold Spring Harbor Laboratory Press.

Journal: Genome research
DOI: 10.1101/gr.211284.116
Year: 2016

Read publication

Talk with an expert

If you have a question, need to check the status of an order, or are interested in purchasing an instrument, we're here to help.