Francesca Antonacci, Jeffrey M. Kidd, Tomas Marques-Bonet, Brian O’Roak, Mario Ventura, Santhosh
Girirajan, Can Alkan, Laura Vives, Maika Malig, Jill A. Rosenberg, Lisa G. Shaffer, Tina A. Graves, Richard
K. Wilson, David G. Schwartz and Evan E Eichler. “A large, complex structural polymorphism at 16p12.1
underlies microdeletion disease risk” Nature Genetics, 2010 Sep;42(9):745-50. Epub 2010 Aug 22.
In this project, we identified what appeared to be one of the largest inconsistencies of the human
reference genome. Various genomic analyses (optical mapping, FISH, clone mapping and sequencing)
show that the current human genome assembly is inverted for the gene order of a 1.1 Mbp region on
16p12.1. Evolutionary reconstruction in non-human primates reveals that this complex architecture arose
from the integration of segmental duplications which expanded this region of euchromatin from 720 kbp
to 1.6 Mbp precipitating two local inversions within the human lineage over the last 10 million years (this
was my main contribution to this project). We found two major human haplotypes, and more importantly,
one of the configurations contains a particular duplicated sequence in direct orientation, predisposing this
configuration to non-allelic homologous recombination and disease associated microdeletion.