RT Journal
A1 Hussin, Julie
A1 Sinnett, Daniel
A1 Casals, Ferran
A1 Idaghdour, Youssef
A1 Bruat, Vanessa
A1 Saillour, Virginie
A1 Healy, Jasmine
A1 Grenier, Jean-Christophe
A1 De Malliard, Thibault
A1 Spinella, Jean-Francois
A1 Lariviere, Mathieu
A1 Busche, Stephan
A1 Gibson, Greg
A1 Andersson, Anna
A1 Holmfeldt, Linda
A1 Ma, Jing
A1 Wei, Lei
A1 Zhang, Jinghui
A1 Andelfinger, Gregor
A1 Downing, James
A1 Mullighan, Charles
A1 Awadalla, Phillip
T1 Rare allelic forms of PRDM9 associated with childhood leukemogenesis
JF Genome Research 
JO Genome Research 
YR 2012 
FD December 05 
DO 10.1101/gr.144188.112 
SP gr.144188.112 
UL http://genome.cshlp.org/content/early/2012/12/05/gr.144188.112.abstract 
AB One of the most rapidly evolving genes in humans, PRDM9, is a key determinant of the distribution of meiotic recombination events. Mutations in this meiotic-specific gene have previously been associated with male infertility in humans and recent studies suggest that PRDM9 may be involved in pathological genomic rearrangements. By studying genomes from families with children affected by B-cell precursor acute lymphoblastic leukemia (B-ALL), we characterized meiotic recombination patterns within a family with two siblings having hyperdiploid childhood ALL and observed unusual localization of maternal recombination events. The mother of the family carries a rare PRDM9 allele, potentially explaining the unusual patterns found. From exomes sequenced in 44 additional parents of children affected with B-ALL, we discovered a substantial and significant excess of rare allelic forms of PRDM9. The rare PRDM9 alleles are transmitted to the affected children in half the cases, nonetheless there remains a significant excess of rare alleles among patients relative to controls. We successfully replicated this latter observation in an independent cohort of 50 children with B-ALL, where we found an excess of rare PRDM9 alleles in aneuploid and infant B-ALL patients. PRDM9 variability in humans is thought to influence genomic instability, and these data support a potential role for PRDM9 variation in risk of acquiring aneuploidies or genomic rearrangements associated with childhood leukemogenesis.