Rare allelic forms of PRDM9 associated with childhood leukemogenesis

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Rare allelic forms of PRDM9 associated with childhood leukemogenesis. / Hussin, Julie; Sinnett, Daniel; Casals, Ferran; Idaghdour, Youssef; Bruat, Vanessa; Saillour, Virginie; Healy, Jasmine; Grenier, Jean-Christophe; de Malliard, Thibault; Busche, Stephan; Spinella, Jean-François; Larivière, Mathieu; Gibson, Greg; Andersson, Anna; Holmfeldt, Linda; Ma, Jing; Wei, Lei; Zhang, Jinghui; Andelfinger, Gregor; Downing, James R; Mullighan, Charles G; Awadalla, Philip.

In: Genome Research, Vol. 23, No. 3, 03.2013, p. 419-30.

Research output: Contribution to journalArticle

Harvard

Hussin, J, Sinnett, D, Casals, F, Idaghdour, Y, Bruat, V, Saillour, V, Healy, J, Grenier, J-C, de Malliard, T, Busche, S, Spinella, J-F, Larivière, M, Gibson, G, Andersson, A, Holmfeldt, L, Ma, J, Wei, L, Zhang, J, Andelfinger, G, Downing, JR, Mullighan, CG & Awadalla, P 2013, 'Rare allelic forms of PRDM9 associated with childhood leukemogenesis', Genome Research, vol. 23, no. 3, pp. 419-30. https://doi.org/10.1101/gr.144188.112

APA

Hussin, J., Sinnett, D., Casals, F., Idaghdour, Y., Bruat, V., Saillour, V., ... Awadalla, P. (2013). Rare allelic forms of PRDM9 associated with childhood leukemogenesis. Genome Research, 23(3), 419-30. https://doi.org/10.1101/gr.144188.112

CBE

Hussin J, Sinnett D, Casals F, Idaghdour Y, Bruat V, Saillour V, Healy J, Grenier J-C, de Malliard T, Busche S, Spinella J-F, Larivière M, Gibson G, Andersson A, Holmfeldt L, Ma J, Wei L, Zhang J, Andelfinger G, Downing JR, Mullighan CG, Awadalla P. 2013. Rare allelic forms of PRDM9 associated with childhood leukemogenesis. Genome Research. 23(3):419-30. https://doi.org/10.1101/gr.144188.112

MLA

Vancouver

Hussin J, Sinnett D, Casals F, Idaghdour Y, Bruat V, Saillour V et al. Rare allelic forms of PRDM9 associated with childhood leukemogenesis. Genome Research. 2013 Mar;23(3):419-30. https://doi.org/10.1101/gr.144188.112

Author

Hussin, Julie ; Sinnett, Daniel ; Casals, Ferran ; Idaghdour, Youssef ; Bruat, Vanessa ; Saillour, Virginie ; Healy, Jasmine ; Grenier, Jean-Christophe ; de Malliard, Thibault ; Busche, Stephan ; Spinella, Jean-François ; Larivière, Mathieu ; Gibson, Greg ; Andersson, Anna ; Holmfeldt, Linda ; Ma, Jing ; Wei, Lei ; Zhang, Jinghui ; Andelfinger, Gregor ; Downing, James R ; Mullighan, Charles G ; Awadalla, Philip. / Rare allelic forms of PRDM9 associated with childhood leukemogenesis. In: Genome Research. 2013 ; Vol. 23, No. 3. pp. 419-30.

RIS

TY - JOUR

T1 - Rare allelic forms of PRDM9 associated with childhood leukemogenesis

AU - Hussin, Julie

AU - Sinnett, Daniel

AU - Casals, Ferran

AU - Idaghdour, Youssef

AU - Bruat, Vanessa

AU - Saillour, Virginie

AU - Healy, Jasmine

AU - Grenier, Jean-Christophe

AU - de Malliard, Thibault

AU - Busche, Stephan

AU - Spinella, Jean-François

AU - Larivière, Mathieu

AU - Gibson, Greg

AU - Andersson, Anna

AU - Holmfeldt, Linda

AU - Ma, Jing

AU - Wei, Lei

AU - Zhang, Jinghui

AU - Andelfinger, Gregor

AU - Downing, James R

AU - Mullighan, Charles G

AU - Awadalla, Philip

PY - 2013/3

Y1 - 2013/3

N2 - 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. In 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 B-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.

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. In 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 B-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.

KW - Adolescent

KW - Alleles

KW - Child

KW - Child, Preschool

KW - Cohort Studies

KW - Crossing Over, Genetic

KW - Exome

KW - Female

KW - Gene Frequency

KW - Gene Rearrangement

KW - Genomic Instability

KW - Histone-Lysine N-Methyltransferase/genetics

KW - Humans

KW - Infant

KW - Leukemia, Biphenotypic, Acute/genetics

KW - Male

KW - Meiosis

KW - Microarray Analysis

KW - Mutation

KW - Pedigree

KW - Polymorphism, Single Nucleotide

KW - Recombination, Genetic

KW - Sequence Analysis, DNA

KW - Translocation, Genetic

U2 - 10.1101/gr.144188.112

DO - 10.1101/gr.144188.112

M3 - Article

VL - 23

SP - 419

EP - 430

JO - Genome Research

JF - Genome Research

SN - 1549-5469

IS - 3

ER -