DNA recombination. Recombination initiation maps of individual human genomes.
DNA double-strand breaks (DSBs) are introduced in meiosis to initiate recombination and generate crossovers, the reciprocal exchanges of genetic material between parental chromosomes. Here, we present high-resolution maps of meiotic DSBs in individual human genomes. Comparing DSB maps between individuals shows that along with DNA binding by PRDM9, additional factors may dictate the efficiency of DSB formation. We find evidence for both GC-biased gene conversion and mutagenesis around meiotic DSB hotspots, while frequent colocalization of DSB hotspots with chromosome rearrangement breakpoints implicates the aberrant repair of meiotic DSBs in genomic disorders. Furthermore, our data indicate that DSB frequency is a major determinant of crossover rate. These maps provide new insights into the regulation of meiotic recombination and the impact of meiotic recombination on genome function.
National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, MD, USA.
Florencia
F
Pratto
National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, MD, USA.
Kevin
K
Brick
National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, MD, USA.
Pavel
P
Khil
Department of Biochemistry and Molecular Biology, Uniformed Services University of Health Sciences, Bethesda, MD, USA.
Fatima
F
Smagulova
Department of Biochemistry and Molecular Biology, Uniformed Services University of Health Sciences, Bethesda, MD, USA. rdcamerini@mail.nih.gov galina.petukhova@usuhs.edu.
Galina V
GV
Petukhova
National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, MD, USA. rdcamerini@mail.nih.gov galina.petukhova@usuhs.edu.
R Daniel
RD
Camerini-Otero
D000483:Alleles; D002874:Chromosome Mapping; D053903:DNA Breaks, Double-Stranded; D015894:Genome, Human / Q000235:genetics*; D042822:Genomic Instability; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D059765:Homologous Recombination; D006801:Humans; D008297:Male; D008540:Meiosis / Q000235:genetics*; D011485:Protein Binding; D013090:Spermatocytes; D016615:Telomere / Q000235:genetics
D011495:Histone-Lysine N-Methyltransferase; C544431:PRDM9 protein, human