A common sequence motif associated with recombination hot spots and genome instability in humans

Simon Myers; Colin Freeman; Adam Auton; Peter Donnelly; Gil McVean

doi:10.1038/ng.213

A common sequence motif associated with recombination hot spots and genome instability in humans

Simon Myers, Colin Freeman, Adam Auton, Peter Donnelly, Gil McVean

Research output: Contribution to journal › Article › peer-review

347 Scopus citations

Abstract

In humans, most meiotic crossover events are clustered into short regions of the genome known as recombination hot spots. We have previously identified DNA motifs that are enriched in hot spots, particularly the 7-mer CCTCCCT. Here we use the increased hot-spot resolution afforded by the Phase 2 HapMap and novel search methods to identify an extended family of motifs based around the degenerate 13-mer CCNCCNTNNCCNC, which is critical in recruiting crossover events to at least 40% of all human hot spots and which operates on diverse genetic backgrounds in both sexes. Furthermore, these motifs are found in hypervariable minisatellites and are clustered in the breakpoint regions of both disease-causing nonallelic homologous recombination hot spots and common mitochondrial deletion hot spots, implicating the motif as a driver of genome instability.

Original language	English (US)
Pages (from-to)	1124-1129
Number of pages	6
Journal	Nature Genetics
Volume	40
Issue number	9
DOIs	https://doi.org/10.1038/ng.213
State	Published - Sep 2008
Externally published	Yes

ASJC Scopus subject areas

Genetics

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ng.213

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title = "A common sequence motif associated with recombination hot spots and genome instability in humans",

abstract = "In humans, most meiotic crossover events are clustered into short regions of the genome known as recombination hot spots. We have previously identified DNA motifs that are enriched in hot spots, particularly the 7-mer CCTCCCT. Here we use the increased hot-spot resolution afforded by the Phase 2 HapMap and novel search methods to identify an extended family of motifs based around the degenerate 13-mer CCNCCNTNNCCNC, which is critical in recruiting crossover events to at least 40% of all human hot spots and which operates on diverse genetic backgrounds in both sexes. Furthermore, these motifs are found in hypervariable minisatellites and are clustered in the breakpoint regions of both disease-causing nonallelic homologous recombination hot spots and common mitochondrial deletion hot spots, implicating the motif as a driver of genome instability.",

author = "Simon Myers and Colin Freeman and Adam Auton and Peter Donnelly and Gil McVean",

note = "Funding Information: We thank J. Lupski for help with compiling information on NAHR hot spots and G. Coop for discussion. We thank the Engineering and Physical Sciences Research Council (EPSRC), the Wolfson Foundation, the EU and the Wellcome Trust for financial support.",

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AU - Myers, Simon

AU - Freeman, Colin

AU - Auton, Adam

AU - Donnelly, Peter

AU - McVean, Gil

N1 - Funding Information: We thank J. Lupski for help with compiling information on NAHR hot spots and G. Coop for discussion. We thank the Engineering and Physical Sciences Research Council (EPSRC), the Wolfson Foundation, the EU and the Wellcome Trust for financial support.

PY - 2008/9

Y1 - 2008/9

N2 - In humans, most meiotic crossover events are clustered into short regions of the genome known as recombination hot spots. We have previously identified DNA motifs that are enriched in hot spots, particularly the 7-mer CCTCCCT. Here we use the increased hot-spot resolution afforded by the Phase 2 HapMap and novel search methods to identify an extended family of motifs based around the degenerate 13-mer CCNCCNTNNCCNC, which is critical in recruiting crossover events to at least 40% of all human hot spots and which operates on diverse genetic backgrounds in both sexes. Furthermore, these motifs are found in hypervariable minisatellites and are clustered in the breakpoint regions of both disease-causing nonallelic homologous recombination hot spots and common mitochondrial deletion hot spots, implicating the motif as a driver of genome instability.

AB - In humans, most meiotic crossover events are clustered into short regions of the genome known as recombination hot spots. We have previously identified DNA motifs that are enriched in hot spots, particularly the 7-mer CCTCCCT. Here we use the increased hot-spot resolution afforded by the Phase 2 HapMap and novel search methods to identify an extended family of motifs based around the degenerate 13-mer CCNCCNTNNCCNC, which is critical in recruiting crossover events to at least 40% of all human hot spots and which operates on diverse genetic backgrounds in both sexes. Furthermore, these motifs are found in hypervariable minisatellites and are clustered in the breakpoint regions of both disease-causing nonallelic homologous recombination hot spots and common mitochondrial deletion hot spots, implicating the motif as a driver of genome instability.

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A common sequence motif associated with recombination hot spots and genome instability in humans

Abstract

ASJC Scopus subject areas

UN SDGs

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