A Fine-Scale Map of Recombination Rates and Hotspots Across the Human Genome

Genetic maps, which document the way in which recombination rates vary over a genome, are an essential tool for many genetic analyses. We present a high-resolution genetic map of the human genome, based on statistical analyses of genetic variation data, and identify more than 25,000 recombination hotspots, together with motifs and sequence contexts that play a role in hotspot activity. Differences between the behavior of recombination rates over large (megabase) and small (kilobase) scales lead us to suggest a two-stage model for recombination in which hotspots are stochastic features, within a framework in which large-scale rates are constrained.

[1]  J. Stamberg Genetic control of recombination in Schizophyllum commune: the occurrence and significance of natural variation , 1969, Heredity.

[2]  R. Hudson,et al.  Statistical properties of the number of recombination events in the history of a sample of DNA sequences. , 1985, Genetics.

[3]  B. Charlesworth,et al.  A test for the role of natural selection in the stabilization of transposable element copy number in a population of Drosophila melanogaster. , 1987, Genetical research.

[4]  R. Hudson,et al.  On the role of unequal exchange in the containment of transposable element copy number. , 1988, Genetical research.

[5]  M. Lichten,et al.  Factors that affect the location and frequency of meiosis-induced double-strand breaks in Saccharomyces cerevisiae. , 1995, Genetics.

[6]  N. Kleckner,et al.  Sequence non‐specific double‐strand breaks and interhomolog interactions prior to double‐strand break formation at a meiotic recombination hot spot in yeast. , 1995, The EMBO journal.

[7]  T. Petes,et al.  Meiosis-specific double-strand DNA breaks at the HIS4 recombination hot spot in the yeast Saccharomyces cerevisiae: control in cis and trans , 1995, Molecular and cellular biology.

[8]  T. Petes,et al.  Competition between adjacent meiotic recombination hotspots in the yeast Saccharomyces cerevisiae. , 1997, Genetics.

[9]  J C Murray,et al.  Pediatrics and , 1998 .

[10]  T. Petes,et al.  Meiotic recombination hot spots and cold spots , 2001, Nature Reviews Genetics.

[11]  P. Deloukas,et al.  Comparison of human genetic and sequence-based physical maps , 2001, Nature.

[12]  J. V. Moran,et al.  Initial sequencing and analysis of the human genome. , 2001, Nature.

[13]  A. Jeffreys,et al.  Reciprocal crossover asymmetry and meiotic drive in a human recombination hot spot , 2002, Nature Genetics.

[14]  D. Gudbjartsson,et al.  A high-resolution recombination map of the human genome , 2002, Nature Genetics.

[15]  M. Carrington,et al.  High-resolution patterns of meiotic recombination across the human major histocompatibility complex. , 2002, American journal of human genetics.

[16]  J. Wall,et al.  Comparative linkage-disequilibrium analysis of the beta-globin hotspot in primates. , 2003, American journal of human genetics.

[17]  J. Bonfield,et al.  Finishing the euchromatic sequence of the human genome , 2004, Nature.

[18]  Dana C Crawford,et al.  Evidence for substantial fine-scale variation in recombination rates across the human genome , 2004, Nature Genetics.

[19]  P. Donnelly,et al.  The Fine-Scale Structure of Recombination Rate Variation in the Human Genome , 2004, Science.

[20]  David Haussler,et al.  Comparative recombination rates in the rat, mouse, and human genomes. , 2004, Genome research.

[21]  Matthew Stephens,et al.  Absence of the TAP2 Human Recombination Hotspot in Chimpanzees , 2004, PLoS biology.

[22]  Nick Gilbert,et al.  Chromatin Architecture of the Human Genome Gene-Rich Domains Are Enriched in Open Chromatin Fibers , 2004, Cell.

[23]  P. Donnelly,et al.  Comparison of Fine-Scale Recombination Rates in Humans and Chimpanzees , 2005, Science.

[24]  Molly Przeworski,et al.  Fine-scale recombination patterns differ between chimpanzees and humans , 2005, Nature Genetics.

[25]  Geoffrey B. Nilsen,et al.  Whole-Genome Patterns of Common DNA Variation in Three Human Populations , 2005, Science.

[26]  Peter Donnelly,et al.  Human recombination hot spots hidden in regions of strong marker association , 2005, Nature Genetics.

[27]  A. Jeffreys,et al.  Factors influencing recombination frequency and distribution in a human meiotic crossover hotspot. , 2005, Human molecular genetics.

[28]  J. Jurka,et al.  Repbase Update, a database of eukaryotic repetitive elements , 2005, Cytogenetic and Genome Research.