Polymorphic variation in human meiotic recombination.

In this study, our phenotype of interest is meiotic recombination. Using genotypes of approximately 6,000 SNP markers in members of the Centre d'Etude du Polymorphisme Humain Utah pedigrees, we found extensive individual variation in the number of female and male recombination events. The locations and frequencies of these recombination events vary along the genome. In both female and male meiosis, the regions with the most recombination events are found at the ends of the chromosomes. Our analysis also shows that there are polymorphic differences among individuals in the activity of the recombination "jungles"; these preferred sites of meiotic recombination differ greatly among individuals. These findings have important implications for understanding genetic disorders that result from improper chromosome segregation.

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

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

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

[4]  J. Hegemann,et al.  Cis-acting determinants affecting centromere function, sister-chromatid cohesion and reciprocal recombination during meiosis in Saccharomyces cerevisiae. , 1995, Genetics.

[5]  A. Jeffreys,et al.  Intensely punctate meiotic recombination in the class II region of the major histocompatibility complex , 2001, Nature Genetics.

[6]  T. Hassold,et al.  Effect of meiotic recombination on the production of aneuploid gametes in humans , 2005, Cytogenetic and Genome Research.

[7]  S. Schwartz,et al.  Covariation of Synaptonemal Complex Length and Mammalian Meiotic Exchange Rates , 2002, Science.

[8]  L. Lazzeroni,et al.  Individual variation in recombination among human males. , 1996, American journal of human genetics.

[9]  K. Lange,et al.  Single-sperm typing: determination of genetic distance between the G gamma-globin and parathyroid hormone loci by using the polymerase chain reaction and allele-specific oligomers. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[10]  D. Gudbjartsson,et al.  Recombination rate and reproductive success in humans , 2004, Nature Genetics.

[11]  G. D. Stewart,et al.  A genetic linkage map of human chromosome 21: analysis of recombination as a function of sex and age. , 1992, American journal of human genetics.

[12]  M. Steinmetz,et al.  Gene organization and recombinational hotspots in the murine major histocompatibility complex , 1986, Cell.

[13]  R. Hawley,et al.  Spontaneous X chromosome MI and MII nondisjunction events in Drosophila melanogaster oocytes have different recombinational histories , 1996, Nature Genetics.

[14]  A. Jeffreys,et al.  High-resolution mapping of crossovers in human sperm defines a minisatellite-associated recombination hotspot. , 1998, Molecular cell.

[15]  A. Jeffreys,et al.  Polymorphism in the activity of human crossover hotspots independent of local DNA sequence variation. , 2006, Human molecular genetics.

[16]  T. Hassold,et al.  Variation in human meiotic recombination. , 2004, Annual review of genomics and human genetics.

[17]  Geraldine M Hartshorne,et al.  Patterns of meiotic recombination in human fetal oocytes. , 2002, American journal of human genetics.

[18]  H. Cann,et al.  Centre d'etude du polymorphisme humain (CEPH): collaborative genetic mapping of the human genome. , 1990, Genomics.

[19]  T. Prolla,et al.  Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over , 1996, Nature Genetics.

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

[21]  A. Jeffreys,et al.  High resolution analysis of haplotype diversity and meiotic crossover in the human TAP2 recombination hotspot. , 2000, Human molecular genetics.

[22]  B. Paigen,et al.  A Torrid Zone on Mouse Chromosome 1 Containing a Cluster of Recombinational Hotspots , 2005, Genetics.

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

[24]  A. Rademaker,et al.  Variation in MLH1 distribution in recombination maps for individual chromosomes from human males. , 2006, Human molecular genetics.

[25]  Jeremy Heil,et al.  A 3.9-centimorgan-resolution human single-nucleotide polymorphism linkage map and screening set. , 2003, American journal of human genetics.