title: Interlocus gene conversion explains at least 2.7% of single nucleotide variants in human segmental duplications.
abstract: BACKGROUND
  Interlocus gene conversion (IGC) is a recombination-based mechanism that results in the unidirectional transfer of short stretches of sequence between paralogous loci. Although IGC is a well-established mechanism of human disease, the extent to which this mutagenic process has shaped overall patterns of segregating variation in multi-copy regions of the human genome remains unknown. One expected manifestation of IGC in population genomic data is the presence of one-to-one paralogous SNPs that segregate identical alleles.
  
  
  RESULTS
  Here, I use SNP genotype calls from the low-coverage phase 3 release of the 1000 Genomes Project to identify 15,790 parallel, shared SNPs in duplicated regions of the human genome. My approach for identifying these sites accounts for the potential redundancy of short read mapping in multi-copy genomic regions, thereby effectively eliminating false positive SNP calls arising from paralogous sequence variation. I demonstrate that independent mutation events to identical nucleotides at paralogous sites are not a significant source of shared polymorphisms in the human genome, consistent with the interpretation that these sites are the outcome of historical IGC events. These putative signals of IGC are enriched in genomic contexts previously associated with non-allelic homologous recombination, including clear signals in gene families that form tandem intra-chromosomal clusters.
  
  
  CONCLUSIONS
  Taken together, my analyses implicate IGC, not point mutation, as the mechanism generating at least 2.7% of single nucleotide variants in duplicated regions of the human genome.
authors.affiliation: Initiative in Biological Complexity, North Carolina State University, 112 Derieux Place, 3510 Thomas Hall, Campus Box 7614, Raleigh, NC, 27695-7614, USA. bldumont@ncsu.edu.
authors.forename: Beth L
authors.initials: BL
authors.lastname: Dumont
mesh_terms: D000483:Alleles; D005785:Gene Conversion / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics; D009711:Nucleotides / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D056916:Segmental Duplications, Genomic / Q000235:genetics*
chemical_list: D009711:Nucleotides