title: Correlation between frequency of non-allelic homologous recombination and homology properties: evidence from homology-mediated CNV mutations in the human genome.
abstract: Non-allelic homologous recombination (NAHR) is one of the key mechanisms of DNA rearrangement. NAHR occurring between direct homologous repeats can generate genomic copy number variation (CNV) and make significant contributions to both genome evolution and human diseases such as cancer. Intriguingly, previous observations on the rare CNVs at certain genomic disorder loci suggested that NAHR frequency could be dependent on homology properties. However, such a correlation remains unclear at the other NAHR-mediated CNV loci, especially the common CNVs in human populations. Different from the rare CNVs associated with genomic disorders, it is challenging to identify de novo NAHR events at common CNV loci. Therefore, our previously proposed statistic M was employed in estimating relative mutation rate for the NAHR-mediated CNVs in human populations. By utilizing generalized regression neural network and principal component analysis in studying 4330 CNVs ascertained in 3 HapMap populations, we identified the CNVs mediated by NAHR between paired segmental duplications (SDs) and further revealed the correlations between SD properties and NAHR probability. SD length and inter-SD distance were shown to make major contributions to the occurrence of NAHR, whereas chromosomal position and sequence similarity of paired SDs are also involved in NAHR. An integrated effect of SD properties on NAHR frequency was revealed for the common CNVs in human populations. These observations can be well explained by ectopic synapsis in NAHR together with our proposed model of chromosomal compression/extension/looping (CCEL) for homology mis-pairing. Our findings showed the important roles of SDs in NAHR and human genomic evolution.
authors.affiliation: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology and Department of Biology, Washington University in St. Louis, St. Louis, MO 63130, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology and.
authors.forename: Weichen
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology and.
authors.forename: Renqian
authors.initials: R
authors.lastname: Du
authors.affiliation: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200438, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200438, China, zhangfeng@fudan.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000483:Alleles; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism; D056915:DNA Copy Number Variations; D019143:Evolution, Molecular; D015321:Gene Rearrangement; D056426:Genetic Loci; D015894:Genome, Human; D023281:Genomics; D059765:Homologous Recombination; D006801:Humans; D008962:Models, Theoretical; D059645:Mutation Rate; D025341:Principal Component Analysis; D012091:Repetitive Sequences, Nucleic Acid; D056916:Segmental Duplications, Genomic; D016415:Sequence Alignment