title: Population-specific differences in gene conversion patterns between human SUZ12 and SUZ12P are indicative of the dynamic nature of interparalog gene conversion.
abstract: Nonallelic homologous gene conversion (NAHGC) resulting from interparalog recombination without crossover represents an important influence on the evolution of duplicated sequences in the human genome. In 17q11.2, different paralogous sequences mediate large NF1 deletions by nonallelic homologous recombination with crossover (NAHR). Among these paralogs are SUZ12 and its pseudogene SUZ12P which harbour the breakpoints of type-2 (1.2-Mb) NF1 deletions. Such deletions are caused predominantly by mitotic NAHR since somatic mosaicism with normal cells is evident in most patients. Investigating whether SUZ12 and SUZ12P have also been involved in NAHGC, we observed gene conversion tracts between these paralogs in both Africans (AFR) and Europeans (EUR). Since germline type-2 NF1 deletions resulting from meiotic NAHR are very rare, the vast majority of the gene conversion tracts in SUZ12 and SUZ12P are likely to have resulted from mitotic recombination during premeiotic cell divisions of germ cells. A higher number of gene conversion tracts were noted within SUZ12 and SUZ12P in AFR as compared to EUR. Further, the distinctive signature of NAHGC (a high number of SNPs per paralog and a high number of shared SNPs between paralogs), a characteristic of many actively recombining paralogs, was observed in both SUZ12 and SUZ12P but only in AFR and not in EUR. A novel polymorphic 2.3-kb deletion in SUZ12P was identified which exhibited a high allele frequency in EUR. We postulate that this interparalog structural difference, together with low allelic recombination rates, could have caused a reduction in NAHGC between SUZ12 and SUZ12P during human evolution.
authors.affiliation: Institute of Human Genetics, University of Ulm, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Mussotter
authors.forename: Kathrin
authors.initials: K
authors.lastname: Bengesser
authors.forename: Josef
authors.initials: J
authors.lastname: Högel
authors.forename: David N
authors.initials: DN
authors.lastname: Cooper
authors.forename: Hildegard
authors.initials: H
authors.lastname: Kehrer-Sawatzki
mesh_terms: D000818:Animals; D005785:Gene Conversion; D005828:Genetics, Population; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D009363:Neoplasm Proteins; D002679:Pan troglodytes; D063151:Polycomb Repressive Complex 2 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors
chemical_list: D009363:Neoplasm Proteins; C430461:SUZ12 protein, human; D014157:Transcription Factors; D063151:Polycomb Repressive Complex 2