title: Extended runs of homozygosity at 17q11.2: an association with type-2 NF1 deletions?
abstract: Large deletions in the NF1 gene region at 17q11.2 are caused by nonallelic homologous recombination (NAHR). The recurrent type-2 NF1 deletions span 1.2 Mb, with breakpoints in the SUZ12 gene and SUZ12P. Type-2 NF1 deletions occur preferentially during mitosis and are associated with somatic mosaicism. A panel of 16 type-2 NF1 deletions was used as a model system in which to investigate whether extended homozygosity across 17q11.2 might be associated with somatic deletion. Using SNP arrays, a 3.2 Mb interval encompassing the NF1 deletion region was found to harbor runs of homozygosity (ROHs) in different human populations. However, ROHs >or=500 kb directly flanking the NF1 deletion region on both sides were not found to occur disproportionately in NF1 patients harboring type-2 deletions compared to controls. Although low allelic diversity in 17q11.2 is unlikely to be a key factor in promoting NAHR-mediated somatic type-2 deletions, a specific ROH of 588 kb (roh1), located some 525 kb proximal to the deletion interval, was found to occur more frequently (P=0.012) in the type-2 deletion patients compared with controls. We postulate that roh1 may act remotely, via an as yet unknown mechanism, to increase the frequency of somatic recombination between the distally duplicated SUZ12 sequences.
authors.affiliation: Institute of Human Genetics, University of Ulm, Ulm, Germany.
authors.forename: Angelika C
authors.initials: AC
authors.lastname: Roehl
authors.forename: David N
authors.initials: DN
authors.lastname: Cooper
authors.forename: Lan
authors.initials: L
authors.lastname: Kluwe
authors.forename: Andreas
authors.initials: A
authors.lastname: Helbrich
authors.forename: Katharina
authors.initials: K
authors.lastname: Wimmer
authors.forename: Josef
authors.initials: J
authors.lastname: Högel
authors.forename: Victor-Felix
authors.initials: VF
authors.lastname: Mautner
authors.forename: Hildegard
authors.initials: H
authors.lastname: Kehrer-Sawatzki
mesh_terms: D000483:Alleles; D002875:Chromosomes / Q000648:ultrastructure; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D017353:Gene Deletion; D016514:Genes, Neurofibromatosis 1; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008938:Mitosis; D008957:Models, Genetic; D009154:Mutation; D009456:Neurofibromatosis 1 / Q000235:genetics*; D025542:Neurofibromin 1 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011995:Recombination, Genetic
chemical_list: D025542:Neurofibromin 1