title: A recombination hotspot responsible for two inherited peripheral neuropathies is located near a mariner transposon-like element.
abstract: The Charcot-Marie Tooth disease type 1A (CMT1A) duplication and hereditary neuropathy with liability to pressure palsies (HNPP) deletion are reciprocal products of an unequal crossing-over event between misaligned flanking CMT1A-REP repeats. The molecular aetiology of this apparently homologous recombination event was examined by sequencing the crossover region. Through the detection of novel junction fragments from the recombinant CMT1A-REPs in both CMT1A and HNPP patients, a 1.7-kb recombination hotspot within the approximately 30-kb CMT1A-REPs was identified. This hotspot is 98% identical between CMT1A-REPs indicating that sequence identity is not likely the sole factor involved in promoting crossover events. Sequence analysis revealed a mariner transposon-like element (MITE) near the hotspot which we hypothesize could mediate strand exchange events via cleavage by a transposase at or near the 3' end of the element.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA.
authors.forename: L T
authors.initials: LT
authors.lastname: Reiter
authors.forename: T
authors.initials: T
authors.lastname: Murakami
authors.forename: T
authors.initials: T
authors.lastname: Koeuth
authors.forename: L
authors.initials: L
authors.lastname: Pentao
authors.forename: D M
authors.initials: DM
authors.lastname: Muzny
authors.forename: R A
authors.initials: RA
authors.lastname: Gibbs
authors.forename: J R
authors.initials: JR
authors.lastname: Lupski
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D004247:DNA; D004251:DNA Transposable Elements; D017353:Gene Deletion; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D010523:Peripheral Nervous System Diseases / Q000235:genetics*; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid
chemical_list: D004251:DNA Transposable Elements; D004247:DNA