title: The variant inv(2)(p11.2q13) is a genuinely recurrent rearrangement but displays some breakpoint heterogeneity.
abstract: Human chromosome 2 contains large blocks of segmental duplications (SDs), both within and between proximal 2p and proximal 2q, and these may contribute to the frequency of the common variant inversion inv(2)(p11.2q13). Despite their being cytogenetically homogeneous, we have identified four different breakpoint combinations by fluorescence in situ hybridization mapping of 40 cases of inv(2)(p11.2q13) of European origin. For the vast majority of inversions (35/40), the breakpoints fell within the same spanning BACs, which hybridized to both 2p11.2 and 2q13 on the normal and inverted homologues. Sequence analysis revealed that these BACs contain a significant proportion of intrachromosomal SDs with sequence homology to the reciprocal breakpoint region. In contrast, BACs spanning the rare breakpoint combinations contain fewer SDs and with sequence homology only to the same chromosome arm. Using haplotype analysis, we identified a number of related family subgroups with identical or very closely related haplotypes. However, the majority of cases were not related, demonstrating for the first time that the inv(2)(p11.2q13) is a truly recurrent rearrangement. Therefore, there are three explanations to account for the frequent observation of the inv(2)(p11.2q13): the majority have arisen independently in different ancestors, while a minority either have been transmitted from a common founder or have different breakpoints at the molecular cytogenetic level.
authors.affiliation: Institut fur Humangenetik und Anthropologie, Friedrich-Schiller University, Jena, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Fickelscher
authors.forename: Thomas
authors.initials: T
authors.lastname: Liehr
authors.forename: Kathryn
authors.initials: K
authors.lastname: Watts
authors.forename: Victoria
authors.initials: V
authors.lastname: Bryant
authors.forename: John C K
authors.initials: JC
authors.lastname: Barber
authors.forename: Simone
authors.initials: S
authors.lastname: Heidemann
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Jens Michael
authors.initials: JM
authors.lastname: Hertz
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Tumer
authors.forename: N
authors.initials: N
authors.lastname: Simon Thomas
mesh_terms: D019457:Chromosome Breakage; D007446:Chromosome Inversion; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D015321:Gene Rearrangement; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping