Characterisation of interstitial duplications and triplications of chromosome 15q11–q13

Abstract

Chromosome 15 is frequently involved in the formation of structural rearrangements. We report the molecular characterisation of 16 independent interstitial duplications, including those of one individual who carried a duplication on both of her chromosomes 15, and three interstitial triplications of the Prader-Willi/Angelman syndrome critical region (PWACR). In all probands except one, the rearrangement was maternal in origin. In one family, the duplication was paternal in origin, yet appeared to segregate in a sibship of three with an abnormal phenotype that included developmental delay and a behavioural disorder. Ten duplications were familial, five de novo and one unknown. All 16 duplications, including two not visible by routine G-banding, were of an almost uniform size and shared the common deletion breakpoints of Prader-Willi syndrome and Angelman syndrome. Like deletions, the formation of duplications can occur in both male and female meiosis and involve both inter- and intrachromosomal events. This implies that at least some deletions and duplications are the reciprocal products of each other. We observed no instances of meiotic instability in the transmission of a duplication, although recombination within the PWACR occurred in two members of the same family between the normal and the duplicated chromosome 15 homologues. All three triplications arose de novo and included alleles from both maternal chromosomes 15. Triplication breakpoints were more variable and extended distally beyond the PWACR. The molecular characteristics of duplications and triplications suggest that they are formed by different mechanisms.

Parental and chromosomal origins of microdeletion and duplication syndromes involving 7q11.23, 15q11-q13 and 22q11

“…Seven of the de novo duplications studied had arisen maternally and two paternally (Table 3, family numbers 6, 7, 8, 11, 14, 15 have been reported previously 31 ).…”

Low-copy repeats at the human VIPR2 gene predispose to recurrent and nonrecurrent rearrangements

“…Alternatively, the triplications could form by U-type exchanges between three chromatids. [26][27][28][29] One exchange between homologous chromatids would take place at the distal breakpoint region, the other at the proximal breakpoint region, between either sister chromatids or homologous chromosomes. Brewer et al 23 proposed a replicationbased mechanism, supported by yeast observations, involving the generation of a dimeric inverted circular intermediate.…”

Recurrent rearrangements in the proximal 15q11–q14 region: a new breakpoint cluster specific to unbalanced translocations

“…It was initially located between markers D15S12 and D15S24 ( 33 , for review) and has been subsequently more precisely located between markers D15S931 and D15S1019. 12,20,31 Two other distal BPs, BP4 and BP5, which have not been fully characterized, are involved in cases of large 15q11 -q14 interstitial triplications and inv dup (15) chromosomes. BP4 has been mapped between markers D15S1019 and D15S165 and BP5 between markers D15S165 and D15S144.…”