title: Parental and chromosomal origins of microdeletion and duplication syndromes involving 7q11.23, 15q11-q13 and 22q11.
abstract: Non-allelic homologous recombination between chromosome-specific LCRs is the most common mechanism leading to recurrent microdeletions and duplications. To look for locus-specific differences, we have used microsatellites to determine the parental and chromosomal origins of a large series of patients with de novo deletions of chromosome 7q11.23 (Williams syndrome), 15q11-q13 (Angelman syndrome, Prader-Willi syndrome) and 22q11 (Di George syndrome) and duplications of 15q11-q13. Overall the majority of rearrangements were interchromosomal, so arising from unequal meiotic exchange, and there were approximately equal numbers of maternal and paternal deletions. Duplications and deletions of 15q11-q13 appear to be reciprocal products that arise by the same mechanisms. The proportion arising from interchromosomal exchanges varied among deletions with 22q11 the highest and 15q11-q13 the lowest. However, parental and chromosomal origins were not always independent. For 15q11-q13, maternal deletions tended to be interchromosomal while paternal deletions tended to be intrachromosomal; for 22q11 there was a possible excess of maternal cases among intrachromosomal deletions. Several factors are likely to be involved in the formation of recurrent rearrangements and the relative importance of these appear to be locus-specific.
authors.affiliation: Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, UK. simon.thomas@salisbury.nhs.uk
authors.forename: N Simon
authors.initials: NS
authors.lastname: Thomas
authors.forename: Miranda
authors.initials: M
authors.lastname: Durkie
authors.forename: Gemma
authors.initials: G
authors.lastname: Potts
authors.forename: Richard
authors.initials: R
authors.lastname: Sandford
authors.forename: Berendine
authors.initials: B
authors.lastname: Van Zyl
authors.forename: Sheila
authors.initials: S
authors.lastname: Youings
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Dennis
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Jacobs
mesh_terms: D017204:Angelman Syndrome / Q000235:genetics*; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D004062:DiGeorge Syndrome / Q000235:genetics*; D005260:Female; D020440:Gene Duplication; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D018895:Microsatellite Repeats; D011218:Prader-Willi Syndrome / Q000235:genetics*; D011995:Recombination, Genetic; D018980:Williams Syndrome / Q000235:genetics*