Inter- and Intrachromosomal Rearrangements Are Both Involved in the Origin of 15q11-q13 Deletions in Prader-Willi Syndrome

Carrozzo, Romeo; Rossi, Elena; Christian, Susan L.; Kittikamron, Kirk; Livieri, C.; Corrias, Andrea; Pucci, Lucia; Fois, Alberto; Bosio, L.; Simi, Paolo; Beccaria, Luciano; Zuffardi, Orsetta; Ledbetter, David H.

doi:10.1086/513907

Cited by 66 publications

(46 citation statements)

References 16 publications

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“…Combining the results of these three studies with a fourth smaller one 26 gave 39 cases of grandmaternal origin compared to Taking all 21 deletions of 15q11 -q13, irrespective of parental origin, there was an overall excess of interchromosomal rearrangements. Combining our data with two published studies 28,29 there were 23 interchromosomal rearrangements (62%) and 14 intrachromosomal rearrangements (38%). For maternal deletions, haplotype analysis was performed using grandparents in nine cases and a sibling in five cases.…”

Section: Deletions Of Chromosome 22q11 (Digeorge Syndrome)supporting

confidence: 80%

“…These results extend the findings of Robinson et al 8 who reported that three out of three maternal cases and only two out of six paternal cases were interchromosomal. In contrast, Carrozzo et al 28 reported, an excess of interchromosomal cases among paternal deletions. Combining all these data together there are 14 maternal interchromosomal cases compared to three maternal intrachromosomal cases.…”

Section: Deletions Of Chromosome 22q11 (Digeorge Syndrome)mentioning

confidence: 86%

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

et al. 2006

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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.

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Section: Deletions Of Chromosome 22q11 (Digeorge Syndrome)supporting

confidence: 80%

Section: Deletions Of Chromosome 22q11 (Digeorge Syndrome)mentioning

confidence: 86%

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

et al. 2006

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“…The vast majority (>95%) of the deletion patients have clustered deletion breakpoint regions, with a single distal breakpoint and two proximal breakpoint regions (Christian et al 1995;Amos-Landgraf et al 1999). There is no apparent mechanistic differences for paternal and maternal deletions, as both inter-and intra-chromosomal rearrangements are seen in PWS and AS patients (Carrozzo et al 1997;Robinson et al 1998).…”

Section: End Repeats and Chromosome 15q11-15q13 Deletionsmentioning

confidence: 99%

Structure of Chromosomal Duplicons and their Role in Mediating Human Genomic Disorders

Ji¹,

Eichler²,

Schwartz³

et al. 2000

Genome Res.

231

158

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Chromosome-specific low-copy repeats, or duplicons, occur in multiple regions of the human genome. Homologous recombination between different duplicon copies leads to chromosomal rearrangements, such as deletions, duplications, inversions, and inverted duplications, depending on the orientation of the recombining duplicons. When such rearrangements cause dosage imbalance of a developmentally important gene(s), genetic diseases now termed genomic disorders result, at a frequency of 0.7–1/1000 births. Duplicons can have simple or very complex structures, with variation in copy number from 2 to >10 repeats, and each varying in size from a few kilobases in length to hundreds of kilobases. Analysis of the different duplicons involved in human genomic disorders identifies features that may predispose to recombination, including large size and high sequence identity between the recombining copies, putative recombination promoting features, and the presence of multiple genes/pseudogenes that may include genes expressed in germ cells. Most of the chromosome rearrangements involve duplicons near pericentromeric regions, which may relate to the propensity of such regions to accumulate duplicons. Detailed analyses of the structure, polymorphic variation, and mechanisms of recombination in genomic disorders, as well as the evolutionary origin of various duplicons will further our understanding of the structure, function, and fluidity of the human genome.

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“…For example, duplication of the 15q11-q14 interval is responsible for the most common form of marker chromosome formation among humans, accounting for >50% of all observed bisatellited supernumerary chromosomes . A 4-Mb microdeletion of the 15q11-13 region accounts for ∼70%-75% of all patients with Prader-Willi/Angelman syndrome (Mutirangura et al 1993;Carrozzo et al 1997). In addition to supernumerary marker chromosomes (SMCs) and microdeletions of the Prader-Willi/ Angelman critical region (PWACR) proximal 15q, several sporadic and inherited cases of interstitial duplications and triplications of the 15q11-13 region have been reported (Browne et al 1997).…”

Section: Pericentromeric Regions Are Prone To Genetic Instabilitymentioning

confidence: 99%

Masquerading Repeats: Paralogous Pitfalls of the Human Genome

Eichler¹

1998

Genome Res.

133

103

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Inter- and Intrachromosomal Rearrangements Are Both Involved in the Origin of 15q11-q13 Deletions in Prader-Willi Syndrome

Cited by 66 publications

References 16 publications

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

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

Structure of Chromosomal Duplicons and their Role in Mediating Human Genomic Disorders

Masquerading Repeats: Paralogous Pitfalls of the Human Genome

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