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Evaluation of PRDM9 variation as a risk factor for recurrent genomic disorders and chromosomal non-disjunction

Evaluation of PRDM9 variation as a risk factor for recurrent genomic disorders and chromosomal non-disjunction
Evaluation of PRDM9 variation as a risk factor for recurrent genomic disorders and chromosomal non-disjunction
Recent studies have identified PRDM9, a zinc finger (ZF) protein, as a key regulator of meiotic recombination. As both recurrent genomic disorders and chromosomal non-disjunction are known to be associated with specific unusual patterns of recombination, we hypothesized a possible link between PRDM9 ZF variation and susceptibility to microdeletion syndromes and/or trisomy. We sequenced the PRDM9 ZF domain in 271 parents of patients with de novo microdeletions of known parental origin (velocardiofacial syndrome, the 17q21.31 microdeletion syndrome, Prader-Willi/Angelman syndrome and Williams-Beuren syndrome), and in 61 parents of individuals with a supernumerary X chromosome. We compared PRDM9 ZF genotype frequencies between parents in whose germ line the de novo rearrangement occurred and their spouses. We observed a significantly increased frequency (p = 0.006) of PRDM9 variants in parents who transmitted de novo 7q11.23 deletions to their offspring. These data suggest that certain PRDM9 alleles may be associated with an increased susceptibility to recurrent 7q11.23 microdeletions that cause Williams-Beuren syndrome. However, as the majority of parents who transmitted a de novo microdeletion/supernumerary X chromosome to their offspring have the common AA genotype, we conclude that none of the rearrangements we have studied are dependent on specific non-A PRDM9 alleles.
0340-6717
1519-1524
Borel, Christelle
80156acc-b968-4779-92e2-69719b0e2352
Cheung, Fanny
a15884f1-4ecd-4293-864b-27b7e15e0cc7
Stewart, Helen
f0a57ec9-3e87-4331-bf44-e00f32c432dd
Koolen, David A.
86423d8c-3a41-4dea-a9d6-c5f1949d5d77
Phillips, Christopher
f6aeb956-83fc-4cf2-b0b1-234405f489fd
Thomas, N. Simon
1a601957-288d-4f12-a9f7-4f4279b7f9b3
Jacobs, Patricia A.
d87ec15b-13c3-4868-96f1-b4b99030fa5b
Eliez, Stephan
94d3809e-76fc-4284-86f0-c07420741e92
Sharp, Andrew J.
4f814cb9-0069-4850-ad81-5ad57435f414
Borel, Christelle
80156acc-b968-4779-92e2-69719b0e2352
Cheung, Fanny
a15884f1-4ecd-4293-864b-27b7e15e0cc7
Stewart, Helen
f0a57ec9-3e87-4331-bf44-e00f32c432dd
Koolen, David A.
86423d8c-3a41-4dea-a9d6-c5f1949d5d77
Phillips, Christopher
f6aeb956-83fc-4cf2-b0b1-234405f489fd
Thomas, N. Simon
1a601957-288d-4f12-a9f7-4f4279b7f9b3
Jacobs, Patricia A.
d87ec15b-13c3-4868-96f1-b4b99030fa5b
Eliez, Stephan
94d3809e-76fc-4284-86f0-c07420741e92
Sharp, Andrew J.
4f814cb9-0069-4850-ad81-5ad57435f414

Borel, Christelle, Cheung, Fanny, Stewart, Helen, Koolen, David A., Phillips, Christopher, Thomas, N. Simon, Jacobs, Patricia A., Eliez, Stephan and Sharp, Andrew J. (2012) Evaluation of PRDM9 variation as a risk factor for recurrent genomic disorders and chromosomal non-disjunction. Human Genetics, 131 (9), 1519-1524. (PMID:22643917)

Record type: Article

Abstract

Recent studies have identified PRDM9, a zinc finger (ZF) protein, as a key regulator of meiotic recombination. As both recurrent genomic disorders and chromosomal non-disjunction are known to be associated with specific unusual patterns of recombination, we hypothesized a possible link between PRDM9 ZF variation and susceptibility to microdeletion syndromes and/or trisomy. We sequenced the PRDM9 ZF domain in 271 parents of patients with de novo microdeletions of known parental origin (velocardiofacial syndrome, the 17q21.31 microdeletion syndrome, Prader-Willi/Angelman syndrome and Williams-Beuren syndrome), and in 61 parents of individuals with a supernumerary X chromosome. We compared PRDM9 ZF genotype frequencies between parents in whose germ line the de novo rearrangement occurred and their spouses. We observed a significantly increased frequency (p = 0.006) of PRDM9 variants in parents who transmitted de novo 7q11.23 deletions to their offspring. These data suggest that certain PRDM9 alleles may be associated with an increased susceptibility to recurrent 7q11.23 microdeletions that cause Williams-Beuren syndrome. However, as the majority of parents who transmitted a de novo microdeletion/supernumerary X chromosome to their offspring have the common AA genotype, we conclude that none of the rearrangements we have studied are dependent on specific non-A PRDM9 alleles.

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More information

Accepted/In Press date: 30 May 2012
Published date: September 2012
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 339846
URI: https://eprints.soton.ac.uk/id/eprint/339846
ISSN: 0340-6717
PURE UUID: f75b3bc7-39cf-4a71-817a-db51f8980fb5

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Date deposited: 31 May 2012 12:47
Last modified: 18 Jul 2017 05:51

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Contributors

Author: Christelle Borel
Author: Fanny Cheung
Author: Helen Stewart
Author: David A. Koolen
Author: Christopher Phillips
Author: N. Simon Thomas
Author: Patricia A. Jacobs
Author: Stephan Eliez
Author: Andrew J. Sharp

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