title: Identification of consensus motifs associated with mitotic recombination and clinical characteristics in patients with paternal uniparental isodisomy of chromosome 11.
abstract: Uniparental disomy (UPD) is defined as the inheritance of both homologs of a given genomic region from only one parent. The majority of UPD includes an entire chromosome. However, the extent of UPD is sometimes limited to a subchromosomal region (segmental UPD). Mosaic paternal UPD (pUPD) of chromosome 11 is found in approximately 20% of patients with Beckwith-Wiedemann syndrome (BWS) and almost all pUPDs are segmental isodisomic pUPDs resulting from mitotic recombination at an early embryonic stage. A mechanism initiating a DNA double strand break (DSB) within 11p has been predicted to lead to segmental pUPD. However, no consensus motif has yet been found. Here, we analyzed 32 BWS patients with pUPD by SNP array and searched for consensus motifs. We identified four consensus motifs frequently appearing within breakpoint regions of segmental pUPD. These motifs were found in another nine BWS patients with pUPD. In addition, the seven motifs found in meiotic recombination hot spots could not be found within pUPD breakpoint regions. Histone H3 lysine 4 trimethylation, a marker of DSB initiation, could not be found either. These findings suggest that the mechanism(s) of mitotic recombination leading to segmental pUPD are different from that of meiotic recombination. Furthermore, we found seven patients with paternal uniparental diploidy (PUD) mosaicism. Comparison of clinical features between segmental pUPDs and PUDs showed that developmental disability and cardiac abnormalities were additional characteristic features of PUD mosaicism, along with high risk of tumor development. We also found that macroglossia was characteristic of segmental pUPD mosaicism.
authors.affiliation: Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Department of Pediatrics, Faculty of Medicine, Saga University, Saga 849-8501, Japan.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Ohtsuka
authors.affiliation: Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine.
authors.forename: Ken
authors.initials: K
authors.lastname: Higashimoto
authors.affiliation: World Fusion Co., Ltd., Tokyo 103-0013, Japan and.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Oka
authors.affiliation: Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Yatsuki
authors.affiliation: Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Jozaki
authors.affiliation: Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Department of Pediatrics, Faculty of Medicine, Saga University, Saga 849-8501, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Maeda
authors.affiliation: World Fusion Co., Ltd., Tokyo 103-0013, Japan and.
authors.forename: Kozo
authors.initials: K
authors.lastname: Kawahara
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Saga University, Saga 849-8501, Japan.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Hamasaki
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Saga University, Saga 849-8501, Japan.
authors.forename: Muneaki
authors.initials: M
authors.lastname: Matsuo
authors.affiliation: Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nishioka
authors.affiliation: Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Joh
authors.affiliation: Nishikyushu University, Kanzaki 842-8585, Japan.
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Mukai
authors.affiliation: Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, soejimah@cc.saga-u.ac.jp.
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Soejima
mesh_terms: D001506:Beckwith-Wiedemann Syndrome; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008938:Mitosis; D009030:Mosaicism; D011995:Recombination, Genetic; D024182:Uniparental Disomy / Q000209:etiology / Q000235:genetics*