Insight into the mechanisms and consequences of recurrent telomere capture associated with a sub-telomeric deletion

Autor(es)

dos Santos, Alexsandro ^[1] ; Campagnari, Francine ^[1] ; Victorino Krepischi, Ana Cristina ^[1] ; Ribeiro Camara, Maria de Lourdes ^[2] ; de Arruda Brasil, Rita de Cassia E. ^[2] ; Vieira, Ligia ^[1] ; Vianna-Morgante, Angela M. ^[1] ; Otto, Paulo A. ^[1] ; Pearson, Peter L. ^[1] ; Rosenberg, Carla ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Genet & Evolutionary Biol, Inst Biosci, Rua Matao 277, BR-05508090 Sao Paulo, SP - Brazil

^[2] Sao Paulo State Univ, Fac Odontol, Ctr Odontol Assistance Patients Special Needs, Rodovia Marechal Rondon Km 528, BR-16018395 Aracatuba, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Chromosome Research; v. 26, n. 3, p. 191-198, SEP 2018.
• Citações Web of Science: 1

Resumo

A complex mosaicism of the short arm of chromosome 1 detected by SNP microarray analysis is described in a patient presenting a 4-Mb 1p36 terminal deletion and associated phenotypic features. The array pattern of chromosome 1p displayed an intriguing increase in divergence of the SNP heterozygote frequency from the expected 50% from the centromere towards the 1p36 breakpoint. This suggests that various overlapping segments of UPD were derived by somatic recombination between the 1p homologues. The most likely explanation was the occurrence of a series of events initiated in either a gamete or an early embryonic cell division involving a 1pter deletion rapidly followed by multiple telomere captures, resulting in additive, stepped increases in frequency of homozygosity towards the telomere. The largest segment involved the entire 1p, and at least four other capture events were observed, indicating that at least five independent telomere captures occurred in separate cell lineages. The determination of breakpoint position by detection of abrupt changes in B-allele frequency using a moving window analysis demonstrated that they were identical in blood and saliva, the tissues available for analysis. We developed a model to explain the interaction of parameters determining the mosaic clones and concluded that, while number, size, and position of telomere captures were important initiating determinants, variation in individual clone frequencies was the main contributor to mosaic differences between tissues. All previous reports of telomere capture have been restricted to single events. Other cases involving multiple telomere capture probably exist but require investigation by SNP microarrays for their detection. (AU)

• Processo FAPESP: 12/50981-5 - Uso de arrays genômicos de alta resolução e next generation sequencing no diagnóstico de deficiência mental e anomalias congênitas
• Beneficiário: Francine Campagnari Guilhem
• Modalidade de apoio: Auxílio à Pesquisa - Pesquisa Inovativa em Pequenas Empresas - PIPE
• Processo FAPESP: 13/08028-1 - CEGH-CEL - Centro de Estudos do Genoma Humano e de Células-Tronco
• Beneficiário: Mayana Zatz
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs