Constitutional translocation breakpoint mapping by genome-wide paired-end sequencing identifies HACE1 as a putative Wilms tumour susceptibility gene

  title={Constitutional translocation breakpoint mapping by genome-wide paired-end sequencing identifies HACE1 as a putative Wilms tumour susceptibility gene},
  author={Ingrid Slade and Philip J. Stephens and Jessica Douglas and Karen T. Barker and Lucy A. Stebbings and Fatemeh Abbaszadeh and Kathryn Pritchard-Jones and Regina Cole and Barry L. Pizer and Charles A Stiller and Gordan M. Vujani{\'c} and Richard H. Scott and Michael R. Stratton and Nazneen Rahman},
  journal={Journal of Medical Genetics},
  pages={342 - 347}
Background Localisation of the breakpoints of chromosomal translocations has aided the discovery of several disease genes but has traditionally required laborious investigation of chromosomes by fluorescent in situ hybridisation approaches. Here, a strategy that utilises genome-wide paired-end massively parallel DNA sequencing to rapidly map translocation breakpoints is reported. This method was used to fine map a de novo t(5;6)(q21;q21) translocation in a child with bilateral, young-onset… 

Breakpoint mapping by next generation sequencing reveals causative gene disruption in patients carrying apparently balanced chromosome rearrangements with intellectual deficiency and/or congenital malformations

Next generation sequencing (NGS) was used to locate breakpoints at the molecular level in four patients with multiple congenital abnormalities and/or intellectual deficiency who were carrying ABCR and showed that in three out of four patients, gene disruption could account for the phenotype.

Chromothripsis as a mechanism driving complex de novo structural rearrangements in the germline.

The pattern of random joining of chromosomal fragments that is observed here strongly resembles the somatic rearrangement patterns--termed chromothripsis--that have recently been described in deranged cancer cells and it is concluded that a similar mechanism may also drive the formation of de novo structural variation in the germline.

Characterising chromosome rearrangements: recent technical advances in molecular cytogenetics

This work describes how array-based comparative genomic hybridisation, SNP arrays, array painting and next-generation sequencing analytical methods allow the extensive characterisation of chromosome rearrangements in human genomes.

Genomic Investigation of Balanced Chromosomal Rearrangements in Patients with Abnormal Phenotypes

Follow-up of BCR carriers would improve the knowledge about these chromosomal rearrangements and their consequences, and contribute to the characterization of this type of chromosome rearrangement and to the phenotype-genotype correlation.

Deciphering the pathogenic consequences of chromosomal aberrations in human genetic disease

Current methods for breakpoint identification and their impact on the interpretation of chromosome aberrations in patients with MCA/MR are reviewed and opportunities to dissect disease mechanisms based on large-scale genomic technologies and studies in model organisms are discussed.

Genetic and epigenetic analyses guided by high resolution whole-genome SNP array reveals a possible role of CHEK2 in Wilms tumour susceptibility

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Molecular logic underlying chromosomal translocations, random or non-random?

Identification of disrupted AUTS2 and EPHA6 genes by array painting in a patient carrying a de novo balanced translocation t(3;7) with intellectual disability and neurodevelopment disorder

The hypothesis that the likely chromosomal mechanism responsible for the translocation could be due either to replicative stress or to recombination‐based mechanisms is put forward.

Absence of the TRIP13 c.1060C>T Mutation in Wilms Tumor Patients From Pakistan

The findings suggest that TRIP13 c.1060C>T mutation may be infrequent in Pakistani WT cases, and further evaluation in a large number of WT patients of Kashmiri heritage and various ethnic backgrounds from Pakistan is warranted.



Mapping translocation breakpoints by next-generation sequencing.

Shooting shotgun sequencing of flow-sorted derivative chromosomes using "next-generation" (Illumina/Solexa) multiplex sequencing-by-synthesis technology will greatly facilitate large-scale breakpoint mapping and gene finding in patients with disease-associated balanced translocations.

Physical localisation of the breakpoints of a constitutional translocation t(5;6)(q21;q21) in a child with bilateral Wilms' tumour.

The translocation breakpoints between YAC clones on each chromosome arm are physically defined using fluorescence in situ hybridisation on metaphase preparations of MA214L and this is the first report of these chromosomal regions being implicated in Wilms' tumourigenesis.

Paired-End Mapping Reveals Extensive Structural Variation in the Human Genome

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Identification of somatically acquired rearrangements in cancer using genome-wide massively parallel paired-end sequencing

The results demonstrate the feasibility of systematic, genome-wide characterization of rearrangements in complex human cancer genomes, raising the prospect of a new harvest of genes associated with cancer using this strategy.

The parathyroid hormone-responsive B1 gene is interrupted by a t(1;7)(q42;p15) breakpoint associated with Wilms' tumour

The disruption of PTH-B1 by the t(1;7), together with aberrant splicing in sporadic WTs, suggests that PTH -B1 is a candidate for the 7p Wilms' tumour suppressor gene.

Localization of a novel t(1;7) translocation associated with Wilms' tumor predisposition and skeletal abnormalities

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