Pseudogenes in Human Cancer

Poliseno, Laura; Marranci, Andrea; Pandolfi, Pier Paolo

doi:10.3389/fmed.2015.00068

Cited by 98 publications

(105 citation statements)

References 57 publications

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“…Many of the B-derived transcripts might be functionless because the gene copies on the B chromosome are incomplete, so that their translation would yield anomalous polypeptides which could potentially pose metabolic stress on cells. Alternatively, these gene fragments could interfere A chromosome gene expression by competitively binding transcription factors383940. However, we cannot rule out that the transcripts from some B-located genes, being apparently complete, can be functional, as previously observed for 45S rRNA transcripts18.…”

Section: Discussionmentioning

confidence: 73%

Protein-coding genes in B chromosomes of the grasshopper Eyprepocnemis plorans

Navarro-Domínguez

Ruiz‐Ruano

Cabrero

et al. 2017

Sci Rep

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For many years, parasitic B chromosomes have been considered genetically inert elements. Here we show the presence of ten protein-coding genes in the B chromosome of the grasshopper Eyprepocnemis plorans. Four of these genes (CIP2A, GTPB6, KIF20A, and MTG1) were complete in the B chromosome whereas the six remaining (CKAP2, CAP-G, HYI, MYCB2, SLIT and TOP2A) were truncated. Five of these genes (CIP2A, CKAP2, CAP-G, KIF20A, and MYCB2) were significantly up-regulated in B-carrying individuals, as expected if they were actively transcribed from the B chromosome. This conclusion is supported by three truncated genes (CKAP2, CAP-G and MYCB2) which showed up-regulation only in the regions being present in the B chromosome. Our results indicate that B chromosomes are not so silenced as was hitherto believed. Interestingly, the five active genes in the B chromosome code for functions related with cell division, which is the main arena where B chromosome destiny is played. This suggests that B chromosome evolutionary success can lie on its gene content.

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Section: Discussionmentioning

confidence: 73%

Protein-coding genes in B chromosomes of the grasshopper Eyprepocnemis plorans

Navarro-Domínguez

Ruiz‐Ruano

Cabrero

et al. 2017

Sci Rep

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“…It is possible that expressed pseudogenes, which are a product of sequence degeneration around the M-factor, are involved, if two copies are sufficient to cause deleterious effects. There is growing evidence for the causal link of pseudogene expression with disease (Poliseno et al, 2015). ( If the missing non-sex-specific region carries a gene essential and haplosufficient for embryo development, individuals lacking the region would die (Figure 3d).…”

Section: Male Lethalitymentioning

confidence: 99%

The sex locus is tightly linked to factors conferring sex-specific lethal effects in the mosquito Aedes aegypti

et al. 2016

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In many taxa, sex chromosomes are heteromorphic and largely non-recombining. Evolutionary models predict that spread of recombination suppression on the Y chromosome is fueled by the accumulation of sexually antagonistic alleles in close linkage to the sex determination region. However, empirical evidence for the existence of sexually antagonistic alleles is scarce. In the mosquito Aedes aegypti, the sex-determining chromosomes are homomorphic. The region of suppressed recombination, which surrounds the male-specific sex-determining gene, remains very small, despite ancient origin of the sex chromosomes in the Aedes lineage. We conducted a genetic analysis of the A. aegypti chromosome region tightly linked to the sex locus. We used a strain with an enhanced green fluorescent protein (EGFP)-tagged transgene inserted near the male-determining gene to monitor crossing-over events close to the boundary of the sex-determining region (SDR), and to trace the inheritance pattern of the transgene in relation to sex. In a series of crossing experiments involving individuals with a recombinant sex chromosome we found developmental abnormalities leading to 1:2 sex biases, caused by lethality of half of the male or female progeny. Our results suggest that various factors causing sex-specific lethal effects are clustered within the neighborhood of the SDR, which in the affected sex are likely lost or gained through recombination, leading to death. These may include genes that are recessive lethal, vital for development and/or sexually antagonistic. The sex chromosome fragment in question represents a fascinating test case for the analysis of processes that shape stable boundaries of a non-recombining region.

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“…Because pseudogenes are not subject to selective pressure, their mutation rate is much higher than that of the functional genes from which they originate, and therefore their unintended sequencing can lead to false positive variant calls [31]. Target enrichment strategies and data analysis are particularly important to avoid interference of pseudogenes in NGS, allowing reliable detection of true pathogenic variations [31]. In our study, in order to avoid forcing alignment of possible amplified pseudogene regions on the NF1 sequence, reads were aligned against the whole human genome and only high-quality reads (Q ≥ 20) were aligned to the reference sequence.…”

Section: Discussionmentioning

confidence: 99%

Hybridization Capture-Based Next-Generation Sequencing to Evaluate Coding Sequence and Deep Intronic Mutations in the NF1 Gene

Cunha

Oliveira

Silva

et al. 2016

Genes

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Neurofibromatosis 1 (NF1) is one of the most common genetic disorders and is caused by mutations in the NF1 gene. NF1 gene mutational analysis presents a considerable challenge because of its large size, existence of highly homologous pseudogenes located throughout the human genome, absence of mutational hotspots, and diversity of mutations types, including deep intronic splicing mutations. We aimed to evaluate the use of hybridization capture-based next-generation sequencing to screen coding and noncoding NF1 regions. Hybridization capture-based next-generation sequencing, with genomic DNA as starting material, was used to sequence the whole NF1 gene (exons and introns) from 11 unrelated individuals and 1 relative, who all had NF1. All of them met the NF1 clinical diagnostic criteria. We showed a mutation detection rate of 91% (10 out of 11). We identified eight recurrent and two novel mutations, which were all confirmed by Sanger methodology. In the Sanger sequencing confirmation, we also included another three relatives with NF1. Splicing alterations accounted for 50% of the mutations. One of them was caused by a deep intronic mutation (c.1260 + 1604A > G). Frameshift truncation and missense mutations corresponded to 30% and 20% of the pathogenic variants, respectively. In conclusion, we show the use of a simple and fast approach to screen, at once, the entire NF1 gene (exons and introns) for different types of pathogenic variations, including the deep intronic splicing mutations.

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Pseudogenes in Human Cancer

Cited by 98 publications

References 57 publications

Protein-coding genes in B chromosomes of the grasshopper Eyprepocnemis plorans

Protein-coding genes in B chromosomes of the grasshopper Eyprepocnemis plorans

The sex locus is tightly linked to factors conferring sex-specific lethal effects in the mosquito Aedes aegypti

Hybridization Capture-Based Next-Generation Sequencing to Evaluate Coding Sequence and Deep Intronic Mutations in the NF1 Gene

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