Familial retinoblastoma due to intronic LINE-1 insertion causes aberrant and noncanonical mRNA splicing of the RB1 gene

Journal of Human Genetics
Carlos Rodríguez-MartínJavier Alonso

Abstract

Retinoblastoma (RB, MIM 180200) is the paradigm of hereditary cancer. Individuals harboring a constitutional mutation in one allele of the RB1 gene have a high predisposition to develop RB. Here, we present the first case of familial RB caused by a de novo insertion of a full-length long interspersed element-1 (LINE-1) into intron 14 of the RB1 gene that caused a highly heterogeneous splicing pattern of RB1 mRNA. LINE-1 insertion was inferred by mRNA studies and full-length sequenced by massive parallel sequencing. Some of the aberrant mRNAs were produced by noncanonical acceptor splice sites, a new finding that up to date has not been described to occur upon LINE-1 retrotransposition. Our results clearly show that RNA-based strategies have the potential to detect disease-causing transposon insertions. It also confirms that the incorporation of new genetic approaches, such as massive parallel sequencing, contributes to characterize at the sequence level these unique and exceptional genetic alterations.

References

Nov 9, 2001·Annual Review of Genetics·E M Ostertag, H H Kazazian
Apr 19, 2003·Proceedings of the National Academy of Sciences of the United States of America·Brook BrouhaHaig H Kazazian
Dec 21, 2004·Nucleic Acids Research·Tobias PenzkoferTomasz Zemojtel
Feb 15, 2007·European Journal of Human Genetics : EJHG·Catherine DehainaultClaude Houdayer
Sep 12, 2007·Bioinformatics·M A LarkinD G Higgins
Apr 3, 2009·Nucleic Acids Research·François-Olivier DesmetChristophe Béroud
Aug 7, 2010·Advances in Experimental Medicine and Biology·Dietmar Lohmann
Feb 22, 2011·The British Journal of Dermatology·L SamuelovE Sprecher
Jun 10, 2011·Journal of Biosciences·Vidya Latha ParsamChitra Kannabiran
Aug 2, 2011·Annual Review of Genomics and Human Genetics·Christine R BeckJohn V Moran
Nov 30, 2011·PLoS Genetics·Katharina WimmerLudwine Messiaen
Mar 15, 2012·Lancet·Helen DimarasBrenda L Gallie
Nov 15, 2013·Journal of Medical Genetics·Elizabeth A PriceZerrin Onadim

❮ Previous
Next ❯

Citations

May 5, 2017·International Journal of Molecular Sciences·Sumadi Lukman AnwarUlrich Lehmann
Sep 14, 2019·Nature Reviews. Genetics·Lindsay M Payer, Kathleen H Burns
Feb 3, 2021·Mathematical Biosciences and Engineering : MBE·Zhenlei YangRuixi Zhu
Apr 23, 2021·PLoS Genetics·Richard M KeeganJosh Dubnau
Nov 16, 2021·International Journal of Oncology·Michaela Dostalova Merkerova, Zdenek Krejcik
Sep 8, 2021·Molecular Genetics & Genomic Medicine·German DemidovStephan Ossowski

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.