Identification and Characterization of New Alu Element Insertion in the BRCA1 Exon 14 Associated with Hereditary Breast and Ovarian Cancer

Bouras, Ahmed Fouad; Léoné, Mélanie; Bonadona, Valérie; Lebrun, Marine; Calender, Alain; Boutry‐Kryza, Nadia

doi:10.3390/genes12111736

Cited by 5 publications

(2 citation statements)

References 17 publications

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“… 23 Alu insertions often cause disease by disrupting a coding region or a splice signal. For example, Alu insertions in BRCA1 can cause hereditary breast cancer, 24 and Alu insertions in GLA can cause cardiac diseases. 25 Although we do not yet have evidence that the AluYb8 insertion in the 3' UTR of the risk haplotype has a functional impact on the TMEM106B gene in this haplotype, the 3'UTR region of genes often plays a role in transcriptional regulation 26 and this insertion may impact the expression of protein from this transcript.…”

Section: Discussionmentioning

confidence: 99%

A common Alu insertion in the 3'UTR of TMEM106B is associated with risk of dementia

Rodney,

Karanjeet,

Benzow

et al. 2024

Alzheimer's & Dementia

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INTRODUCTIONSequence variants in TMEM106B have been associated with an increased risk of developing dementia.METHODSAs part of our efforts to generate a set of mouse lines in which we replaced the mouse Tmem106b gene with a human TMEM106B gene comprised of either a risk or protective haplotype, we conducted an in‐depth sequence analysis of these alleles. We also analyzed transcribed TMEM106B sequences using RNA‐seq data (AD Knowledge portal) and full genome sequences (1000 Genomes).RESULTSWe identified an AluYb8 insertion in the 3' untranslated region (3'UTR) of the TMEM106B risk haplotype. We found this AluYb8 insertion in every risk haplotype analyzed, but not in either protective haplotypes or in non‐human primates.DISCUSSIONWe conclude that this risk haplotype arose early in human development with a single Alu‐insertion event within a unique haplotype context. This AluYb8 element may act as a functional variant in conferring an increased risk of developing dementia.Highlights We conducted an in‐depth sequence analysis of (1) a risk and (2) a protective haplotype of the human TMEM106B gene. We also analyzed transcribed TMEM106B sequences using RNA‐seq data (AD Knowledge Portal) and full genome sequences (1000 Genomes). We identified an AluYb8 insertion in the 3' untranslated region (3'UTR) of the TMEM106B risk haplotype. We found this AluYb8 insertion in every risk haplotype analyzed, but not in either protective haplotypes or in non‐human primates. This AluYb8 element may act as a functional variant in conferring an increased risk of developing dementia.

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Section: Discussionmentioning

confidence: 99%

A common Alu insertion in the 3'UTR of TMEM106B is associated with risk of dementia

Rodney,

Karanjeet,

Benzow

et al. 2024

Alzheimer's & Dementia

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“…Alu insertions often cause disease by disrupting a coding region or a splice signal. For example, Alu insertions in BRCA1 can cause hereditary breast cancer 16 , and Alu insertions in GLA can cause cardiac diseases 17 .…”

Section: Discussionmentioning

confidence: 99%

A common Alu element insertion in the 3’UTR ofTMEM106Bis associated with an increased risk of dementia

Rodney,

Karanjeet,

Benzow

et al. 2023

Preprint

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Sequence variants inTMEM106Bhave been associated with an increased risk of developing several different types of dementia. As part of our efforts to generate a set of mouse lines in which we replaced the mouseTmem106bgene with a humanTMEM106Bgene comprised of either a risk or protective haplotype, we conducted an in-depth sequence analysis of these alleles. We identified an AluYb8 insertion in the 3’ untranslated region (3’UTR) of theTMEM106Brisk haplotype. We analyzed transcribedTMEM106Bsequences using RNA-seq data available through the AD Knowledge portal and full genome sequences from the 1000Genomes databases and found that every risk allele analyzed shares this same AluYb8 insertion. The allele frequency of the risk haplotype ranges from 26% to 60% in the populations examined, and the balance of the alleles in each population is the protective haplotype. The primary sequence features of both haplotypes are distinct from the variants found in other primates. We conclude that the risk haplotype arose early in human development with a single Alu-insertion event within a unique haplotype context. Together these two non-ancestral allele variant types now appear to constitute the vast majority of theTMEM106Balleles but neither has come to fully predominate in any modern human population.

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Spectrum and genotyping strategies of “dark” genetic matter in germline susceptibility genes of tumor syndromes

Bozsik,

Butz,

Grolmusz

et al. 2025

Critical Reviews in Oncology/Hematology

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Identification and Characterization of New Alu Element Insertion in the BRCA1 Exon 14 Associated with Hereditary Breast and Ovarian Cancer

Cited by 5 publications

References 17 publications

A common Alu insertion in the 3'UTR of TMEM106B is associated with risk of dementia

A common Alu insertion in the 3'UTR of TMEM106B is associated with risk of dementia

A common Alu element insertion in the 3’UTR ofTMEM106Bis associated with an increased risk of dementia

Spectrum and genotyping strategies of “dark” genetic matter in germline susceptibility genes of tumor syndromes

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