{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T10:59:43Z","timestamp":1767178783306,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.pgen.1009445","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T00:00:00Z","timestamp":1617840000000}}],"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    Expansion of the hexanucleotide repeat (HR) in the first intron of the\n                    <jats:italic>C9orf72<\/jats:italic>\n                    gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in Caucasians. All\n                    <jats:italic>C9orf72<\/jats:italic>\n                    -ALS\/FTD patients share a common risk (R) haplotype. To study\n                    <jats:italic>C9orf72<\/jats:italic>\n                    expression and splicing from the mutant R allele compared to the complementary normal allele in ALS\/FTD patients, we initially created a detailed molecular map of the single nucleotide polymorphism (SNP) signature and the HR length of the various\n                    <jats:italic>C9orf72<\/jats:italic>\n                    haplotypes in Caucasians. We leveraged this map to determine the allelic origin of transcripts per patient, and decipher the effects of pathological and normal HR lengths on\n                    <jats:italic>C9orf72<\/jats:italic>\n                    expression and splicing. In\n                    <jats:italic>C9orf72<\/jats:italic>\n                    ALS patients\u2019 cells, the HR expanded allele, compared to non-R allele, was associated with decreased levels of a downstream initiated transcript variant and increased levels of transcripts initiated upstream of the HR. HR expanded R alleles correlated with high levels of unspliced intron 1 and activation of cryptic donor splice sites along intron 1. Retention of intron 1 was associated with sequential intron 2 retention. The SNP signature of\n                    <jats:italic>C9orf72<\/jats:italic>\n                    haplotypes described here enables allele-specific analysis of transcriptional products and may pave the way to allele-specific therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1009445","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T13:39:01Z","timestamp":1617025141000},"page":"e1009445","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Characterization of C9orf72 haplotypes to evaluate the effects of normal and pathological variations on its expression and 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