{
  "abstract": "The C9orf72 hexanucleotide repeat expansion (HRE) is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). It follows autosomal dominant inheritance in families, however, a high proportion of cases are sporadic, raising the possibility of parental premutation. We have demonstrated that intermediate-length alleles (IAs) with >18 repeats (allele frequency ~1%) belong to the same pool of haplotypes as the HRE, suggesting shared ancestry. Here, we tested whether alleles with >18 repeats expand in parental transmission. We used two repeat-primed PCR methods to analyze allele lengths in 539 genetically unselected parent-offspring pairs and in 152 pairs known to carry the SNP (rs139185008*C) that tags >18 repeat IAs and the HRE in Finland. We discovered intergenerational repeat length changes only in >20 repeat alleles. A significant (P = 0.0059) sex bias in 6-40 repeat alleles was noted using a logistic regression model. In this allele range, 12 out of 16 expansions were paternally inherited and 6 out of 7 contractions were maternally inherited. The expansion rate of 20-40 repeat alleles was 34 % in paternal and 11 % in maternal transmissions. In the 20-40 repeat range, most intergenerational expansions were 1-4 repeats in size (15/16), but one larger jump, a paternal expansion from 27 to 73 repeats, was observed. These results demonstrate that alleles with >20 repeats have an increased likelihood of instability, that a paternal expansion bias is observed in alleles with 20-40 repeats, and that expansion events are predominantly 1-4 repeats in size.",
  "abstract_shown": true,
  "affiliations": [
    "University of Helsinki"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "O. S. Rautila"
    },
    {
      "name": "A. Kiviharju"
    },
    {
      "name": "L. Jansson"
    },
    {
      "name": "FinnGen"
    },
    {
      "name": "K. Kaivola"
    },
    {
      "name": "P. J. Tienari"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ad79ffd0dp3z1.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.10.750611",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.10.750611v1.full",
  "id": "ad79ffd0dp3z1",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.10.750611v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "genetics"
    ],
    [
      "openalex",
      "2728|Amyotrophic Lateral Sclerosis Research"
    ]
  ],
  "openalex": "W7213265060",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.10.750611v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-10",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ad79ffd0dp3z1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:35Z",
      "native_id": "10.64898/2026.09.10.750611",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.10.750611v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:genetics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Intergenerational instability of the C9orf72 hexanucleotide repeat",
  "title_text": "Intergenerational instability of the C9orf72 hexanucleotide repeat",
  "type": "preprint",
  "updated_at": "2026-10-30T12:22:35Z",
  "url": "https://research.draconitic.com/paper/ad79ffd0dp3z1",
  "venue": "bioRxiv",
  "versions": []
}