{
  "abstract": "Huntington’s disease (HD) is a neurodegenerative disease characterised by paternal anticipation in some families: disease severity worsens across generations due to expansion of the CAG repeat in the huntingtin (HTT) gene. Larger HTT-CAG repeat is associated with earlier onset of symptoms. HD progression is characterised by somatic HTT-CAG expansion in brain.This study aims to measure and characterise HTT-CAG repeat variability in germline (sperm) and somatic cells (blood) of people with HD, identify factors which influence this variability, and explore the potential of sperm as a biomarker of HTT-CAG repeat variability.We are conducting a prospective cohort study of 120 men aged 18-65 years with ≥40 CAG repeats. A germline-specific DNA extraction method has been developed. Targeted sequencing of the HTT repeat using MiSeq enables quantification of repeat variability. Preliminary findings indicate sperm exhibits greater HTT-CAG repeat variability than blood, and higher instability with greater baseline CAG size.This underscores the potential of semen as a valuable biofluid for investigating the genetic mechanisms that underscore genetic anticipation, and its potential as a biomarker of HTT-CAG repeat variability. Future research aims to investigate change in sperm-CAG variability at one-year follow-up, and to perform genetic analyses to identify variants that influence this.catrin.medicine@gmail.com",
  "authors": [
    {
      "affiliations": [
        "Queen Square Institute of Neurology, University College London, London, UK"
      ],
      "name": "Sohrabi Catrin"
    },
    {
      "affiliations": [
        "Queen Square Institute of Neurology, University College London, London, UK"
      ],
      "name": "Rajagopal Sangeerthana"
    },
    {
      "affiliations": [
        "Queen Square Institute of Neurology, University College London, London, UK"
      ],
      "name": "Merrall Alice"
    },
    {
      "affiliations": [
        "CHDI Foundation, USA"
      ],
      "name": "Kalinava Natallia"
    },
    {
      "affiliations": [
        "School of Molecular Biosciences, University of Glasgow, UK"
      ],
      "name": "Ciosi Marc"
    },
    {
      "affiliations": [
        "Queen Square Institute of Neurology, University College London, London, UK"
      ],
      "name": "Tabrizi Sarah J"
    },
    {
      "affiliations": [
        "CHDI Foundation, USA"
      ],
      "name": "Sampaio Cristina"
    },
    {
      "affiliations": [
        "School of Molecular Biosciences, University of Glasgow, UK"
      ],
      "name": "Monckton Darren"
    },
    {
      "affiliations": [
        "CHDI Foundation, USA"
      ],
      "name": "Wilkinson Hilary"
    },
    {
      "affiliations": [
        "Queen Square Institute of Neurology, University College London, London, UK"
      ],
      "name": "Hensman Moss Davina J"
    }
  ],
  "title": "186 Investigating genetic anticipation in huntington’s disease by studying sperm HTT-CAG variability in HTT expansion-carriers",
  "uid": "00cd876e-250e-5551-b346-2d48e2b63d6b"
}