Transposon insertion profiling by sequencing (TIPseq) identifies novel LINE-1 insertions in human sperm

Thalita S. Berteli, Fang Wang, Wilson McKerrow, Paula A. Navarro, David Fenyo, Jef D. Boeke, Fabiana B. Kohlrausch, David L. Keefe

Research output: Contribution to journalArticlepeer-review


Purpose: Long interspersed nuclear element-1 (LINE-1 or L1) comprises 17% of the human genome. Retrotransposons may perturb gene integrity or alter gene expression by altering regulatory regions in the genome. The germline employs a number of mechanisms, including cytosine methylation, to repress retrotransposon transcription throughout most of life. Demethylation during germ cell and early embryo development de-represses retrotransposons. Intriguingly, de novo genetic variation appearing in sperm has been implicated in a number of disorders in offspring, including autism spectrum disorder, schizophrenia, and bipolar disorder. We hypothesize that human sperm exhibit de novo retrotransposition and employ a new sequencing method, single cell transposon insertion profiling by sequencing (scTIPseq) to map them in small amounts of human sperm. Methods: Cross-sectional case–control study of sperm samples (n=10 men; ages 32–55 years old) from consenting men undergoing IVF at NYU Langone Fertility Center. scTIPseq identified novel LINE-1 insertions in individual sperm and TIPseqHunter, a custom bioinformatics pipeline, compared the architecture of sperm LINE-1 to known LINE-1 insertions from the European database of Human specific LINE-1 (L1Hs) retrotransposon insertions (euL1db). Results: scTIPseq identified 17 novel insertions in sperm. New insertions were mainly intergenic or intronic. Only one sample did not exhibit new insertions. The location or number of novel insertions did not differ by paternal age. Conclusion: This study for the first time reports novel LINE-1 insertions in human sperm, demonstrating the feasibility of scTIPseq, and identifies new contributors to genetic diversity in the human germ line.

Original languageEnglish (US)
Pages (from-to)1835-1843
Number of pages9
JournalJournal of Assisted Reproduction and Genetics
Issue number8
StatePublished - Aug 2023


  • Aging
  • Human sperm
  • LINE-1
  • TIPseq

ASJC Scopus subject areas

  • Reproductive Medicine
  • Genetics
  • Obstetrics and Gynecology
  • Developmental Biology
  • Genetics(clinical)


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