Transposable elements that have recently been mobile in the human genome.

Area of Science:

• Genomics
• Human Genetics
• Molecular Biology

Background:

• Transposable elements (TEs) constitute a significant portion of the human genome, influencing genetic diversity and disease.
• Identifying active TE subfamilies is crucial but lacks consensus.
• A novel statistical method was developed to identify recently mobile subfamilies (RMSs) based on indel overlaps.

Purpose of the Study:

• To develop and apply a novel statistical test for identifying active transposable element subfamilies in the human genome.
• To create a comprehensive catalogue of recently mobile subfamilies (RMSs).
• To investigate the role of RMSs in human genetic disorders and cancer.

Main Methods:

• Developed a novel statistical test for recently mobile subfamilies (RMSs) using polymorphic indel overlap patterns.
• Analyzed >100,000 polymorphic indels to identify RMSs.
• Utilized CRISPR/Cas9 deletion and genome-wide allele-specific expression analysis to assess TE insertion effects.

Main Results:

• Generated a high-confidence catalogue of 20 RMSs, including previously underestimated HERV-K.
• RMSs are significantly enriched in germline genetic disorders and somatic cancer insertions.
• Demonstrated RMS-derived TE insertions impact gene regulation, affecting genes like RPL17 and showing enrichment near allele-specific expression genes.

Conclusions:

• Defined a catalogue of 20 RMSs using a novel statistical approach.
• Highlighted the gene regulatory potential of RMS-derived polymorphic TE insertions.
• Provided a valuable resource for human disease genetics, population history, and understanding TE impact.