Alpha Satellite Insertion Close to an Ancestral Centromeric Region

Area of Science:

• Genetics and Genomics
• Molecular Biology
• Human Evolution

Background:

• Human centromeres are primarily composed of alpha satellite DNA organized into higher-order repeats (HORs).
• Alpha satellite DNA exhibits dynamic behavior, including sequence homogenization and relocation, particularly during new centromere formation.

Purpose of the Study:

• To characterize a de novo insertion of alpha satellite DNA identified during prenatal diagnosis.
• To investigate the functional and evolutionary implications of this alpha satellite DNA rearrangement.

Main Methods:

• Fluorescent in situ hybridization (FISH) for initial identification.
• Centromere protein binding assays (CENP-B, CENP-A) to assess functionality.
• Long-read sequencing and mapping to the T2T-CHM13 human genome assembly.

Main Results:

• A de novo insertion of alpha satellite DNA (D18Z1) from chromosome 18 into chromosome 15q26 was identified.
• The inserted DNA was bound by CENP-B but lacked centromeric functionality (no constriction, no CENP-A binding).
• The insertion, associated with a deletion and enriched in LTRs, occurred in the paternal germline near an ancestral inactive centromeric site.

Conclusions:

• This case represents a new class of structural variation termed 'alpha satellite insertion'.
• The findings expand understanding of alphoid DNA dynamics and suggest potential relocation of centromeric arrays near ancient centromeric sites.