PacBio SMRT sequencing resolves complex alpha-globin structural variants

In our study, addressing the diagnostic pitfall of conventional methods (Gap-PCR, MLPA), which indiscriminately classify numerous cases as "-alpha3.7/alphaalpha" due to an inability to resolve complex rearrangements, this study employed Single-Molecule Real-Time sequencing for precise genotyping. We successfully identified the hidden true genotypes in these samples, including HKalphaalpha/alphaalpha, -alpha3.7/alphaalphaalphaanti4.2, HKalphaalpha/-alpha3.7, -alpha3.7/alphaalphaalphaanti3.7, and -alpha3.7/alphaalpha12. This breakthrough not only rectifies misinterpretations from traditional methods but also provides a critical foundation for precise clinical genetic counseling and offspring risk assessment.