Long-read sequencing identifies copy-specific markers of SMN gene conversion in spinal muscular atrophy.

ABSTRACT:

Background

The complex 2 Mb survival motor neuron (SMN) locus on chromosome 5q13, including the spinal muscular atrophy (SMA)-causing gene SMN1 and modifier SMN2, remains incompletely resolved due to numerous segmental duplications. Variation in SMN2 copy number, presumably influenced by SMN1 to SMN2 gene conversion, affects disease severity, though SMN2 copy number alone has insufficient prognostic value due to limited genotype-phenotype correlations. With advancements in newborn screening and SMN-targeted therapies, identifying genetic markers to predict disease progression and treatment response is crucial. Progress has thus far been limited by methodological constraints.

Methods

To address this, we developed HapSMA, a method to perform polyploid phasing of the SMN locus

SUBMITTER: Zwartkruis MM 

PROVIDER: S-EPMC11927269 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature