CGG short tandem repeat genotype predictions

As expansions of CGG short tandem repeats (STR) are established as the
genetic aetiology of many neurodevelopmental disorders, we aimed to
elucidate the inheritance patterns and role of CGG STRs in autism-spectrum
disorder (ASD). By genotyping 6,063 CGG STR loci in a large cohort of
trios and quads with an ASD-affected proband, we determined an
unprecedented rate of CGG repeat length deviation across a single
generation. While the concept of repeat length being linked to deviation
rate was solidified, we demonstrate how shorter STRs display greater
degrees of size variation. We observed that CGG STRs did not segregate by
Mendelian principles, with a bias against longer repeats, which appeared
to magnify as repeat length increased. Through logistic regression, we
identified 19 genes that displayed significantly higher rates and degrees
of CGG STR expansion within the ASD-affected probands (p < 1 x
10-5). This study not only highlights novel repeat expansions that may
play a role in ASD but also reinforces the hypothesis that CGG STRs are
specifically linked to human cognition.