Mapping the landscape of tandem repeat variability by targeted long read single molecule sequencing in familial X-linked intellectual disability.

Background: The etiology of more than half of all patients with X-linked intellectual disability remains elusive, despite array-based comparative genomic hybridization, whole exome or genome sequencing. Since short read massive parallel sequencing approaches do not allow the detection of larger tandem repeat expansions, we hypothesized that such expansions could be a hidden cause of X-linked intellectual disability.

Methods: We selectively captured over 1800 tandem repeats on the X chromosome and characterized them by long read single molecule sequencing in 3 families with idiopathic X-linked intellectual disability.

Detecting AGG Interruptions in Male and Female FMR1 Premutation Carriers by Single-Molecule Sequencing.

The FMR1 gene contains an unstable CGG repeat in its 5' untranslated region. Premutation alleles range between 55 and 200 repeat units and confer a risk for developing fragile X-associated tremor/ataxia syndrome or fragile X-associated primary ovarian insufficiency. Furthermore, the premutation allele often expands to a full mutation during female germline transmission giving rise to the fragile X syndrome.

Large-scale analysis of tandem repeat variability in the human genome.

Tandem repeats are short DNA sequences that are repeated head-to-tail with a propensity to be variable. They constitute a significant proportion of the human genome, also occurring within coding and regulatory regions. Variation in these repeats can alter the function and/or expression of genes allowing organisms to swiftly adapt to novel environments.