STR calling and interpretation

Calling methodology

Emedgene uses ExpansionHunter by DRAGEN to call short tandem repeats (STR), also known as repeats expansions.

Thirty clinical genes associated with diseases caused by repeat expansion are called in DRAGEN version 3.9 and presented in the platform. Those genes are: AFF2, AR, ATN1, ATXN1, ATXN10, ATXN2, ATXN3, ATXN7, ATXN8OS, C9ORF72, CACNA1A, CBL, CNBP, CSTB, DIP2B, DMPK, FMR1, FXN, GIPC1, GLS, HTT, JPH3, NIPA1, NOP56, PABPN1, PHOX2B, PPP2R2B, RFC1, TBP, TCF4.

STR calling with ExpansionHunter

Spanning reads

Exact sizes of short repeats are identified from spanning reads that completely contain the repeat sequence.

Flanking reads

When the repeat length is close to the read length, the size of the repeat is approximated from the flanking reads that partially overlap the repeat and one of the repeat flanks.

In-repeat reads (IRRs)

If the repeat is longer than the read length, its size is estimated from reads completely contained inside the repeat (in-repeat reads). In-repeat reads anchored by their mate to the repeat region are used to estimate the size of the repeat up to the fragment length. When there is no evidence of long repeats with the same repeat motif elsewhere in the genome, pairs of in-repeat reads can also be used to estimate the size of long (greater-than-fragment-length) repeats.

Recommendation for interpretation

In light of our recent experience and an internal investigation by the Illumina’s scientific team, we believe it is appropriate to enable prioritization for a subset of STR loci, but not all loci typed by DRAGEN. This is due to technical genotyping challenges and/or lack of scientific evidence of pathogenicity for the remaining loci. Current list of genes where STR may be tagged when appropriate is provided below: