Response to the Letter from Garcia-Montojo and colleagues concerning our paper entitled, Quantitative analysis of human endogenous retrovirus-K transcripts in postmortem premotor cortex fails to confirm elevated expression of HERV-K RNA in amyotrophic lateral sclerosis | Acta Neuropathologica Communications | Full Text

Response to the Letter from Garcia-Montojo and colleagues concerning our paper entitled, Quantitative analysis of human endogenous retrovirus-K transcripts in postmortem premotor cortex fails to confirm elevated expression of HERV-K RNA in amyotrophic lateral sclerosis | Acta Neuropathologica Communications | Full Text



Acta Neuropathologica Communications

Response to the Letter from Garcia-Montojo and colleagues concerning our paper entitled, Quantitative analysis of human endogenous retrovirus-K transcripts in postmortem premotor cortex fails to confirm elevated expression of HERV-K RNA in amyotrophic lateral sclerosis

• Jeremy A. GarsonEmail authorView ORCID ID profile,
• Louise Usher,
• Ammar Al-Chalabi,
• Jim Huggett,
• Edmund F. Day and
• Adele L. McCormick

Acta Neuropathologica Communications20197:102

https://doi.org/10.1186/s40478-019-0756-9

©  The Author(s). 2019

• Received: 19 June 2019
• Accepted: 19 June 2019
• Published: 3 July 2019

The original article was published in Acta Neuropathologica Communications 2019 7:101

Keywords

• Amyotrophic lateral sclerosis
• HERV-K
• Human endogenous retroviruses
• RNA
• RT-qPCR

In their Letter to the Editor in this issue, Garcia-Montojo, Li and Nath [5] question several technical aspects of our study recently published in Acta Neuropathologica Communications [6]. Our study, in contrast to an earlier report by Nath’s group [11], failed to find elevated expression of HERV-K RNA in postmortem premotor cortex of patients with amyotrophic lateral sclerosis (ALS). Another study by an independent group [12] also failed to confirm elevated expression of HERV-K RNA in postmortem brain tissue of ALS patients.

There are a total of five technical issues raised by Garcia-Montojo and colleagues in their Letter. Briefly, these are, i) concerns regarding our selection of controls, in particular the number of control subjects with cancer, ii) concerns regarding the number of ALS patients investigated, iii) concerns regarding the RNA integrity numbers (RINs) of the ALS patient tissues and control tissues analysed in our study, iv) concerns regarding our selection of reference genes for RT-qPCR (quantitative real-time reverse transcription polymerase chain reaction) for data normalisation, and v) our use of the RT-qPCR technique rather than alternative methods such as RNA-Seq (whole transcriptome shotgun sequencing by next-generation sequencing) for analysing the postmortem tissue samples. Each of these questions will be considered in turn: