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What does genome editing mean for Down's syndrome?

Professor Robin Lovell-Badge

Group Leader in Stem Cell Biology and Developmental Genetics, Francis Crick Institute

Progress Educational Trust

20 August 2018

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[BioNews, London]

The recent Nuffield Council on Bioethics report 'Genome Editing and Human Reproduction: Social and Ethical Issues' has been both welcomed and criticised.

As is often the case with new reproductive technologies, some critics have raised concerns that new cases of conditions such as Down's syndrome could be eliminated by genome editing, and that the lives of existing people with this condition could be somehow devalued. Is there any factual basis for these concerns?

How might genome editing impact on Down's syndrome?

Most genome editing approaches use an enzyme to cut DNA, and a guide to induce the cut to happen at a designated place in the genome. Cellular mechanisms then usually repair the DNA, and these mechanisms can be enlisted to make quite precise changes, including inactivating or changing specific genes.

In theory, somatic genome editing – that is, making changes to an individual's genome that will not be inherited by any children that individual goes on to have – could be used to address some of the specific traits associated with Down's syndrome by making changes to one copy of a gene. This might help, for example, with the loss of nerve cells that leads to weak muscles, although defining the precise gene(s) responsible for other Down's syndrome traits is difficult.

However, one of the biggest challenges for such somatic uses of genome editing is how to introduce the genome editing components safely and efficiently into the billions of relevant cells in the patient. It will take some time to solve this challenge.

What about using genome editing on the entire extra copy of chromosome 21?

There has been research on iPS (induced pluripotent stem) cells derived from people with Down's syndrome, in which an entire copy of chromosome 21 was either inactivated or completely eliminated, but this was not very efficient.

In theory, such methods could be applied somatically to a fetus or a newborn baby, but it would be difficult to deliver the genome editing components to enough cells for this to be effective.

What about using genome editing on embryos?

The use of genome editing on very early embryos would take us from the realm of somatic genome editing to the realm of germline genome editing – that is, making changes to an individual's genome that could be inherited by any children that this individual goes on to have.

It should be easier to induce loss of an extra chromosome 21 in an early embryo than in a later embryo, because the genome editing components would only need to be introduced into a small number of cells.

The problem is, it is not possible to predict in advance which embryos will have trisomy 21 (that is, an extra copy of chromosome 21). Most cases of Down's syndrome occur de novo, meaning that the condition is genetically 'new' – it is not inherited from the parents. The chance of having child with Down's syndrome increases with maternal age, but never reaches a point where all embryos will inevitably have trisomy 21.

It would be possible (if costly) to check for trisomy 21 using preimplantation genetic testing, taking a few cells from early-stage embryos and screening them for chromosome number before transfer to the prospective mother's womb. But if you have already gone to the trouble of doing this, you can just choose to transfer an embryo that does not have an extra chromosome 21. Genome editing is surplus to requirements.

A special case is parents with Down's syndrome. People with Down's syndrome can have children, and there is a possibility (around 35 percent for women) that their child will inherit the condition. Again, preimplantation genetic testing can be used – and has been used – in such scenarios to avoid transmission of the condition. Again, genome editing is surplus to requirements.

If prospective parents wish to avoid having a child with Down's syndrome, then prenatal testing – particularly noninvasive prenatal testing (NIPT), which uses the small amount of fetal DNA present in the pregnant woman's bloodstream – will remain the most practical option for the foreseeable future. NIPT can be used from 10 weeks in pregnancy to screen for three copies of chromosome 21. Uptake varies between countries, with new cases of Down's syndrome all but disappearing in Iceland and Denmark.


While it is theoretically possible to use germline genome editing to avoid having a child with Down's syndrome, in practice this is – and will almost certainly remain – highly impractical.

More likely, but still some way off becoming reality, is that we will find ways to use somatic genome editing to ameliorate some of the health complications that accompany Down's syndrome. There is evidence that at least some parents of people with Down's syndrome would welcome this possibility.


Analysis of motor dysfunction in Down Syndrome reveals motor neuron degeneration
PLoS Genetics |  10 May 2018
Birth of a healthy child after preimplantation genetic screening of embryos from sperm of a man with non-mosaic Down syndrome
Journal of Assisted Reproduction and Genetics |  3 July 2015
CRISPR/Cas9-mediated targeted chromosome elimination
Genome Biology |  24 November 2017
Gene modification therapies: views of parents of people with Down syndrome
Genetics in Medicine |  21 June 2018
Genome Editing and Human Reproduction: Social and Ethical Issues
Nuffield Council on Bioethics |  17 July 2018
Preferences for prenatal tests for Down syndrome: an international comparison of the views of pregnant women and health professionals
European Journal of Human Genetics |  18 November 2015
Translating dosage compensation to trisomy 21
Nature |  15 August 2013
Trisomy of human chromosome 21 enhances amyloid-β deposition independently of an extra copy of APP
Brain |  26 June 2018

© Copyright Progress Educational Trust

Reproduced with permission from BioNews, an email and online sources of news, information and comment on assisted reproduction and genetics.

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Date Added: 20 August 2018   Date Updated: 20 August 2018
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