Evaluating scientific and ethical approaches to newborn screening with whole genome sequencing using large-scale population cohorts

现在，英国所有的婴儿在出生时都要通过新生儿血液抽查来筛查九种可治疗的疾病。然而，存在着更多非常罕见但也可以治疗的遗传疾病。在某些情况下，出生后不久及早发现和治疗可以预防疾病的发生，从而为个人、家庭和社会带来巨大的终身好处。现在，只需一次测试，就可以对一个人(整个基因组)的所有DNA进行排序，并确定他们的整个基因构成。这项技术提供了同时检测和预防多种遗传疾病的机会。专家小组目前正在努力决定哪些疾病和基因适合使用全基因组测序在新生儿中进行筛查。然而，最大的挑战之一是，DNA序列的变化可能会对不同的人产生不同的影响，因此在一个家庭中导致疾病的变化可能对另一个家庭没有影响。发现不会导致婴儿患病的基因变化对父母来说是非常痛苦的，并导致医疗服务的不必要的额外工作。我们正试图通过观察英国20多万名已经完成基因组测序的人来缓解这个问题。其中一些基因组来自自愿帮助医学研究的健康成年人，另一些来自病情严重的婴儿。我们将研究以前与可治疗的儿童疾病有关的基因，并比较我们在健康成年人和患病婴儿中发现的基因变化类型的数量。我们也会查看他们的住院记录和医疗记录，看看他们是否患有这种疾病。此外，我们亦会向专家和市民进行调查，以进一步了解与这类测试有关的主要道德问题。我们尤其热衷于探讨对大规模增加新生儿筛查中包括的疾病数量的态度，这可能会导致更多的假阳性结果。这项研究将有助于决定哪些基因和条件应该在新生儿身上进行筛查，哪些不应该。通过与英国基因组公司和英国国民健康保险制度合作，我们将努力确保我们的研究被用于改善健康和维护患者安全。

All babies in the UK are now screened at birth for nine treatable diseases through the newborn blood spot test. However, many more genetic conditions exist that are very rare but also treatable. In some cases, early detection and treatment shortly after birth can prevent the disease from occurring, thus offering enormous and life-long benefits to individuals, families, and society. It is now possible to sequence all the DNA from an individual (a whole genome) and determine their entire genetic makeup with just one test. This technology offers the opportunity to detect and prevent many genetic conditions at the same time. Expert groups are now working to decide which diseases and genes are suitable to screen in newborn babies using whole genome sequencing. However, one of the biggest challenges is that changes to the DNA sequence can have different effects in different people, so a change that causes disease in one family may have no effect in another. Finding genetic changes that don't cause disease in babies would be extremely distressing for parents and result in unnecessary extra work for healthcare services. We are trying to lessen this problem by looking at more than 200,000 people in the UK that have already had their genome sequenced. Some of these genomes are from healthy adults, who volunteered to help with medical research, while others are from very sick babies. We will look at genes that have been linked to treatable childhood diseases before and compare the number of types of genetic changes we find in healthy adults versus sick babies. We will also look at their hospital notes and medical records to see if they have the disease. In addition, we will survey experts and members of the public to better understand the key ethical issues relating to this kind of testing. We are particularly keen to explore attitudes towards massively increasing the number of diseases included in newborn screening, which could lead to more false positive results. This research will help decide which genes and conditions should be screened for in newborns, and which should not. By working with Genomics England and NHS England, we will work make sure that our research is used to improve health and maintain patient safety.