The DNA sequencing lab at the Sanger Institute near Cambridge is about the size of a tennis court. Inside, lined up in rows, are 48 machines with the combined value of four dozen top-end Ferraris. You need to stand close by to hear them work as their clicks and purrs are drowned out by the overhead air conditioning. There is a faint smell of science from the sample preparation room next door and the occasional technician can be seen tending to the machines.
One machine is loaded with the genetic material of 14 children. In a week’s time the DNA sequence of each child will be ready. The child’s entire genome is not required, the 1% that produces protein is enough.
The sequences are being generated to help understand why
the children have not developed quite as they should. The children are part of Deciphering Developmental Disorders project (DDD)
run by the Sanger Institute in partnership with NHS genetics clinics.
Diagnosing children with developmental problems is tricky. Babies develop at different rates and worried parents who present to their GP can be ignored and made to feel over fussy. Jane Gregory, whose daughter Chrissy had developmental delay as a child, was not taken seriously, “I kept badgering our doctors to investigate what could be causing Chrissy’s problems but they treated me like a neurotic first-time mum.” Chrissy is now 27 and spends the week in a long-stay psychiatric assessment and treatment hospital, returning to her Hampshire home for the weekends.
Technology has moved on since Chrissy was a baby, and now doctors have more tools at their fingertips. Most developmental disorders are caused by an error in the child’s DNA sequence so tracking down the mistake can provide a concrete diagnosis. The simplest method is to study the child’s chromosomes under a microscope, but this only identifies large scale faults, for example the duplication of chromosomes leading to Down’s Syndrome.
A further level of detail can be uncovered using microarrays. Instead of looking at full length chromosomes the DNA is broken down into shorter lengths and compared to standards. This technique led to the diagnosis of Chrissy, who was found to have a small deletion in chromosome 1. “I was thrilled,” says her mother Jane, “because I had been searching for answers for years. The diagnosis has changed how I see the future; now I can finally tell people why Chrissy is like she is.”
Only about 30% of developmental errors can be identified this way, the remainder need the might of the DNA sequencing machines. Their fine scale analysis can spot small errors that have big implications, and by comparing the sequences of children with related symptoms the disease causing mutations can be distinguished from natural variants.
In most cases knowing the cause does not lead to a cure, but Jane says the value of the diagnosis itself is life changing. “Having a medical label for your child’s problems helps families to access support and health services much earlier.”
A diagnosis also allows connections to be made with other children around the world. There is a Facebook group set up for children with Chrissy’s deletion where parents can check symptoms and offer advice. Jane missed out on such support when Chrissy was a child as her daughter was not diagnosed until she was 22. “It would have been such a relief to chat with other parents when Chrissy was little. Psychologically, if I had known what was wrong, I wouldn’t have felt like such a bad parent or devoted so much time and energy searching for cures”.
DNA sequencing gains its power from the volume of information produced. However, the same deluge of data creates new ethical dilemmas. The sequence of the child’s DNA not only reveals their developmental condition; it also provides information about their risk of suffering from other unrelated diseases. Some of these risks are well understood, but most are due to the subtle interplay of different genes combined with life experiences. For a few genetic vulnerabilities there are preventative measures which can be taken, but for most risk factors the benefit of finding out is not clear cut.
This leaves a heavy burden on the shoulders of the clinician. When they announce the diagnosis of the developmental disorder, should they also tell the parents that their child is likely to develop diabetes, breast cancer or Huntington’s disease? And that the parents may also share similar disease risks? There are no simple solutions, which is why the DDD project encompasses ethics research too.
The machine at the Sanger Institute finishes its run and
the children’s sequences are available for analysis. The next set of samples is
loaded and the machine continues, unaware of its impact, quietly generating
results that touch the lives of many.
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