20 June 2016
ByAppeared in BioNews 856
BBC Radio 4, Monday 23 May 2016
Presented by Winifred Robinson
Thirty years ago, Professor Sarah Bundey and her colleagues studied 5000 pregnancies at the Queen Elizabeth Hospital in Birmingham. They recorded data on the social aspects, the ethnic origins and family history, including degrees of consanguinity.
The initial results from the Birmingham Births, or 'BB', study were striking. They showed that families of Pakistani origin – often from the Mirpur district – who tended to marry first cousins, had significantly higher neonatal mortality and also more children who developed autosomal recessive (AR) genetic conditions, which were often severe.
This suggested that frequent consanguinity within affected families over several generations had raised the prevalence of AR mutations, and that first-cousin marriages within such communities had led to more children with a double dose of the abnormal genes (who would therefore develop the conditions) being born. Alas, some politicians seized on this data to berate Pakistani families and complain that their propensity to first-cousin marriage had placed an excessive burden on NHS facilities.
Bundey was later awarded a personal chair in the clinical genetic infant development unit at Birmingham University. With her colleagues she planned to work towards designing genetic management for Pakistani families at higher risk, with care packages offered sensitively within the NHS, taking note of religious and other cultural practices.
A suggestion of the team (which may not in fact have worked) was to encourage marriages between less closely related family members rather than between first-degree cousins, in the hope that the AR risk would be lowered. Sadly, Sarah died in 1998 and was unable to pursue this project.
Bundey would have been pleased to hear of the Born in Bradford study, which began in 2007 and recorded data prospectively from 12,000 mothers, 4000 fathers and their 14,000 children born in Bradford General Hospital. The data included medical, psychological and psychometric tests as well as DNA stored for studies on genetic markers in key families.
Winifred Robinson's report on the Born in Bradford study for the BBC partially focused on a Muslim family in which two children had been affected by I-cell disease, a fatal AR disorder. Both children had died and their mum suspected that her third child was also affected (as did the consultant paediatrician).
However, that paediatrician did not wish to 'communicate too much to the mother' to 'allow time for the journey of mum and baby to get to know each other'. My quibble here is that when parents know of an increased genetic risk (which is one in four for AR conditions like I-cell disease) and have received genetic counselling about the implications for further pregnancies, it is surely better for the doctor to be open and honest, rather than to avoid discussion of the likely scenario. Or he could have asked the parents in advance what they wished him to share for this part of their management.
The programme then moved on to look at other conditions, particularly type 2 diabetes, resulting from the present epidemic of obesity, unhealthy diets and lack of exercise. We heard a dietary history being taken from an Asian woman who had been drinking around six litres of Coca-Cola daily (and whose diabetes unsurprisingly improved when she gave up that drinking habit).
We also learnt that diabetes was five times more frequent in people of South Asian origin, which led on to the DNA data from the Born in Bradford study. This work has highlighted a paradox which challenges what had become something of a dogma in genetics – the idea that, as genes in different species show considerable homology, they must be similar at the molecular level.
The reasoning continues by suggesting that the most homologous genes across species are the most important 'housekeeping' genes of the animal kingdom. The dogma has led to genes being sequenced in one animal species in the belief that they would be identical in others. But an incidental finding of the Born in Bradford study suggests that this may be a mistaken assumption.
Furthermore, in the study some people who inherited the same mutant genes from both parents – who were therefore homozygous – did not develop the lethal form of the attendant disease, despite the same genes always resulting in lethality in other species. Similarly, in the Born in Bradford study women who were homozygous for mutations which in other species cause infertility were definitely fertile. This must mean that other mechanisms, unconnected to those mutant genes, can compensate for the missing function. Again, this challenges other assumptions that were made previously about genetics.But for years both Bundey and I recognised that today's well-established principles are often disproved tomorrow. Just as the Bradford study superseded the Birmingham study and added new ideas and concepts, there may be soon a 'Born in Britain' study which explores and explains facets of our genetic and ethnic diversity even further. These findings, whatever they may be, would have surely delighted and stimulated Professor Bundey's great intellect, had she lived to consider them.