The clinical need

Patient participation is crucial to our work, which is governed by patient need. Some of the important demographic factors driving our research are listed below.

High rates of consanguineous marriage in Bradford and West Yorkshire

Bradford has a population of 470,000, with 6,000 live births in 2006 (1). Although only 18% of the Bradford population is of south Asian origin, 50% of births are to south Asian families (cf. 31% in 1996). In 1988, 70% of Bradford Pakistani couples were consanguineous (2). Data from the first 1,000 women recruited into the Born in Bradford birth cohort study (3) indicate that this figure remains unchanged.

Increased recessive inherited disease due to consanguinity

Autosomal recessive (AR) diseases occur when a child inherits two copies of a gene, one from each parent, both genes carrying a harmful mutation. The chance of having a child with an AR condition is increased if both parents are blood relatives. Consequently, in communities in which consanguineous marriage is common, there is a significant increase in the prevalance of AR disease (4). A 1993 study from Birmingham recorded a 16-fold increase in AR diseases in the offspring of consanguineous Pakistani couples, compared to non-consanguineous couples (5).

Increased mortality and morbidity in West Yorkshire Pakistani children

Babies born to Pakistani women in Bradford are twice as likely to die in their first year of life than babies born to white mothers. In 2006, an Infant Mortality Commission (IMC) concluded that AR disorders were a significant factor explaining this differential (1, 6). Additionally, a number of studies have indicated that childhood morbidity due to AR disease is greater in West Yorkshire than in other regions of the UK (7-10). As an example, Bradford was the highest reporting centre to a national study of paediatric neurodegenerative conditions (11).

Targetting molecular genetic testing

It is now possible to identify AR genes using small numbers of families. As examples, driven by the needs of local patients our own molecular research has resulted in both gene identification (12-14) and the subsequent provision of gene testing in the Yorkshire Regional DNA Laboratory (15) for Aicardi-Goutières syndrome and PMS2-associated cancer.

1. Bradford District Infant Mortality Commission:
http://www.bdimc.bradford.nhs.uk/

2. Darr A, Modell B. The frequency of consanguineous marriage among British Pakistanis. J Med Genet 1988 25:186-190

3. Born in Bradford birth cohort study:
http://www.borninbradford.nhs.uk

4. Bittles AH, Neel JV. The costs of human inbreeding and their implications for variations at the DNA level. Nat Genet 1994 8:117-121

5. Bundey S, Alam H. A five-year prospective study of the health of children in different ethnic groups, with particular reference to the effect of inbreeding. Eur J Hum Genet 1993 1:206-219

6. 2006 Annual Report of the Chief Medical Officer (page 63):
http://www.dh.gov.uk

7. Sinha G et al. Prevalence and type of cerebral palsy in a British ethnic community: the role of consanguinity. Dev Med Child Neurol 1997 39:259-262

8. Corry PC. Intellectual disability and cerebral palsy in a UK community. Community Genet 2002 5:201-204

9. Schwarz K et al. Survey of school children with visual impairment in Bradford. Eye 2002 16:530-534

10. Yoong SY et al. Families affected by deafness: hospital services uptake in a multiethnic population. Archives Dis Child 2005 90:454-459

11. Devereux G et al. Variations in neurodegenerative disease across the UK: findings from the national study of Progressive Intellectual and Neurological Deterioration (PIND). Archives Dis Child 2004 89:8-12

12. Crow YJ et al. Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutières syndrome and mimic congenital viral brain infection. Nat Genet 2006 38:910-916

13. Crow YJ et al. Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus. Nat Genet 2006 38:917-920

14. De Vos M et al. Novel PMS2 psuedogenes can conceal recessive mutations causing a distinctive childhood cancer syndrome. Am J Hum Genet 2004 74:954-964

15. Yorkshire Regional Genetics Service DNA Laboratory:
http://www.leedsdna.info