VERWANT: improving risk assessment in consanguineous couples by means of SNP analysis
Background
Children of consanguineous couples are at increased risk of morbidity and early mortality. The level of risk depends on the degree of relationship of their parents. For instance for children of first cousins the risk of congenital/genetic disorders and of early mortality is 2-3% and about 4%, respectively, above the level for children of unrelated partners. The excess risk is mainly caused by autosomal recessive disorders, most of which have not manifested themselves in the wider family yet.It is estimated that one in every 12 children world-wide has consanguineous parents. The prevalence of consanguinity is 20 or more percent in one-sixth of the world population. In the Netherlands consanguinity is found especially in migrant populations, for example in Turkish and Moroccan immigrants and their descendants. It is understood that 20-25% of the marriages in these communities are consanguineous matings.
If one compares the 2-4% excess risk in offspring of first cousins with the 25% risk for children of parents who are carriers for an autosomal recessive disease, one has to conclude that of all first cousin couples a minority is at significant high risk (25% or more), while the majority has no or a very limited excess risk. The ambition of this research is to develop and test a method which can distinguish prospectively among all consanguineous couples the ones that are at high risk and the ones at low risk.
The excess risk of autosomal recessive disease in the offspring of consanguineous couples is
conditional on: 1) the presence of identical alleles in both parents, descending from the common ancestor(s); 2) the presence of pathological mutations in the ancestral alleles. The more DNA identical by descent is shared by parents, the higher the risk of excess morbidity and mortality in their children. The proportion of shared DNA can be assessed by genome-wide single nucleotide polymorphism (SNP) analysis.