Autosomal recessive disorders in Saguenay-Lac-St-Jean, Quebec: study of kinship.

Saguenay-Lac-St-Jean is a geographically isolated region of northeastern Quebec in which several autosomal recessive disorders have a high incidence. The kinship coefficients of all possible pairs of 567 probands were calculated and compared with those of 1701 matched control individuals. The mean kinship coefficient of the group containing all 567 probands was 5.57 times higher than that of the control group (0.000981 versus 0.000176). Overall, 45.5% of the probands were third-degree cousins, compared with 32.9% of the control group. However, in each disorder only a few probands were traced back to the most represented founder couple in Saguenay-Lac-St-Jean. Molecular data added a new dimension to the concept of kinship by showing that at least in the study area, closely related individuals do not necessarily carry identical mutations, which, in turn, may have a great impact on carrier screening. Our results strongly suggest that the high incidence of autosomal recessive disorders in Saguenay-Lac-St-Jean is the result of a founder effect.