Population genetics of vitamin D‐dependent rickets in northeastern Quebec

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Abstract
Vitamin D-dependent rickets (VDD1) is an autosomal recessive disorder that was recognized in Saguenay-Lac-St-Jean (SLSJ) in 1970. The great majority of the VDDl cases reportedin the French Canadian population of Quebec originated from SLSJ, Charlevoix, and the Haute CGte Nord, all regions located in northeastern Quebec. The prevalence a t birth in SLSJ was estimated a t 112916 live borns, and the carrier rate was estimated a t 1/27 inhabitants in the SLSJ region. The mean coefficient of inbreeding was not elevated in the VDDlgroup of SLSJ compared with three matched control groups. The mean coefficient of kinshipwas 2.5 times higher in the VDDl group than in the control groups. In the SLSJ region, the places of origin of the VDDl children and their children did not show a clustered non-uniform distribution. Endogamy was not found to be higher in the VDDl group than in controlgroups. The genealogical reconstruction showed all the obligate carriers of the VDDl gene, but one, to be related to a small set of founders who settled in New France in the 17thcentury. All these results, as well as a strong linkage disequilibrium between RFLPs located on the long arm of chromosome 12 and the VDDl locus, support the hypothesis of a founder effect for VDDl. They also suggest that a unique mutation accounts for most, if not all, of the cases known in northeastern Quebec.