High frequencies of some rare inherited recessive disorders can be found in the Saguenay region of Quebec, Canada. Four disorders have a carrier frequency of about 0.04 (in the range 0.035-0.05): pseudovitamin D-dependent rickets, hereditary tyrosinemia type 1, Charlevoix-Saguenay spastic ataxia, and sensorimotor polyneuropathy with or without agenesis of the corpus callosum. Molecular data suggest that only 1 mutation has been introduced into the population since its founding in the 17th century. The carrier frequencies are much higher than one would expect under a theoretical model that includes variance in family size and population growth (Thompson and Neel 1978). I present a methodology called allele dropping to test the hypothesis that only 1 founder introduced a given mutation. This study is based on 891 ascending genealogies and enables one to measure the extent of allele frequency changes resulting from the demographic history of the population. Two scenarios are tested: neutral and lethal alleles. Lethality has a minor effect because the alleles never reach a frequency high enough for selection to be strong. Twenty-five founders have a probability greater than 1% that a lethal mutation they introduced into the population will reach a carrier frequency between 0.035 and 0.05 in the contemporary population. Moreover, 2 founders have a probability greater than 20% that a lethal allele they introduced into the population will reach this target frequency. Therefore the simplest hypothesis that 1 founder introduced 1 disorder into the population is consistent.
"One Founder/One Gene Hypothesis in a New Expanding Population: Saguenay (Quebec, Canada),"
1, Article 8.
Available at: https://digitalcommons.wayne.edu/humbiol/vol71/iss1/8