Figure 1

USH1 gene mutations in Quebec and haplotype analysis of the USH1C founder mutation c.216G>A. (a) Distribution and proportion of USH1 gene mutations in Quebec. Numbers designate patients, colors indicate different USH1 genes. Superscript symbols indicate different mutations that are listed beside the diagram. Note that c.216G>A is present all along the St Lawrence river, suggesting that it was present from the beginning of colonization by French settlers. In sum, USH1C mutations account for 60% of USH1 cases investigated in this study. In the case of patient 1881, no mutation could be identified in any of the known USH1 genes. See Additional data file 4 for the precise origin of each patient. (b) Genomic structure of the USH1C gene and haplotype bearing the c.216G>A mutation in different patients. Constitutive exons are given in black, alternatively spliced exons in grey. Mutations identified in this study are given above. Asterisks indicate novel mutations. Designations of intragenic SNPs and polymorphic microsatellite repeat markers are given below (SNPs in bold are referred to in Figure 2). The corresponding UCSC map positions are indicated below the scheme of the USH1C gene. 'VNTR' designates the 45 bp variable number of tandem repeat polymorphism in intron 5, which is in complete linkage disequilibrium with the c.216G>A mutation. Presence of the 9VNTR(t,t) allele is indicated by '9'. Alleles of microsatellite markers are represented by numbers indicating different repeat lengths. Slashes indicate that marker alleles could not be assigned definitively to a haplotype. For biallelic SNPs, the respective nucleotide is given (according to the genomic USH1C sequence in 5'-3' orientation). Haplotype IDs and respective patients are given in the left column. Haplotypes associated with c.216G>A are in red. For patients who are compound heterozygous for c.216G>A and another mutation, only the c.216G>A-associated haplotype is shown. Recombination events are indicated by grey background. Acadian: for comparison of the c.216G>A-associated haplotype ('Acadian allele') with haplotypes in our sample, we have genotyped the family of a previously described patient with homozygosity for c.216G>A (see Additional data file 1a). As there is a recombination event in this patient for marker D11S1349, both alleles are shown. 1-4: haplotypes from patients 1172, 367, 554, and 1116 who are homozygous for c.216G>A. In the case of a recombination event, only the corresponding allele is shown. 5-7: c.216G>A-associated haplotypes from compound heterozygous patients. 8: c.216G>A-associated haplotype from healthy carrier (Q14).