Objective To identify the genetic pattern and locate the genes related to late-onset congenital cataract FVB mouse. Methods First, the phenotype of cataract mice was identified using histopathological slides and the genetic pattern of congenital cataract phenotype was identified by constructing pedigrees. Second, the linked chromosome was located by whole-genome SNP scanning based on multiplex PCR targeted sequencing. Finally, screening of candidate mutant genes was performed by sequencing the whole exome of two cataract mice, one wild-type mouse, and four F2 cataract mice with a mixed genome. Results The result of whole-genome scanning of 100 F2 mice showed the highest linkage between rs4228772 SNP on chromosome 11 and the cataract phenotype, with a 82. 11% homozygous rate. The result of whole-exome sequencing further demonstrated three genes that had spontaneously mutated on chromosome 11:Sfi1,Obscn,andPtrh2. Conclusions The combination of whole-genome SNP scanning and whole-exome sequencing strategies revealed that congenital late-onset cataract was caused by mutated genes on chromosome 11 and inherited as a dominant trait. This method may also be applied to the study of gene function in other model mammals with a clear genetic background.