Evaluation of a Strabismus Susceptibility Locus on Chromosome 7p in Japanese Pedigrees

Abstract

Abstract: : Background: Genetic background of strabismus has been suggested by the familial occurrence and the presence of large pedigrees with strabismus including both esotropia and exotropia. However, causative genes for strabismus have not yet been elucidated until now. As a first step towards the discovery of causative genes for strabismus, we searched for strabismus susceptibility loci in 30 Japanese pedigrees with either esotropia or exotropia (Genome–wide search for strabismus susceptibility loci. Acta Medica Okayama 2003;57:109–116). Although several loci were suggested, we could not find any loci with definitive linkage due to the small number of pedigrees. Our ongoing research is underway to include a larger number of pedigrees with strabismus. Concurrent with our study, a report from the United States (PNAS 2003;100:12283–12288) exhibited high LOD scores in the 7p22.1 region (maximum LOD score=4.51), suggesting causative genes located in this chromosomal locus. Purpose: We examined whether the 7p22.1 region reported in the United States is also a candidate locus in our Japanese pedigrees with strabismus. Methods: According to the method approved by the Ethical Committee of Okayama University Medical School, genomic DNA was extracted from blood samples obtained from strabismus patients and their family members. Using an ABI310 Genetic Analyzer^TM, genotypes were determined with microsatellite markers in the 7p22.1 region. Non–parametric linkage (NPL) scores were calculated using the genetic statistical analysis with a computer program (Genehunter^TM), and the values were compared with those reported for the American pedigrees. Results: Blood samples were collected from members of 39 pedigrees with strabismus: 24 pedigrees predominantly with exotropia and 15 pedigrees predominantly with esotropia. NPL scores (p values) were 0.44 (0.31) at D7S531, 0.50 (0.29) at D7S517, 1.71 (0.03) at D7S513, 1.24 (0.09) at D7S507, 0.82 (0.18) at D7S493, and 1.23 (0.42) at D7S516. Conclusions: Possible linkage of this chromosomal locus with strabismus was also exhibited in the Japanese pedigrees. Lower NPL scores in this study, compared with those in the American report, might be attributed to the small sample size.

Keywords: strabismus • gene mapping • linkage analysis