Genome-Wide Scanning For A Nonsyndromic Autosomal Dominant Postaxial Polydactyly In A Six-Generation Family

Genome-Wide Scanning for A Nonsyndromic Autosomal Dominant Postaxial Polydactyly in A Six-Generation Family: A New LocusLimb malformations are most common in human congenital defects. Polydactyly is the most frequently observed congenital limb malformation. These malformations can occur isolately, in combination with other hand and/or foot anomalies, or as a part of a syndrome. Because limb development encapsulates all the fundamental processes that contribute to building an embryo and is a tour de force in pattern formation, genetic mechanisms involved in human polydactyly will help us to reveal the secrets of human development. In recent years, more and more researchers focus on this field.Family investigation, clinical diagnosis and collection of blood samplesFamily investigation demonstrated that postaxial polydactyly in the family is inherited in a classic autosomal dominant mode and passed along in six generations. Clinical diagnosis was made by the pediatricians of Peking Union Medical College Hospital and it showed that this disorder is a nonsyndromic postaxial polydactyly. Blood samples from 32 members in four generations we have collected. 16 of them were affected, 16 were normal phenotypically including an obligate carrier.Exclusive mapping in this family with markers on or near the loci that have been reported before There were four polydactyly-related loci that have been reported on 2q31, 7p13, 7q36 and 13q21-q32 respectively. Specific markers on or near these four loci were choosed and results of linkage analysis showed there was no linkage with these loci in this family. These were confirmed by genome wide scanning.Genome wide scanning in this family After the excluding the previously identified loci , genome wide scanning was carried out. 416 polymorphism markers on 22 autosomal chromosome were used and 259 of them were amplified successfully. The average genetic interval between markers was 20 cM. The results of linkage analysis revealed that in a 40cM region between markers D19-4 and D19-8, 5 adjacent markers had Lods scores more than 1, suggesting that a new locus for postaxial polydactyly might be located on chromosome 19.Fine mapping of a new locus in this postaxial polydactyly family on chromosome...