Diamond Blackfan anemia (DBA) is a rare congenital pure red cell aplasia characterized by severe normochromic, macrocytic anemia that usually presents early in infancy. Although most reported cases are sporadic there is evidence of inheritance, both dominant and recessive in about 12 - 25 percent of cases. The goal of this proposal is to isolate the dominant DBA gene. Because of recent evidence of genetic linkage to chromosome 19q we will first use DNA that we have collected from 5 Polish and 7 American DBA families to test this association. If this report cannot be confirmed we will perform linkage analysis on the whole genome. If evidence for linkage is found, either to chromosome 19q or to another region of the genome, we will use further polymorphic markers to fine map the region. This map will be used for a positional candidate gene approach to determine whether any likely genes are present within the mapped domain(s). Finally, we plan to examine candidate genes for mutations in affected but not unaffected family members using Southern blotting, single stranded conformation polymorphism (SSCP), and sequencing of the putative dDBA genes.
| Gazda, H; Lipton, J M; Willig, T N et al. (2001) Evidence for linkage of familial Diamond-Blackfan anemia to chromosome 8p23.3-p22 and for non-19q non-8p disease. Blood 97:2145-50 |
