Gene Implicated in Rare Form of Hereditary Anemia

Researchers studying the genetic basis for a rare type of hereditary anemia have identified a 28-exon gene on chromosome 15 that codes for a glycosylated protein, which may be involved in nuclear envelope integrity and possibly related to microtubule attachments. Their findings were reported in the December 2001 issue of the American Journal for Human Genetics.

Investigators from Tel Aviv University (Israel;) and the Weizmann Institute of Science (Rehovot, Israel) studied a cluster of 45 highly inbred Israeli Bedouin with congenital dyserythropoietic anemia-1 (CDA-1). Working with this population enabled the mapping of the CDAN1 disease gene to a 2-Mb interval, now refined to 1.2 Mb containing 15 candidate genes on chromosome 15.

CDA-1 is characterized by a medium-to-high deficiency in blood production, and in critical cases patients must receive blood transfusions throughout their lifetime. It is a rare disease, but the largest vulnerable group is the Bedouin population living in the Negev Desert, where marriage among relatives is common.

The researchers characterized and excluded 13 of the candidate genes before identifying the CDAN1 gene through 12 different mutations in nine families with CDAI. This 28-exon gene was reconstructed on the basis of gene prediction and homology searches. It encodes codanin-1, a putative o-glycosylated protein of 1,226 amino acids, with no obvious transmembrane domains. Codanin-1 has a 150-residue amino-terminal domain with sequence similarity to collagens and two shorter segments that show weak similarities to the microtubule-associated proteins, MAP1B (neuraxin) and synapsin. These findings, and the cellular phenotype, suggest that codanin-1 may be involved in nuclear envelope integrity, conceivably related to microtubule attachments.





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Tel Aviv University
Weizmann Institute of Science