Gene responsible for anemia (type CDA-1) discovered

A rare type of the disease found mainly in Bedouins may provide insight into anemia

A combined effort between scientists at Schneider Children’s Medical Center of Israel, Tel Aviv University, and the Weizmann Institute of Science has led to the discovery of a gene responsible for a type of anemia primarily found in a number of Bedouin families, called congenital dyserythropoietic anemia-1 (CDA-1). The findings, published in the December issue of The American Journal for Human Genetics, could lead to effective detection and eventually treatment of the disease. In addition, understanding the role of this gene’s protein product in the body could provide important clues to other types of anemia, as well as to the general mechanisms of blood cell formation.
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 present worldwide, but the largest vulnerable group is the Negev Desert’s Bedouin population, where marriage among relatives is common. The high disease prevalence in this Israeli population was crucial to the identification of the CDA-1 gene.

The study group included 45 Bedouins treated by Dr. Hannah Shalev at the Soroka Medical Center in Beer Sheva. Initially, a team headed by Dr. Hannah Tamary, who works both at Schneider and the Felsenstein Medical Research Center in Tel Aviv University’s Faculty of Medicine, narrowed down the search for the gene to a region on a specific chromosome (chromosome15) . To uncover the gene in that region, they then turned to Profs. Doron Lancet and Jacques S. Beckmann of the Crown Human Genome Center at the Weizmann Institute’s Molecular Genetics Department. Both teams, after four years of intensive research, discovered and characterized the previously unknown gene, named CDAN1.

Dr. Orly Degani, who works with Tamary, says: “The genomic region within which the gene for CDA-1 was hiding was unusually complex. In some of the patients, a complete DNA segment was missing, but it turned out that this did not cause the disease.”

“We thought fifteen genes were good candidates,” says Dr. Nili Avidan, who works with Beckmann and Lancet. “We began checking them one after the other, from short, defined genes to long, putative ones. This gene was one before the last.”

The researchers observed that mutations in this specific gene correlate with the disease. These mutations modify a previously unknown protein, which they named Codanin-1. The protein, they suspect, is present in the nuclear envelope of bone marrow cells, which divide and give rise to red blood cells. Studies of this protein, which may become an important pharmaceutical target similar to erythropoietin (EPO) may yield a better understanding of blood cell maturation and anemia and eventually lead to an effective remedy for CDA-1.

Prof Lancet’s research is supported by Wolfson Family Charitable Trust, Crown Human Genome Center, Henri and Francoise Glasberg Foundation, Alfried Krupp von Bohlen und Halbach Foundation, Kalman & Ida Wolens Foundation, the Avraham and Yehudit (Judy) Goldwasser Fund, Ms. Emilia Mosseri, London, Mr. James Klutznick, Chicago, IL and the Jean-Jacques Brunschwig Memorial Fund.

Prof. Lancet is the incumbent of the Ralph and Lois Silver Professorial Chair in Human Genomics.