An electronic database of human hemoglobin variants on the World Wide Web.

HUMAN HEMOGLOBINS and their variants have been the subjects for fruitful clinical and basic research for many years. The knowledge derived from these studies is essential in understanding the relationship between hemoglobin structures and functions. The report on the seminal study of sickle hemoglobin by Pauling et al1 in 1949 provided the first example of molecular disease. With the advances in molecular biology during the past decades, the study of human globin genes and their mutations continues to lead the way in understanding molecular genetics and its clinical relevance. Presently, there are more than 1,000 known mutations involving the human globin genes. Many of these mutations are associated with clinically significant phenotypes. They include in utero fetal death (homozygous a°-thalassemia), severe anemia requiring life-long transfusions and iron chelation (b-thalassemia major), risk of death during infancy and vasoocclusive events resulting in multiple organ damage in adults (sickling disorders), hemolytic anemia (unstable hemoglobin variants), cyanosis (methemoglobins), and erythrocytosis (high oxygen affinity hemoglobin variants). New mutations of the globin genes are still being discovered today. The literature on the human hemoglobin variants and globin gene mutations is vast. Some of this information has been tabulated in monographs2 and in textbooks of hematology.3 Updated listings of known variants are published periodically in the journal Hemoglobin. More recently, two comprehensive syllabi were published, one on human hemoglobin variants4 and the other on the thalassemic and related mutations.5 We have recently made available in the World Wide Web the electronic version of the Syllabus of Human Hemoglobin Variants, describing 693 variants. They are arranged according to those resulting from single base changes in the a-, b-, g-, and d-globin genes; those with more than one amino acid substitution; those with longer or shorter polypeptide chains; and those producing hybrid globin chains. This Syllabus is accessible at the Globin Gene Server (http://globin.cse.psu.edu). Users can follow the ‘‘Browse’’ link to the Table of