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Blood, Vol. 91 No. 8 (April 15), 1998:
pp. 2643-2644
COMMENTARY
An Electronic Database of Human Hemoglobin Variants on the World Wide
Web
By
David H.K. Chui,
Ross Hardison,
Cathy Riemer,
Webb Miller,
M.F.H. Carver,
T.P. Molchanova,
G.D. Efremov, and
Titus H.J. Huisman
From the Provincial Hemoglobinopathy DNA Diagnostic Laboratory and
Department of Pathology, McMaster University, Hamilton, Ontario,
Canada; the Department of Biochemistry and Molecular Biology and the
Department of Computer Science and Engineering, and the Center for Gene
Regulation, The Pennsylvania State University, University Park, PA; the
Research and Education Building, Medical College of Georgia, Augusta,
GA; The Sickle Cell Anemia Foundation, Augusta, GA; and the Macedonian
Academy of Sciences and Arts, Research Center for Genetic Engineering
and Technology, Skopje, Republic of Macedonia.
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ARTICLE |
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  °-thalassemia), severe anemia requiring life-long
transfusions and iron chelation ( -thalassemia major), risk of death
during infancy and vaso-occlusive 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 -, -,  -, and  -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 Contents, which is hyperlinked to a separate table for
each class of globin variants and to the full entry for each
variant. Figure 1 shows the entry for Hb
C-Harlem, including representative literature references.
An additional and useful feature of this on-line version of the
Syllabus is that it allows simple queries. By using the
"Search" link, users can search for matches between a word or
phrase they enter and relevant information in all or selected fields of
the database. For example, searching for "beta6" will return all
hemoglobin entries that mention an alteration at position six of the
-globin chain from all sections of the Syllabus. Some
limited flexibility in formulating the query is provided via optional
checkboxes, and future developments, such as the use of a table of
synonyms, will increase the efficiency of these searches.
This electronic format has advantages that complement the printed
material. The World Wide Web provides easy access to users around the
world, thereby increasing the utility of the compiled information and
facilitating future collaborations. The database can be
updated frequently to include information on new discoveries. It also
allows queries that can bring out relationships and information that
are difficult to find by reading the syllabus with its voluminous data.
However, the converse is also true; reading and analysis by humans will
bring out relationships that cannot be duplicated by electronic query
engines. Thus, the printed book and electronic database provide
complementary paths to locate the information needed for either
clinical care or research purposes.
Work is in progress to convert the Syllabus on the thalassemic
and related mutations, which describes more than 315 mutations, to an
electronic form to make it publicly accessible in the near future.
Attempts will be made to improve these databases to handle complex
queries as required by many biomedical investigators. These
globin-gene related databases will be partners to the worldwide alliance6 of "locusspecific databases"
administered by the Human Genome Organization.
In the Globin Gene Server, we have applied computational information
technology to provide multiple alignments of globin gene DNA sequences
from different species and to establish databases on results of
laboratory experimentation and manipulation of the globin
genes.7 The addition of the human natural mutations and
their pathophysiology databases is a logical extension of our efforts
to integrate diverse information to better understand the globin gene
structure, regulation, expression, and function.
In December 1997, 15 leading clinical investigators from the United
States, Canada, France, Hong Kong, and the United Kingdom met in San
Diego to discuss the possible establishment of a database recording
individuals' globin-genotypes, hematological and clinical findings,
pedigrees, and therapeutic responses. If carried out, the depository
will be constructed in such a way that individual confidentiality is
respected and protected securely. A panel of editors will be assembled
to ensure of the accuracy of the entries. This collation of findings
from around the globe will be helpful for laboratory diagnosis, genetic
counseling, and patient care. It can be useful to plan for treatment
strategies, provide insight into the correlation between genotypes and
phenotypes in different populations, and help to identify and
investigate novel clinical findings of biological importance. When
successful, it can also become a useful prototype for the development
of databases for other genetic and nonhereditary diseases.
Bioinformatics is becoming fully integrated into basic research in
biology and medicine. The development of databases of clinical relevance should make bioinformatics increasingly important as an aid
to the practice of medicine.
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FOOTNOTES |
Submitted October 27, 1997;
accepted January 8, 1998.
Supported by Public Health Services Grants No. LM05773, LM05110, and
DK27635 and by The Sickle Cell Anemia Foundation (Augusta, GA).
Address reprint requests to Ross Hardison, PhD, Department
of Biochemistry and Molecular Biology, The Pennsylvania State
University, 206 Althouse Laboratory, University Park, PA 16802; e-mail:
rch8{at}psu.edu.
The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" is accordance with 18 U.S.C. section 1734 solely to indicate this fact.
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REFERENCES |
1.
Pauling L,
Itano H,
Singer SJ,
Wells IC:
Sickle cell anemia: A molecular disease.
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2. Bunn HF, Forget BG: Hemoglobin: Molecular, Genetic and Clinical
Aspects. Philadelphia, PA, Saunders, 1986
3. Beutler E, Lichtman MA, Coller DS, Kipps TJ: Williams Hematology.
New York, NY, McGraw-Hill, 1995
4. Huisman THJ, Carver MFH, Efremov GD: A Syllabus of Human
Hemoglobin Variants (1996). Augusta, GA, The Sickle Cell Anemia
Foundation, 1996
5. Huisman THJ, Carver MFH, Baysal E: A Syllabus of Thalassemia
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Hardison R,
Riemer C,
Chui DHK,
Huisman THJ,
Miller W:
Electronic access to sequence alignments, experimental results and human mutations as an aid to studying globin gene regulation.
Genomics
47:429,
1998[Medline]
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