SCOOTER82a_Livingstone_Frequencies of Hemoglobin Variants ...

The frequencies and results compiled in the
table were determined by the entire range of
techniques developed in the last fifty years, from
the crudest sickle cell test or microscopic determination
of microcytemia to the DNA sequencing
of the entire a or (3 chain. This leads to difficulties
in recording such disparate data in a
single format and in calculating "gene" frequencies.
Of course, what entity's frequency can be
calculated is dependent on the level of measurement.
For example, at the most inclusive or
inexact level, thalassemia can be detected by
the osmotic resistance of the red cells and one
can calculate the frequency of the "thalassemia"
gene. But then measuring the level of A2 hemoglobin
can distinguish (3-thalassemia from a-thalassemia.
Thus, whatever gene frequencies are
calculated in that column of the table are dependen
on the types of tests used to obtain the data
recorded in the Results column.
The Reference, Population, Place, and Number
Tested columns are self-explanatory. In
many cases where there was a clinical condition
or other characteristic of the population that
may have an effect on the results, this is
recorded in parentheses in the Population column.
Sex is only noted for the G6PD variants or
deficiency because there is very little evidence
of a marked effect of sex on the hemoglobin or
thalassemia frequencies.
The Systems column was added in order to
facilitate the selection of the frequencies of
interest. In addition, it was hoped that describing
the system would make it possible to use more
EXPLANATION OF THE DATA TABLE
simplified notations in the Results column.
Nevertheless, to reduce the many kinds of data
to a few lines in the Results column proved to
be the most difficult task. Alas, it is also still the
most difficult part of the table to comprehend.
To summarize the data, a great number of
abbreviations have been used. First, the Greek
letters are not generally available on the Michigan
Terminal System, so that for the a, (3, 'Y, and
ochains of hemoglobin, the letters a, b, g, and d
are used in both the Results and Gene Frequency
columns. The recording of hemoglobin
variants follows the idiosyncrasies of the development
of our knowledge of these variants. At
first each new variant was assigned a new letter,
so that today there are hemoglobins C, D, E, and
on upto P. The pace of discovery then rendered
this system of nomenclature obsolete or inadequate.
Prior to that, sickle cell hemoglobin had
been assigned the letter S, although B was first
used for it and this resulted in no hemoglobin
being assigned to B. F was assigned to fetal
hemoglobin, which had been known for a long
time, but since fetal hemoglobin contains 'Y and
not (3 chains, fetal hemoglobin variants are not
alleles of the adult hemoglobins. Hemoglobin
variants then began to be identified by geographical
location although some were more
specific than others; thus there is hemoglobin
Mexico, hemoglobin Hammersmith (a suburb of
London), hemoglobin Altgeld Gardens (an apartment
complex in Chicago), and everything in
between. However, the letter designations were
retained to indicate the electrophoretic behavior
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of the hemoglobin; for example, hemoglobin
GAccra indicates a mobility like hemoglobin S
and G, a charge slower than hemoglobin A, but
with no sickling associated with it. Occasionally,
the exact amino acid change is not known but
the chain the mutation is on is known so that D(3
is a D variant on the (3 chain or Ga is known for
the a chain. On the table these would be Db or
Ga.
The variants of adult hemoglobin, or mutations
of the a and (3 chains, have been recorded
as well as they are known with no prefixing identification.
Thus, asAD, ADb, or ADPunjab, when
heterozygous, for example, or as Avariant when
the abnormal variant has not been identified.
Other genotypes are shown as D, DD, DbTh,
according to whether the investigator has
attempted to distinguish the single hemoglobin
pattern as due to homozygosity or simultaneous
heterozygosity for an allelic thalassemia gene.
For each population, the name of the variant is
first spelled out but then abbreviations have
been used, for example, Lepore then Lep.
On the other hand, variants of A 2 or fetal
hemoglobin are identified as such, for example,
A2 Flatbush or FSardinia. These variants are
assumed to be heterozygous, but when they
have been distinguished, (het) and (hom) are
appended. Many populations have been tested
for elevations of either A 2 or fetal hemoglobin to
detect (3-thalassemia or a condition called the
hereditary persistence of fetal hemoglobin
(HPFH). These are indicated by A2, F, or HPFH
although the latter appears to be a single gene