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ABSTRACT

INCIDENCE AND AGE RELATED FREQUENCIES OF
HEMOGLOBIN S IN SELECTED RANDOM AND
NONRANDOM POPULATIONS

By
Frankie J. Brown

Blood samples from 4208 black Americans were ana-
lyzed for the presence of hemoglobin S by use of cellulose
acetate electrophoresis and by solubility determinations
in a 2.3 molar phosphate buffer solution. The individuals
tested were derived from five sample groupings, one of
which was randomly selected from the Lansing, Michigan
black population, two which represented the results of non-
random screening programs from the same general area, one
from a college testing program, and one from a state insti-
tution for the mentally retarded.

The gene frequency for the hemoglobin S allele in
the random sample was found to be 0.043. When compared to
this value, no significant frequency differences for the
allele were found in the nonrandom populations. (Variation

0.031 to 0.047.)

Frankie J. Brown

Comparisons of the observed and expected genotypic
frequencies for the AA, AS, AC, SS, CC and SC genotypes
failed to produce any significant differences in any of
the samples studied.

The age related frequencies for hemoglobin S car-
riers were calculated for four samples (the random sample
and three of the nonrandom groups). Results of these cal-
culations showed no significant differences in the percent
of AS individuals with age. Frequency fluctuations with
age did occur, however, as well as fluctuations in the mean
values for the percent of red cell hemoglobin S. These

fluctuations were not statistically significant.

INCIDENCE AND AGE RELATED FREQUENCIES OF
HEMOGLOBIN S IN SELECTED RANDOM AND

NONRANDOM POPULATIONS

by
'43 [\

‘ 3-, "x -"
Frankie J1 Brown

A THESIS

Submitted to
Michigan State University
in partial fulfillment of the requirements
for the degree of

MASTER OF SCIENCE
Department of Zoology

1973

To C.B. and Chuckie
and my parents

ii

ACKNOWLEDGMENTS

I wish to express my sincere appreciation to Dr.

J. V. Higgins, my major professor, for his guidance during
the course of this study.

I also wish to thank Drs. Herman Slatis, Hiram
Kitchen, and John R. Shaver for serving on my committee and
providing constructive criticisms.

I am especially indebted to Astrid Mack for his con«
tinual cooperation during the course of our joint efforts
in producing this study and the larger Lansing survey. With-
out his consistent collaboration this work would have been
a difficult if not an impossible task. Special thanks also
goes to Dr. Ajovi Scott-Emuakpor for his invaluable help
during the initial stages of the project.

For their friendship and moral support, I wish to
thank the following colleagues in the genetics lab: Lou
Betty Richardson, Carola Wilson, Gary Marsiglia, Bob Pandolfi,
Sally Cullen, Mike Abruzzo and Habib Fakhrai. Additionally,
for their technical assistance I wish to thank Al Davis,
Jackie Roberson and Beverly Ray.

Most of all, I shall be forever grateful to my hus-
band C.B. and son Chuckie for their understanding, patience
and support during every phase of my graduate program.

iii

This work was supported by grants from the Center
for Urban Affairs, Michigan State University and the Lansing

City Demonstration Agency (Model Cities).

iv

TABLE OF CONTENTS

Page
LIST OF TABLES . . . . . . . . . . . . . . . . . . . vi
LIST OF FIGURES . . . . . . . . . . . . . . . . . . vii
INTRODUCTION . . . . . . . . . . . . . . . . . . . . 1
LITERATURE REVIEW . . . . . . . . . . . . . . . . . 3
MATERIALS AND METHODS . . . . . . . . . . . . . . . 23
RESULTS . . . . . . . . . . . . . . . . . . . . . . 28
DISCUSSION . . . . . . . . . . . . . . . . . . . . . 46
CONCLUSIONS . . . . . . . . . . . . . . . . . . . . 55
BIBLIOGRAPHY . . . . . . . . . . . . . . . . . . . . 53
APPENDIX . . . . . . . . . . . . . . . . . . . . . 67

Table

4a.

5a.

10.

LIST OF TABLES

Incidence of hemoglobin S

Incidence of hemoglobin S in the
American black population .

Summary of samples studied

Frequencies of the hemoglobin A,
S, and C alleles in a randomly
selected population ; . . . .

Frequencies of the hemoglobin A,
S, and C alleles in nonrandomly
selected populations . . . . .

Hemoglobin genotype frequencies
for samples studied . .

Comparison of observed and
expected genotype frequencies
for samples studied . .

Frequency distributions for
unrelated persons (Male and/or
female heads of families)

Mean ages for samples studied .

Age related frequencies of
hemoglobin S . . . . . . . .

Percent of hemoglobin S in AS
individuals for age groups
studied . . . . . . . . . .

Place of birth by state (Age 18
or above) . . .

vi

Page

19
28

3O

30

31

33

34
35

38

41

42

Table
11. Relationship between age and
the sickle cell trait in
American Negroes

12. Incidence of hemoglobin S in
the United States . . . .

vii

Page

53

67

Table
11. Relationship between age and
the sickle cell trait in
American Negroes . . . .

12. Incidence of hemoglobin S in
the United States

vii

Page

53

67

LIST OF FIGURES

Figure

1. Geographic distribution of
hemoglobin 8. (Modified
from H. Lehmann and Anger
1966)

2. Percent of hemoglobin S for
age group distributions

3. Comparison of the percent of
sicklers and the mean percent
of hemoglobin S in age groups
studied . . . . . . . . . .

viii

Page

16

41

43

INTRODUCTION

Specific screening and testing for the presence of
hemoglobin S have been carried out on numerous populations
in several countries. Increased incidences have closely
correlated with the prevalence of tropical conditions con-

ducive to the abundance of the malarial parasite, Plasmo-

dium falciparum; thus the heterozygote is thought to have

 

increased fitness over both homozygotes and thereby constis
tuting a balanced polymorphism.

In the United States, the gene occurs predominantly
in the black population by virtue of their African ancestry,
but has also been reported with low frequency in other
groups. Frequency estimates for the black population have
varied from 5 to 20 percent. This variation appears due to
the variety of testing methods and the geographic area of
the country from which the sampling is derived. Most of
these determinations have been carried out on clinic or
hospital populations and are thus considered biased fre—
quency estimates.

The present study proposes to examine the frequency
of hemoglobin S and its age related frequencies in a random

sample of black residents of the Lansing, Michigan area.

The results are then compared to the frequencies obtained
from a nonrandom screening program carried out on four
other populations: a clinic and a general population from
the same area requesting evaluation, a college p0pulation

and the black residents in a State Home and Training School.

LITERATURE REVIEW

Hemoglobin S, the defect in sickle cell disease, is
an abnormal variant of adult hemoglobin A and is inherited
as an autosomal codominant. It differs from its normal pro«
totype by a single amino acid substitution in which glutamic
acid is replaced by valine in the sixth position of the beta
chain. (Ingram,1956). This molecular lesion is thought to
have arisen by a point mutation (Pauling, 1964) which re-
sulted in a change in the mRNA codon triplet from GAA or GAG
for glutamic acid to GUA or GUG for valine. This substitu-
tion has conferred upon the hemoglobin 8 molecule a variety
of chemical and physical properties which allow its isola-
tion from other hemoglobin types.

Specific chemical and physical peculiarities of
hemoglobin 8 have been well documented. In 1917, Emmel was
the first to note that after placing a drop of blood obtained
from anemic patients under a sealed cover slip, there was a
progressive increase in the number of sickled cells with the
passage of time. Hahn and Gillespie (1927) were the first
to show that the unique distortion of the sickled cell was
primarily dependent upon an alteration of the hemoglobin

from oxygen-saturated to the unsaturated state. Later

Scriver and Waugh (1930) found that the number of sickled
cells increased as oxygen decreased and carbon dioxide ac-
cumulated during venous stasis of an extremity. Pauling gt.
al,,(1949) demonstrated by free electrophoresis of carbon
monoxyhemoglobin in a phosphate buffer of 0.1 ionic strength
and at a pH of 6.9, that the hemoglobin from patients with
sickle cell anemia differed from the normal in its electro-
phoretic mobility. In 1950, Perutz and Michison showed that
deoxygenated S hemoglobin was much less soluble than deoxy-
genated normal hemoglobin. This led to the development of

a test for sickle hemoglobin based on its relative insolu-
bility by Itano in 1953. During that same year, Havinga and
Itano (1953) showed that the abnormality in sickle cell he-
moglobin resided in the globin portion of the molecule and
Singer and Singer (1953) showed that sickling, the formation
of tactoids and the tendency toward gelation were specific
characteristics of reduced hemoglobin S. Later, Murayama
(1956) found that hemoglobin 8 had a negative coefficient of
gelation since the gel of deoxygenated hemoglobin S liqui—
fies when placed at 0°C while at 20°C it is transformed into
a gel which is further facilitated by an increase to 37°C.
In attempts to explain the basis for the sickling phenomenon,
Pauling (1952) proposed that hemoglobin S molecules might be
able to aggregate or stack together in long chains because
of having complementary surface conformations. Later exper-

imental observations by Murayama (1967) suggested that the

substitution of valine for glutamic acid at the sixth posi—
tion in the beta chains allowed an intramolecular hydropho—
bic bond to form. This changed the conformation in such a
way as to allow molecular stacking and subsequent filament
formation.

It has long been known that the possession of hemo-
globin S is an inherited phenomenon. In 1949 Neel and Beet
independently proposed that it is inherited as a simple
Mendelian recessive gene to the dominant gene A for normal
adult hemoglobin. Later observations have led to the mod-
ification of this inheritance pattern to one of codominance
since the expression of both genes can be seen in heterozy-
gous individuals. Nevertheless, there remains a dispropor-
tionate predominance of the A gene product since in such
persons, hemoglobin A is more readily produced than is he-
moglobin S, their relative proportions typically being 60
percent A to 40 percent S.

In a given individual, hemoglobin S may be found
with one of a number of other hemoglobin types. McKusick
(1971) lists 59 mutants of the beta chain alone. Addition-
ally, there are 33 alpha chain substitutions. Thus the
variety of S- genotypes are many. Generally however, in
any population, only a few are common. In the American
black population for example, only the AS, SS, SC, SD, and
SB-thalassemia types are seen with relative frequency while

others are extremely rare.

The occurrence of hemoglobin S has been reported in
all parts of the world but is most common in Africa, Asia
Minor and India (Livingston 1967). Significant incidences
have been reported in the Negroes of North and South America.
In almost all instances where elevated frequencies have been
noted, they have coincided with the prevalence of malaria,

particularly the type produced by the parasite, Plasmodium

 

falciparum. Several studies have indicated that the indivi-

 

duals heterozygous (AS) for hemoglobin 8 may be at a selec-
tive advantage over their AA and SS counterparts in these
malarial areas due to differential survival and/or increased
fertility. Allison (1954) found that among school children
in Uganda, those with sickle cell trait had lower malaria
parasite rates. On examination of adults of the Luo tribe
inoculated with malaria, he found that those with the sickle
cell trait showed parasites in their blood far fewer times
than nonsicklers. Allison also showed that the frequency of
the trait in many East African tribes is closely correlated
with endemicity of malaria. Raper (1955) found a lower para-
site rate in AS individuals and was also able to show that
they did not have as many infections as nonsicklers. He
then gave conclusive evidence that those with the sickle
trait do not die as frequently from cerebral malaria which
is often a lethal complication of falciparum malaria. Sev-
eral other studies have indicated greater fertility for both

male and female AS individuals (Delbrouck, 1958; Allison,

1964; Roberts and Boyo, 1960; Fercheins, 1961; and Eaton and
Mucha, 1971). Such studies would indicate that individuals
heterozygous for hemoglobin S have increased fitness over
both AA and SS homozygotes in malarial area. This may there—
fore give rise to a stable equilibrium between the two al-
leles and constitute a balanced polymorphism.

The exact origin of the sickling gene remains un-
clear. While it is always possible that a hemoglobin may
have arisen in different parts of the world independently,
according to Lehmann and Huntsman (1966), it is possible to
interpret the present day distribution of sickling in the
world as a result of a single mutation. They indicate that
descendants of a p0pulation who occupied the ancient fertile
Arabia before the present day Semites have been recognized.
This group is thought to have been ancestors of the present
aboriginal tribes of India who may have made their way to
Africa via the former land bridge between Asia and Africa.
It is suggested that the sickling gene arose among these peo-
ple in Neolithic times and it was distributed by them east-
ward into India and westward into Africa. The finding of
high incidences among the primitive hill tribes of the neg-
roid Veddoids of southern India and southern Arabia has led
to this theory.

Despite the uncertainty of its origin, the sickling
gene presently has widespread distribution. Table l repre—

sents a modification of data compiled by Livingstone (1967)

Table 1. Incidence of hemoglobin S.

 

Frequency
Country Ranges-% Remarks

Polynesia Excludes Hawaii

Puerto Ricans 0

Negroes 2.9
Hawaii

Caucasians 0

Orientals 0.5
Micronesia - No reports
Melanesia 0
Australia 0 Only 2 small reports
New Guinea 0 Two small samples
Phillippines 0 Only one small study
Indonesia

Central Sumatra 0.4 One small study

Djakarta 0.9 One small study
Borneo - No reports
Malaya 0
Thailand - No reports
Laos — No reports
Cambodia - No reports
Vietnam - No reports
China - No reports
Taiwan — No reports
Korea 0 One small study; n=50
Japan - No reports
Ceylon 0 One small study; n=800
Andaman Islands 0 Two small samples

Table 1. Continued.

 

 

 

fgaaa
Country §§:§2:?§y Remarks
India 0 - 40
Pakistan 1.3 One small study; W. Pakis.
Iran 0 One report
Afghanistan - No reports
Iraq - No reports
Turkey 2 - 27 3
Lebanon 1 — 4.0 Avg.=0.l . 0.8
Syria 0 - 50 0 Three small samples
Israel 0 - 0.8
Jordan 0 - 0.3
Saudi Arabia 1 — 25 1
Kuwait - No reports
Aden
Arabs 1.8
Zabidis 22.8
Yemen 0 One sample, n=104
Cyprus 4 - 8.0 Two small studies
Greece 0 - 32 2 Most reports from
Macedonia. Negligible
frequencies elsewhere
Yugoslavia - No reports
Italy 2 - 4.3
Portugal 0 - 0.1 Two large samples
Czechoslovakia - No reports

Table 1. Continued.

 

1

0

 

 

Country R::§::?§y Remarks

Sweden - No reports
W. Germany - No reports
Switzerland - No reports
Netherlands - No reports
Great Britain

British soldiers 0

Preg. females of

W. Indian, Afr.

Medit. ancestry 11.
Egypt 0 - 0.2 Two samples
Libya 0.8 - 10.4
Tunisia 2.0 - 3.3
Morocco 0.5 - 2.0
Algeria 0 - 5.8 One sample: 10.3% at

E1 Golea Oasis

Mauretanie 3.9 - 12.6
Cape Verde Islands 2.8 - 7.3
Senegal 0 - 33.3 Avg. freq.=about 15%
Guinea 0 - 33.8
Portuguese Guinea 0.2 - 25.1
Gambia 6.1 - 28.4
Sierra Leone 23.8 - 30.6
Liberia 0.5 - 26.1
Ivory Coast 2.9 - 14.2
Upper Volta 2.0 - 33.8

11

Table 1. Continued.

 

w

 

Frequency
Country Ranges-% Remarks
Ghana 4.2 - 23.5
Togo 7.9 - 10.9
Dahomey 12.5 - 14.7
Niger 5.4 — 22.4
Nigeria 9.7 - 32.6
Cameroons 1.5 - 28.2
Sao Tome 4.2
Pricipe Islands 22.1
Central African
Republic
Babinga - Pygmies 16.8
Congo - Brazzaville 24.5 Small sample, n=53
Gabon 8.2 - 19.2
Congo (Kinshasa) 5.3 - 44.0 1.0% for Tutsi at
Itombwa Plateau
Rwanda and Burundi 0 - 25.9 0% in Tutsi, highest in
Bamosso
Angola 0 - 36.7 % in bushmen, highest
in Bangala
Botswana 0 - 2.0
South Africa 0 - 1.9
Mozambique 0 - 40.0 Avg. about 2%, highest
on N. Coast, Nampula
and Porto Amelia
Rhodesia, Zambia,
Malawi 0 - 27.0 Average 10-15%

Tanzania 7.4 — 40.5

12

Table 1. Continued.

 

 

 

Frequency
Country Ranges-% Remarks
Kenya 0 - 34.2
Uganda 1.0 - 39.4 Sm. Sample in Lutomi
Kraal had 46 of S3=
86.8%
Sudan 0 - 30.4 Sm. samples, avg.=5-10%
Ethiopia 0 One sm. study at Addis
Ababa
Somalia 0
Seychelles - No reports
Comoro Islands 0 - 4.7
Madagasca 0 - 23.2
Canada 1 in 6300
United States
Whites 0 - 0.7
Negroes 4.5 — 20.6
Indian 1.1 - 1.3 Small samples
Mexico 1.0 - 10.0 Avg.=3%
Guatemala - No reports
British Honduras 22.2 - 25.4
Honduras 8.0 One study on Caribs of
San Juan
El Salvador 1.1 - 1.5 Two small studies
Nicaragua - No reports
Costa Rica 3.0 One sm. study at
Terrabas

Panama 0 - 20.5 Avg. about 10%

Table 1. Continued.

 

l3

 

 

Frequency
Country Ranges-% Remarks
Cuba 5.3 - 6.5 Two sm. samples of blacks
Haiti 6.9 - 12.3
Dominican Republic 5.8 One sm. sample of Creoles
Jamaica 3.6 - 10.8
Puerto Rico
Whites 0.8
Negroes 8.4 Avg.=3.6
Lesser Antilles 1 6 - l4 0
Trinidad (Negroes) 9.3 One study, n=204
Curacao (W. Indies) 5 l - 9 2
West Indies 9.6 One study, n=998
Colombia 9 4 - l4 7 Negroes mainly
Venezuela
Non-Negroes 0 ~ 9.4
Negroes 2.5 - 6.5
Guyana — No reports
Surinam (Negroes) 10.4 - 25.0
French Guinana 1.3 - l7 9 Avg.=10%
Brazil
Whites 0 - 1.4
Mulattoes 3.0 - 15.7
Negroes 3.6 - 11.7
Chile 0 - 0.1
Bolivia - No reports
Peru - No reports
Ecuador - No reports
Burma - No reports
Iran 5.3 In patients with anemia

 

14

and reflects the frequency ranges reported from different
areas of the world other than the U.S. Unfortunately, some
populations have not been sampled for this defect while
others are represented by small samples. It is possible to
discuss, however, general trends and locate areas of fre-
quency concentrations.

Of eastern Asia and the Pacific, Livingstone notes
that there are few hemoglobin variants found in these areas,
however, the occurrence of hemoglobin S has been reported in
Polynesia and Indonesia. It is interesting to note that

Plasmodium falciparum is common in Southeast Asia without

 

the occurrence of hemoglobin S.

As indicated in Table 1, the sickle cell gene has a
wide but irregular distribution in Southern Asia, the Middle
East and Europe. In India, for example, the incidence var-
ies from 0 percent in certain tribes of the Nilgiri Hills to
estimates in excess of 30 percent in the Bestar area. In
the arid areas, the occurrences are correlated with oases
and river valleys and is thus found in oasis populations of
Saudi Arabia but not among the Bedouin desert nomads. It
has been reported sparingly in Jordon, Lebanon and Syria
while in Southern Turkey, among the Eti-Turks, frequencies
exceeding 20 percent are not uncommon. Highly elevated fre-
quencies have also been reported in Macedonia and other
areas of Northern Greece while much lower incidences occur

in Italy and Portugal. Very few studies have been carried

15

out in other European countries; however, those sampled re-
ported no hemoglobin S present in their indigenous popula-
tions.

Studies in Africa have revealed a broad belt of high
incidence of the sickling trait extending roughly across the
middle third of the continent, including Madagascar (Lehmann
33 31., 1966; see Figure 1). This area represents the
most concentrated incidence of hemoglobin S but actual fre-
quencies found here can vary quite markedly from less than
one percent to 46 percent and appears to be dependent on the
tribe sampled. Most groups show an incidence of between 12
and 30 percent. An incidence of 46 percent was found among
the pigmoids of East Africa, 33 percent in certain groups in
Senagal, Guinea and Upper Volta and over 35 percent for areas
of the Congo, Angola and Uganda. Generally there is a rapid
decrease in the gene as one proceeds either north or south
hence sickling is very rare in Egypt, Algeria and South
Africa.

The majority of sickle cell genes came to the New
World with the Eighteenth century slave ships. It is gener—
ally believed that most of the slaves were drawn from the
costal and adjacent areas of West Africa and Gambia to the
Niger River with the Congo basin making the next greatest
contribution and lesser numbers drawn from such places as
Madagascar and Mozambique (Neel, 1951). Thus the North and

South American frequencies should reflect frequencies from

16

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17

these African areas. Indeed, in the absence of malaria and
in the presence of other hemoglobin genes, a decline in fre—
quency should be realized due to elimination by natural se-
lection. Presently in Mexico and Central America, high fre—
quencies have been maintained in British Honduras (25 per-
cent) and Panama. In the Caribbean Islands, frequencies
vary on the average between 5 and 10 percent. Figures for
South America include 10.7 percent among Negroes in Caracas,
15.7 percent in Mulattoes in Brazil and up to 25 percent in
Surinam. In Puerto Rico and Brazil, frequencies of hemoglo-
bin S in the white population were 0.8 percent and 1.4 per-
cent respectively.

Sickle cell anemia was first described and charac-
terized in the United States by Herrick in 1910 in a black
West Indian male. Following this initial description, a few
isolated cases were reported. In 1923 and 1924, Sydenstricker
undertook the testing of 300 hospital patients and 1800 Ne-
gro school children and thus reported the first frequencies
of sickling in the American black population. Since that
time, numerous studies have been conducted to determine the
etiology and prevalence of the disease and the trait. Such
studies have indicated that the incidence varies in differ-
ent areas of the U.S. and may thus reflect the areas of
African origin and the degree of white admixture. The Appen-

dix documents the reported incidences of hemoglobin S in the

l8

U.S. Livingstone (1967) has summarized part of the data up
to 1967. Modifications and additions have been made which
include more recent studies and reflect the various testing
methods used.

Unlike much of the data from other areas of the
world, in the U.S., in several instances, larger samples
have been obtained. Reported sampling has been done in
twenty—four states and the District of Columbia. Most of
these, however, have been generated from hospital and clinic
populations. A few of the more recent samples have been de-
rived from sickle cell screening programs in the public
schools or at community clinics. Two samplings of military
populations have also been made. Additionally, screening
of enrollees in the Job Corps program has been done.

In this country, the average reported incidences of
hemoglobin S in the black population have ranged from 5.8
percent in Georgia to 12.1 percent in South Carolina with an
overall mean average for all states of 8.5 percent (Table 2).
The highest frequency reported from general sampling of the
American black population (20.6 percent) was noted in a
small study by Pollitzer and associates (1966) in James
Island, South Carolina. Nalbandian 33 31, (1972) found 105
hemoglobin S positives of 380 emergency room patients in
Childrens Hospital in Detroit for an incidence of 27.6 per-
cent. This represents the greatest frequency in a clinic

p0pulation. Review of studies from the literature indicates

19

Table 2. Incidence of hemoglobin S in the American black

 

 

 

population.

State or Number Number Frequency
Population sampled tested with Hng percent
California 4,028 351 8.7
Connecticut 1,358 115 8.5
District of Columbia 9,503 640 6.7
Florida 1,618 131 8.1
Georgia 2,347 135 5.8
Illinois 7,930 648 8.2
Indiana 2,355 202 8.6
Iowa 3,000 267 8.9
Kansas 1,449 132 9.1
Louisianna 2,910 246 8.5
Maryland 1,772 121 6.8
Massachusetts 650 47 7.3
Michigan 6,245 492 7.9
Mississippi 1,310 155 11.8
Missouri 2,249 203 9.0
New York 6,828 451 6.6
North Carolina 490 41 8.4
Ohio 988 79 8.0
Pennsylvania 6,101 524 8.6
South Carolina 8,197 993 12.1
Tennessee 11,473 966 8.4
Texas 24,496 2,221 9.1
Virginia 3,822 236 6.2
West Virginia 275 18 6.5
Wisconsin 9,881 931 9.4
Military 1,000 75 7.5
Job Corps 11,182 967 8.6
TOTALS 133,457 11,387 8.5

 

20

that a total of 133,457 blacks have been tested for this
defect. This figure is probably much lower than the actual
numbers tested since the results of many local screening
programs have not been published. Additionally, some stud—
ies have included blacks but racial distributions were not
reported.

While the majority of studies in this country have
been carried out in the Negro population, a few samples
have included other racial groups. Rucknagel (1964) found
an incidence of 20.2 percent in the Wesorts of Maryland.

He also reported a frequency of 1.7 percent in the Oklahoma
Indians. Lawrence (1927) found a 3.0 percent incidence in
white students of Nashville. Pollitzer, et a1. (1959) in
studies of the Lumbee Indians and an Indian triracial i50a
late in North Carolina found a frequency of 1.7 percent
while in 1966 Pollitzer and associates found in another
triracial isolate in South Carolina and the Seminole In—
dians of Florida figures of 12.2 percent and 9.6 percent
respectively. Thompson, E£.§l- (1964) in a sampling of
1045 Caucasians found one AS individual while Fielding, 33.
31. (1972) found five whites with sickle cell trait in 3426
white job corpsmen. Other workers have reported no hemov
globin S among the Caucasians tested in their samples.
(Moffitt and McDowell, 1959; Killingsworth and Wallace,
1936; Cardoza, 1957.) In a small series by Killingsworth

and Wallace (1956), an incidence of 1.2 percent was found

21

among the Mexicans of Dallas, Texas while Fielding and co-
workers (1972) reported 0.22 percent among Mexican and
Latin American job corpsmen. These latter workers also
found a 3.8 percent incidence among Puerto Ricans in their
program.

From the foregoing review of published studies of
hemoglobin S frequencies in the U.S., it may be noted that
variations in incidence may have resulted from several fac'
tors. Earlier estimates have tended to be low, perhaps due
in large measure to inadequate testing procedures. Many
of these investigators employed the simple moist prepara-
tions or sealed wet smear techniques. This resulted in a
fair percentage of false negative reactions. The later in-
clusion of two percent sodium metabisulfite as a reducing
agent gave more reliable results but still produced a num—
ber of false negatives and false positives. Other methods
such as supravital staining (Tomlison, 1941) and the test
tube method used by Neel (1951) lacked consistency of re—
sults. Furthermore, none of these testing procedures could
distinguish between the various hemoglobin S disorders. It
was not until 1953 that the development of the solubility
test by Itano and the introduction of filter paper electro«
phoresis by Spaet that test results became more accurate
and reproducible. Modifications of these two procedures
used concurrently, remain the methods of choice for current

sickle cell testing.

21

among the Mexicans of Dallas, Texas while Fielding and co-
workers (1972) reported 0.22 percent among Mexican and
Latin American job corpsmen. These latter workers also
found a 3.8 percent incidence among Puerto Ricans in their
program.

From the foregoing review of published studies of
hemoglobin S frequencies in the U.S., it may be noted that
variations in incidence may have resulted from several fac-
tors. Earlier estimates have tended to be low, perhaps due
in large measure to inadequate testing procedures. Many
of these investigators employed the simple moist prepara-
tions or sealed wet smear techniques. This resulted in a
fair percentage of false negative reactions. The later in-
clusion of two percent sodium metabisulfite as a reducing
agent gave more reliable results but still produced a num-
ber of false negatives and false positives. Other methods
such as supravital staining (Tomlison, 1941) and the test
tube method used by Neel (1951) lacked consistency of re«
sults. Furthermore, none of these testing procedures could
distinguish between the various hemoglobin S disorders. It
was not until 1953 that the development of the solubility
test by Itano and the introduction of filter paper electro«
phoresis by Spaet that test results became more accurate
and reproducible. Modifications of these two procedures
used concurrently, remain the methods of choice for current

sickle cell testing.

22

A second factor contributing to the frequency var-
iation in the U.S. appears to be due to the geographical
location of the population sampled as well as ethnic origin
and admixture with other groups. Thus the 20.6 percent in—
cidence found by Pollitzer, gt_al, (1966) seems due to the
relative isolation of this population from other groups re«
sulting in a fairly homogenous racial mixture. Similar
reasoning would account for the elevated frequencies in
other triracial isolates sampled while a markedly decreased
frequency would be noted in many nonblack populations and
in black populations where much admixing has occurred.

It may be argued that perhaps another reason for
variation could result from the methods of sampling employed.
Since the reported samples are derived from hospital and
clinic populations or nonrandom screening programs, biased
frequencies would be obtained. It seems clear, therefore,
that random sampling of populations at risk would be neceSw
sary to provide a more accurate estimate of the incidence

of this gene. To this end, the present study was conducted.

MATERIALS AND METHODS

Sampling Procedures

 

This study was composed of five samples. Sample #1
consisted of a randomly selected sample of blacks drawn from
the Lansing, Michigan black population of 12,234 according
to cluster sampling procedures and based on the 1970 census
data. The individual blocks sampled were selected in pro-
portion to the number of blacks residing there, thus, the
greater number of blacks in a particular block, the greater
the probability of selection. A total of forty-three blocks
were chosen, representing forty-three clusters of persons
and a potential sample size of 3,073.

After ascertaining the location of each of the blocks
in the sample frame, addresses were obtained and each house—
hold was sent letters of introduction to the program and our
expected visit to the residence. Each household was ap-
proached on an individual basis, requesting their participa-
tion in the program by completion of a family health survey
interview and having their blood samples drawn for subse—
quent testing.

All families were informed by letter of the results
of their tests. Those families found to contain any positive
individuals were invited to genetic counseling sessions.

23

24

Sample #2 was obtained from a mobile screening pro-
gram in the Lansing area during the month of March 1972.
This testing was performed at or near five school sites
around the community and included mainly school children
and a smaller number of adults. Sample #3 also originated
from the same general area but represents those individuals
requesting the sickle cell test through a city prenatal and
general health services clinic. Sample #4 is composed of
black students (American blacks only) enrolled at Michigan
State University during Spring quarter 1971 during the cam-
pus sickle cell campaign. Sample #5 indicates the results
of testing of all the black residents in the Lapeer State
Home and Training School, a residential facility for the

mentally retarded.

Testing Procedures

 

Blood samples of 5 to 10 cc. were collected by veni—
puncture into evacuated tubes to which EDTA (ethylene di-
amine tetraacetic acid) had been added. Other samples were
obtained by fingerprick into heparinized capillary tubes.
All samples were stored at 4°C, usually for one to three
days until electrophoresis was performed. Each sample was
divided into two parts. One aliquot was retained as whole
blood for performance of the solubility test; the other was

prepared for hemoglobin electrophoresis.

25

The solubility test used was a modification of the
method of Itano (1953) which makes use of the fact that re-
duced hemoglobin S is insoluble in a high molecular phos-
phate buffer and was prepared in the following manner: A
2.3 molar phosphate buffer was made using 165.6 gm. mono-
basic Sodium Phosphate (NaH2P04) and 156.2 gm. Dibasic So-
dium Phosphate (NazHPO4) per liter. To this was added 30
gm. Sodium Dithionite (reducing agent) and 30 gm. Saponin
(erythrolytic agent). To 2 m1. of this reagent was added
0.02 ml. whole blood. The mixture was shaken and turbidity
noted after 5 minutes incubation at room temperature. Suf-
ficient turbidity to obscure a printed background was judged
as a positive test. Both positive (hemoglobin S) and nega-
tive (hemoglobin A) controls were used with each series of
testing.

The aliquot of blood for electrophoresis was centri-
fuged at 2,000 x g for separation of plasma from the red
blood cells. After extraction of the plasma layer, the re-
sultant packed red cells were washed with five volumes of
0.85 percent saline and again centrifuged at 2,500 x g for
10 minutes. The saline was aspirated and hemolysates were
prepared by adding 0.1 ml. packed red cells to 0.5 m1.
Hemolysate Reagent (Helena Labs) then shaken vigorously to
complete lysis.

For capillary tube samples, centrifugation of the

tubes was carried out for 5 minutes for plasma-red cell

26

separation. The tubes were then cut at the plasma-red cell
interface. Hemolysates were made by adding the packed red
cells to five volumes of Hemolysate Reagent and shaken.

A linear application of 0.5 - 1.0 microliter of
hemolysate was placed on the cathode side, one inch from
the end of a blotted cellulose acetate plate which had been
presoaked in the electrophoretic buffer solution for 20 min-
utes. The plates were then placed in the electrophoretic
chamber (Thomas Model 20) filled with Supre-Heme buffer,
pH 8.6 (Helena Labs) and supported by two fixed bridges
which were covered with cheese cloth layers to insure pro-
per wicking action. Electrophoresis was carried out by the
application of a current of 2mAmps per plate for 20-25 min-
utes. The plates were then removed and placed in Ponceau
S stain for 10 minutes. Excess stain was removed by two
consecutive washes in 5 percent acetic acid followed by a
2 minute dehydration in 95 percent ethanol. Clearing was
accomplished by soaking each plate for at least 2 minutes
in a solution of glacial acetic acid in ethanol (25 ml.
acetic acid in 75 m1. ethanol) and then allowed to dry in
air, before interpretations were made.

Upon obtaining the dry, cleared cellulose acetate
plate, determination of the hemoglobin type was made by its
comparison with electrophoresed hemoglobin controls (Helena
Labs) and the results of the solubility test. For all those

presenting hemoglobin S patterns, further densitometric

27

readings were made to determine the percentages of the var-
ious hemoglobins present (S, A1 and A3, A2 and F), by use
of a Densicord densitometer (Photovolt, Inc.). These deter-
minations were performed on the random sample population

only.

RESULTS

All sampling and testing of the five black popula-
tions were carried out between March 1971 and June of 1972
and resulted in a total of 4,208 individuals screened.
Table 3 summarizes the numbers obtained from each of the
samples studied and shows that approximately 44 percent of
those tested were in the randomly selected group while 22
percent were from the Mobile Unit screen, 21 percent from
the campus testing with the Clinic and State Home Screens
contributing smaller percentages of 8 percent and 5 percent
respectively. Since participation in the random group was
by consent, the 1841 individuals in this group represented

close to 60 percent of the total anticipated. Both refusals

Table 3. Summary of samples studied.

 

 

 

Sample Number Percent of
Number Origin of Sample Tested Total
1 Random Selection 1841 43.75
2 Mobile Screen 943 22.41
3 Clinic Screen 343 8.15
4 Campus Screen 883 20.98
S State Home and Training 198 4.71
School
TOTAL 4208 100.00

 

28

29

of individuals to consent to be tested and inaccuracy of
census data to provide correct locations of black residents
contributed to the decreased size of this sample.

"’From,theresults obtained in the random sample,
calculations of the frequencies of the hemoglobin A, S, and
C alleles were made directly (see Table 4). The gene fre-
quency for hemoglobin A was found to be 0.945 while the S
and C alleles have values of 0.042 and 0.012 respectively.
Frequencies of these three alleles were calculated for sam«
ples 2 thru 5 in the same manner. These values are re-
corded in Table 4a.

Table 5 indicates the actual hemoglobin genotype
frequencies obtained from each population studied. The
combined percentages of those with S in the samples varied
from 6.2 in the mobile screen to 9.0 in the clinic popula«
tion. The randomly selected group was 8.42 while the cam-
pus and Training School was 6.7 and 7.6 respectively.

Table 5 also shows that the incidence of hemoglobin C was
2.4 in the random sampling, 2.97 in the mobile screen,

4.08 in the clinic population, 2.71 in the campus sample

and 3.03 in the Training School group. The combined C fre—
quency was 3.87 percent and includes the AC, SC and CC
genotypes. The combined incidence of individuals with ele—
vated levels of fetal hemoglobin (F) was 1.12 percent for
all groups and six individuals were found to have hemoglobin

types other than the A, S, C and elevated F. None of the

30

Table 4. Frequencies of the hemoglobin A, S and C alleles
in a randomly selected population.

 

 

Genotype No. Individuals A S C

 

 

AA 1641* 3282 0 0
AS 152 152 152 0
SS . 3 0 6 0
AC 44 44 0 44
CC 1 0 0 2
TOTALS 1841 3478 158 46
Frequency of alleles .945 .043 .012

 

a
Includes both AA and AAF+ individuals.

Table 4a. Frequencies of the hemoglobin A, S and C alleles
in nonrandomly selected populations.*

 

 

 

Sample Number A S C
2 .953 .031 .015
3 .933 .047 .020
4 .965 .034 .001
5 .944 .041 .015

 

a
Calculations were made directly by same method
used in Table 4.

31

 

 

 

Table 5. Hemoglobin genotype frequencies for samples studied.

Sample AA SS SC AC
No. # # % % % # %
1 1623 88.16 152 8.26 .16 0 44 2.39
2 848 89.73 57 .04 0 0 28 2.97
3 277 80.76 30 .71 .29 0 14 4.08
4 798 90.37 58 .57 0 .11 23 2.60
5 175 88.38 14 .07 .51 0 6 3.03

Totals 3721 88.43 311 .39 .14 .02 115 2.73

 

 

 

 

CC AAF+ Others S-thal Totals
% # % # % # % # %
.05 18 .98 0 0 0 0 1841 100
0 6 .64 3 .32 1 .11 943 100
0 21 6.12 0 0 0 0 343 100
0 1 .11 2 .23 0 0 883 100
0 l .51 l .51 0 0 198 100
.02 47 1.12 6 .14 l .02 4208 100

 

33

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34

genotypic frequencies obtained were found to be signifi-
cantly differently from those expected from Table 4. (See
Table Sa.)

The random sampling was derived from family group-
ings. A frequency distribution was made, therefore, in
Table 6 for unrelated males and/or female heads of families
to compare with overall results or to note any effects of
combining family group data. It was found that the inci-
dence of the AS genotype was 8.39 percent for males and a
slightly lower frequency of 7.36 percent for females for a
combined average of 7.7 percent. The occurrence of the AC
genotype in this group was 2.2 percent and one male was
found to have elevated F. No other genotypes were found.

Table 6. Frequency distributions for unrelated persons
(Male and/or female heads of families).

 

 

 

AA % AS % AC % AAF+ % Total %
d 255 89.16 24 8.39 6 2.09 1 0.35 286 100
g 393 90.34 32 7.36 10 2.29 O 0 435 100

Total 648 89.86 56 7.77 16 2.22 1 0.14 721 100

 

Total Sample = 1841
Number of Families = 537
Average Family Size = 3.43

In Table 7 the mean ages for each sample with re-

spect to hemoglobin types were tabulated. This was done for

35

Table 7. Mean ages for samples studied.*

 

AA AS SS SC

Sample # Mean # Mean Mean # Mean
No. ‘ Age Age Age Age

1 1603 21.19 151 22.67 14.0 0 0

2 844 15.05 57 15.33 38*** 0 0

3 265 16.9 30 14.8 1** 0 0

4 783 20.4 58 19.7 0 1 20**
Totals 3495 19.21 296 19.87 16.2 1 20.0

 

.

Ages were not recorded for sample #5.

*1:

S-thalassemia.

Only one individual in the category.

ll

36

 

CC AAF+ Others Total
Mean Mean Mean Mean Mean
Age Age Age Age Age
44 18.0 4** 18 28.17 0 1820 21.24
28 17.43 0 6 9.83 22.0 938 15.14
12 18.3 0 21 7.1 0 329 16.1
22 20.1 0 1 26** 24.7 868 20.37
106 18.31 4.0 46 16.11 23.6 3755

 

37

samples 1-4 only since no ages were recorded for sample #5.
As can be seen, the total mean ages of all individuals in
these samples were 21.29, 15.14, 16.1 and 20.37, thus the
clinic and mobile screens included more younger individuals.
Comparisons of ages of AA persons to those with AS genotypes
showed little variability in that two samples showed a
higher mean age for AS individuals, while in two groups the
mean ages were higher in AA individuals. Differences in
mean ages for both genotypes were not significant in any of
the samples and varied between 0.7 and 2.1 years with an
average of 1.14 years. For the SS, SC and Sethalassemia
persons, no strict comparisons could be made due to the
small number of individuals in these categories. The same
is true for the single CC person and those with elevated
fetal hemoglobin as well as those who were found to possess
other undetermined hemoglobin types. It was also noted

that the total mean age for all persons with the AC genotype
was 18.31. This compared favorably with the 19.21 years for
the total mean age for all AA persons.

Table 8 shows the age related frequencies of indi-
viduals with S genotypes in samples 1-4. The subjects were
divided into ten age groups for comparison purposes. From
these data, it can be seen that the percentage of S affected
individuals is variable within each sample group. There is
also no consistency with respect to age between samples.

Generally, however, there seem to be some random fluctuations

38

Table 8. Age related frequencies of hemoglobin S.

 

 

Age Sample #1 Sample #2

Gr°uP5 % of % with % of % with
(yrs) Total # of S Sample 8* Total # of S Sample S
0-4 230 16 12.64 7.0 85 7 9.0 8.2
5-8 244 14 13.41 5.7 194 8 20.7 4.1
9-12 221 16 12.15 7.2 236 15 25.1 6.4
13-17 255 30 14.01 11.8 181 12 19.3 6.6
18—25 296 27 16.3 9.1 87 6 9.3 6 9
26-35 210 18 11.5 8.6 91 5 9.7 5.5
36-45 161 16 8.9 9 9 43 3 4.6 6.8
46-55 99 7 5.4 7.1 16 2 1.7 12.5
56-65 77 7 4.2 9.1 3 0 0.3 0
66 + 24 3 1.3 12.5 3 0 0.3 0

 

 

 

% with S includes all S genotypes.

39

 

 

 

Sample #3 Sample #4
% of % with % of
Total # of S Sample S Total # of S Sample
98 11 29.8 11.2 - — -
36 4 10.9 11.1 - - -
26 l 7.9 3.8 - - -
25 5 7.6 20.0 4 0
68 4 20.7 5.9 812 38 93.
48 3 14.6 6.3 40 l 4.
18 2 5.8 11.1 11 0
8 l 2.4 12.5 1 0
1 0 0.3 0 - -
l 0 0.3 0 — -

 

 

40

producing three peak age periods in these persons in the
groups 0-8 years, 13-17 years and age 36 and above (see
Figure 2). Note, however, that in all samples this latter
group constituted a relatively small percent (less than 20
percent) of their respective samples.

In Table 9, the percent of hemoglobin S in the AS
individuals for the various age groups was tabulated. As
indicated, the amount of S varied from 24.3 to 49.3 percent,
with an overall average of 38.38 percent for all groups.
Furthermore, the amount of S also varied slightly within
each specific age grouping. When the mean percents of each
age group were compared, the values obtained showed differ-
ences of less than four percent despite the small number of
persons in some of the categories.

In an effort to compare the percent of sicklers with
the mean percent of hemoglobin S for the age groups, Figure
3 was constructed from data in Tables 8 and 9. This was
done for the random sample only. It can be seen that in
spite of the small fluctuations in the mean amount of S for
each group, the percent of sicklers in the age groups ap-
pears to vary inversely with the amount of S hemoglobin.
This relationship holds for all age groups except in the
category of age 66 up.

To facilitate comparisons of the random sample pop-
ulation to other geographical areas of the U.S., the places

of birth by regions were tabulated for individuals eighteen

41

 

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Figure 2.

42

Table 9. Percent of hemoglobin S in AS individuals for
age groups studied.

 

 

 

Hemoglobin S Mean % Std.
Age Group % - Range of S Deviation

l. 0 - 4 32.8 - 42.1 37.56 2.72
2. 5 — 8 35.0 - 54.7 39.93 3.25
3. 9 - 12 30.8 - 44.7 38.1 3.24
4. l3 - 17 30.5 — 45.5 37.43 3.51
5. 18 - 25 31.5 - 45.2 39.30 3.6

6. 26 - 35 33.1 - 49.3 39.74 4.43
7. 36 ~ 45 26.9 - 43.4 36.59 4.58
8. 46 - 55 36.3 - 42.3 40.3 2.47
9. 56 - 65 24.3 - 41.7 36.78 5.9
10. 65 up 32.8 - 47.7 39.8 5.3

Mean % of S for all AS individuals = 38.38

43

Mean percent of Hng in AS individuals

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44

or older in Table 10. It was found that the majority of
these persons originated from the deep south central states
of Alabama, Louisianna, Mississippi, Arkansas and Tennessee
(51.22 percent) while 27.6 percent came from the immediate
Midwestern states of Michigan, Illinois, Indiana and Ohio
with all the other regions combined giving a total of 21.16

percent.

 

45

 

 

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moo NH.H oH v.o m m.o mm N.HH oo N.Hm New o.n~ omN H<Hoe
HH o o o o ~.o N NH.o H o.o u NH.o H +m<<
o o o o o o o o o o o o o uu
oH o o o o <.o m NH.o H o.H o om.o m u<
H o o o o o o o o NH.o H o o mm
on N.o N o o u.o o o.H o o.v ov N.N oH m<
emu No.o o e.o m N.u No o.o mo u.e¢ mom n.¢~ mHN <<
mHmuoH o a m H m a m H o H m H omxuoaoo
oH whonpo UHpcmHu< ausom-on kumou.nu30m Hwnpamu pmoonz
H nuhoz -nusom moon opwHooEEH
o>o
m m a u m <

 

 

.no>onw no oH ow<v ouwum kn nuHHH mo oomHm .oH oHan

 

45

 

 

.mopmpm Hoauo HH< - m aonom
.p> .Hm ..::ma .Hz .42 .mz ..::oo ..mma2 ..m: - m :onom
.mcwx ..mHHo ..m> .3 ..xx ..xoe ..oz - n :onom
.mHm ..mo .um .02 ..a> ..oz - o :onom
.caoh ..HH< ..mmHE ..MH ..wH< - m onwom
.oHeo ..e:H ..HHH ..equ - < eonom
Noo NH.H oH ¢.o m m.o mm N.HH om N.Hm Nee o.NN omN H<HOH
HH o o o o N.o N NH.o H o.o N NH.o H +m<<
o o o o o o o o o o o o o 00
oH o o o o ¢.o m NH.o H o.H o om.o m u<
H o o o o o o o o NH.o H o o mm
on N.o N o o u.o o o.H o o.v ow N.N oH m<
own No.o o e.o m N.N No o.o mo N.vv mom N.¢N mHN <<
mHmuop * a a a a a a a a a a a maxpoqoo
oH whoapo oHucmHu< nusom-on Hmumoulnu3om Hanudou pmoonz
Ho> :uuoz -Apsom moon opmHoofieH
o
m m a u m <

 

 

.flo>onw no oH om<v oumum kn :uHHn mo oomHm .oH oHan

DISCUSSION

The pathology and frequently fatal outcomes of in—
dividuals homozygous for hemoglobin S at early ages has
long been recognized. The importance of the sickle cell
trait in individuals heterozygous for this defect has been
recently underscored as potentially fatal in special situa-
tions involving oxygen deprivation. Other hemoglobin S
genotypes such as SC disease and S-B thalassemia have also
been shown to lead to complications under certain condi~
tions. At present, then, there is the need to identify in-
dividuals who are affected, for their own health reasons
as well as for the potential risks to their future off-
spring.

Not insignificant also is the need to obtain exten-
sive incidence data and age related frequencies to make in-
telligent assessments of the prevalence of this defect and
to determine the fitness of these various S-genotypes in
the absence of any obvious selective advantages. Rucknagel
and.Nee1 (1961) have stated that "although it may seem an
anachronistic stand in these days of biochemical excitement,

in the opinion of the authors, the outstanding gap in our

5

knowledge of the population genetics of the HbB

gene is this

46

47

question of the age—incidence trend under nontropical con-
ditions." Since this statement by these authors, little
has been done to illuminate this area. Those studies which
have been undertaken have traditionally used hospital pop-
ulations.

In the present study, both random and nonrandom
populations were examined and resultant gene and genotype
frequencies compared in an effort to detect and eliminate
any biases which may have been included in earlier samp-
lings. The data obtained from all of the five samples
studied were consistent. When calculation of gene frequen-
cies of the three hemoblobin alleles A, S, and C were made
and the expected genotype frequencies were computed, the
subsequentrx2 analysis for each sample revealed no signi-
ficant differences between these and the observed genotype
frequencies in any of the samples despite the differences
in methods of sampling and ascertainment.

The individuals in sample #1 were randomly selected
and located from census information. Contacts with them
were made directly by letter and subsequent home visit when
health surveys and blood samples were taken with their con-
sent. While it may be argued that the lack of consent by
some individuals so selected may in itself constitute a
bias, it seems unlikely that any correlation would exist
between an individual's hemoglobin type and his consent or

refusal to be tested. Indeed a sampling of the reasons for

48

refusals indicate reasons such as age, preference of test-

ing by family physicians, fear of needles and indifference

to testing programs in general. A few declined due to pre-
viously being tested for this defect.

Strict comparisons of the frequencies obtained from
sample #1 are difficult since there are no other random
samplings from this geographical area reported in the lit—
erature. Only one other random study has been published.
This was made by Boyle and coworkers (1968) in Charleston,
S.C., an area of the U.S. which has consistently reported
the highest hemoglobin S frequencies in North America.
Moreover, in their study, no individuals under age 35 were
included. Despite this limitation, these workers did re-
port some age incidence data which will be discussed later.

Although there have been no other random samplings
to use as comparisons, the average frequency of 8.2 percent
for AS individuals from sample #1 compares favorably with
the overall frequency for Michigan of 7.9 percent as re«
ported in Table 2. This combined frequency for the state
represents the results of four studies. Cooley and Lee
(1926) and Neel (1951) from samples of Negro hospital pa-
tients obtained frequencies of 7.5 and 9.1 respectively.
Nalbandian, g£_al. (1971), in a sample of black school chil-
dren, found an incidence of 6.0 percent. In a 1972 study
of black emergency room patients, Nalbandian g£_al. re-

corded a frequency of 13.7 percent for AS individuals.

49

This latter value as well as the overall incidence for all
hemoglobin S genotypes of 27.6 percent found by these
workers, differs greatly from other reported data for Mich-
igan and is probably due to the method of sampling utilized.
Upon consideration of this potential bias and noting the
small size of the sample, it may be concluded that these
frequencies are probably not significant. If one excludes
this latter study from the frequency calculations for the
state, the value obtained is reduced to an overall inciv
dence of 6.6 percent. This figure is still not signifia
cantly different from the 8.26 percent found in the random
sample of the present study.

Additional comparisons of the 8.26 percent value
from this study with the data published for other areas of
the Midwest are again favorable since the average frequen—
cies reported for Illinois, Ohio and Indiana were 8.2 per-
cent, 8.0 percent and 8.6 percent respectively. These are
also in.agreement with values reported for Louisiana of 8.5
percent and Tennessee of 8.4 percent, the states from which
much of the Michigan black population has originated.

As has been noted, the pooling of family group data
in sample #1 has little if any effect on overall frequency
since the frequency values for unrelated males and females
correlated closely with the combined data. In the males

and females thus compared, however, a slightly higher

50

incidence was found in the males but this difference was
not statistically significant.

As indicated earlier, sample #2 individuals were
the results of a mobile screening program in which persons
requesting sickle cell evaluations came to different sites
for testing. Since most of these were located in school
facilities, this sample contains a disproportionate number
of school aged children, hence a lower mean age. This sam«
ple would, therefore, be comparable to the many current
school screening programs across the country. While its
overall results documented here are not significantly dif—
ferent from the random population, its frequency of 6.04
percent for the AS genotype is almost identical to the 6.0
percent found in a similar group in Grand Rapids, Michigan
black school children by Nalbandian, g£_al, (1971).

The population in sample #3 was derived from a
health services clinic and is, therefore, typical of many
previous studies. The lower mean age of 16.1 years for
this group is due to the larger number of young females
attending the prenatal facilities. That these mothers sub—
sequently brought their young children in for testing is
reflected in the relatively large number of infants in this
sample with an excess of elevated fetal hemoglobin. The
frequencies reported here are also well within limits for
all genotypes despite the slightly higher incidence of the

AC persons of 4.08 percent.

51

In sample #4, a college population was sampled.
Results reported here were calculated for American black
students only although other groups were tested. Again,
none of the frequencies derived deviated significantly from
those predicted. Even the mean age more closely approxi-
mated that of the random sample than that of any of the
other nonrandom groups. Additionally, the AS frequency of
6.57 percent is in close agreement with that of 7.0 percent
reported by Rhatigan (1972) in Negro college students in
Witchita, Kansas.

For sample #5, the smallest group, the black resiv
dents of the Lapeer State Home (institution for the men-
tally retarded) were tested. As with sample #1, there are
no published studies of this type with which to make com-
parisons, however, as indicated, no significant differences
were obtained from this data.

As previously suggested, there is a need to explore
the question of age-incidence trends for the hemoglobin S
gene, especially in relationship to the AS genotype under
nontropical conditions. If there are certain disadvantages
to this sickle cell trait as recent case reports have a1-
luded, one would expect a significant decline in the num-
bers of these carriers in older age groups. In the present
study, no such decline was noted. This finding is at vari-

ance with some of the earlier age incidence studies but is

52

in agreement with others. Table 11 summarizes results
from these studies.

In the first four series (Diggs, et 31., 1933;
Switzer, 1950; Neel, 1951; Pollitzer, 1958), all based on
hospital patients, agree in indicating less sickling among
older patients. The results could be interpreted as comv
patible with less disease (and less cause for hospitaliza-
tion) in older sicklers or a higher death rate on the part
of sicklers. Neither of these alternatives seem plausible
in view of the study by McCormick and Kashgarin (1965),
also on hospital patients which found no decrease in the
sickle cell trait percentages with increasing age. More-
over, these same workers, when comparing death rates by
age of 305 individuals found to have sickle cell trait
upon autopsy to those autopsied without the trait, failed
to demonstrate a significant decrease in the number of
sicklers with increasing age but did find random fluctua-
tions in the percent of AS individuals in some age groups.

Other studies including the present one have con-
curred with these latter findings. Rucknagel (1961) for
example, found an increase in the percentages of AS indi-
viduals in older age groups since this figure was 19.1 per-
cent in groups from 0-50 years but was 26.1 percent in per-
sons aged 50 or older. Petrakis, 33 31. (1970) found a
slight decrease in the trait with age but it was not sta-

tistically significant. Boyle, gt a1. (1968) found no

53

Table 11. Relationship between age and the sickle cell
trait in American Negroes.

 

 

Investigator

Age

Number

Group Tested

Number

Percent

Sickling Sickling

 

Diggs, g£_al., 1933

Switzer, 1950

Neel, 1951

Pollitzer, 1958

Rucknagel and Neel,
1961

McCormick and
Kashgarin, 1965

Boyle, gt_a1., 1968

Petrakis, et al.,
1970

Present Study all
samples combined

6-20
21-50
51-

6-20
21-50
51-

12-20
21-50
51-

14-29
30-

0-20
21-50
51-

11-20
21-50
51+

35-44
45-54
55-64
65+

5-20
21-49
51+

0-17
18-35
36-55
56+

1,112
1,102
403

843
1,233
302

147
703
146

232
241

1,476
530
176

126
657
630

335
183
140
117

417
2,665
946

1,835
1,652
356
109

108
96
28

130
165
42

15
67
7

42
26

282
101
46

ommu
t94>0L>

 

54

evidence of an age trend in adults nor a decrease in the
prevalence of the trait in older persons although this sam-
ple excluded persons under age 35. In the present study a
slight though not significant increase in the percent of

AS individuals with age was observed. This may possibly

be due to the small numbers of individuals included in
these latter age groups. Clearly, the majority of evidence
would tend to indicate that AS individuals are not at any
great risk for early death due to sickle cell trait.

The additional finding in this study of similar
fluctuations in the S frequency in all samples examined is
interesting. While other workers have reported frequency
changes for certain age groups, comparisons are difficult
since the age categories of each were variable with most
groupings encompassing a wide range of ages. When the pres-
ent age data were grouped in this manner, no significant
differences were observed. Furthermore, regression analy-
sis of the small changes in the mean percent of S hemoglobin
produced by the different age groups and subsequent t-values
also indicated no significance. Thus in this study, the
changes in the frequencies of hemoglobin S genotypes in cer-
tain age groups and the amount of S produced by them may
show random variation from time to time but is not statis-

tically significant.

CONCLUSIONS

The principle purposes of this study were to deter-
mine the incidence and age related frequencies of hemoglobin
S in random and nonrandom populations. Specific screening
of 4208 black individuals for hemoglobin S was conducted by
use of cellulose acetate electrophoresis and by determina-
tion of hemoglobin solubility in a 2.3 molar phosphate buf-
fer. Of the five sample groupings generated, one resulted
from a random selection process. The random grOUp was com-
pared to the results of a nonrandom school-community screen-
ing program, and a clinic population from the same general
area, a sample of college students and one sample from a
State institution for the mentally retarded.

The frequency of the hemoglobin S allele in the ran-
dom sample was found to be 0.043. No significant differ-
ences were found between this figure and the allele frequency
in any of the nonrandomly selected groups although the cor-
responding values varied from 0.031 to 0.047. When the in-
cidences for the AS genotypes were compared, the value for
the random population was 8.3 percent, for the general screen
it was 6.2 percent, the clinic population was 8.8 percent,

the college group, 6.6 percent, and the institution was 7.1

55

56

percent with a mean AS frequency for all samples of 7.39
percent. While these values are slightly lower than the
national average of 8.5 percent, they are in agreement with
other figures reported for Michigan by other workers as
well as with values for the Southern states from which the
Michigan population has originated.

Examination of the age related frequencies revealed
no significant differences in the number of individuals
with hemoglobin S. This finding was consistent in all sam-
ples, despite the differences in the mean ages of the sam-
ples due to the methods of ascertainment. The mean percent
of hemoglobin S fluctuates with age but those values were
not statistically significant.

The results of this study have two major implica-
tions. Firstly, the incidence of hemoglobin S is no dif-
ferent whether the samples are randomly or nonrandomly se-
lected. The frequencies obtained from both selection meth-
ods will be similar providing they are drawn from sympatric
populations. The second and perhaps more significant im-
plication is the finding of the lack of any decline in the
frequency of AS individuals with age in a non-malarial en—
vironment. Within the limits of the population size sam-
pled, this implies the lack of negative selection pressure
against these individuals as some of the current literature
has alluded. While a study of this nature does not explore

the overall fitness of the AS genotype, it does suggest that

57

these individuals are not at any great risk for a shortened
life span. In this regard, this study should prove reassur-

ing to these persons as well as informative to the genetic

counselor.

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Bulletin N.Y. Acad. Med., 40:334.

 

Perutz, M. P., and Michison, J. M. 1950. ”State of Hemo-
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Petrakis, N. L., et g1. 1970. "Prevalence of Sickle-Cell
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Pollitzer, W. S. 1958. ”The Negroes of Charleston, S.C.:
A Study of Hemoglobin Types, Serology and Morphol-
ogy." Am. J. of Phys. Anthropology, 16:241-263.

Pollitzer, W. S., et g1. 1959. "Hemoglobin Patterns in
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Pollitzer, W. S., et g1. 1966. "Factors in the Micro-
evolution 3f a Triracial Isolate." Am. J. Hum.
Genet., 18:26-38.

 

Pollitzer, W. S., et g1. 1966. Unpublished Observations.
Cited in LIVingstone, 1967.

 

Raper, A. B. 1955. "Malaria and the Sickling Trait."
Brit. Med. J., 1:1186.

 

Rhatigan, J. J., Mitchell, R. L., and Cawley, L. P. "Test-
ing for Sickle Cell Anemia." JACHA, 20:387.

64

Roberts, D. F., and Boyo, A. E. 1960. "On the Stability
of Haemoglobin Gene Frequencies in West Africa.”
Annals of Human Genetics, 24:375-387.

 

Rosenblum, R., Kabakow, B., Lichtmon, H. C., and Lyons,
H. A. 1955. "Sickle Cell Trait and Disease in
Pulmonary Tuberculosis." Arch. Int. Med., 95:540.

 

Rosner, F., Tatsis, B., Calas, C. F. 1972. "Screening for
Sickle Cell Disease and Related Disorders.” JAMA,
219:1472.

Rucknagel, D. L. 1957. "Paper Electrophoresis Survey of
Hemoglobins of American Indians." J. of Lab. 6
Clin. Med., 49:896-899.

 

 

Rucknagel, D. L., and Neel, J. V. 1961. "Hemoglobin-
opathies." Prpg, Med. Genet., 1:158.

 

Rucknagel, D. L. 1964. "The Gene for Sickle Cell Hemo-
globin in the Wesorts: An Extreme Example of Genetic
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University of Michigan.

Ryan, J. J., et a1. 1960. "Sickle Cell Trait and Tubercu-
losisT“'"Am. Rev. of Resp. Diseases, 81:546-549.

 

Schneider, R. G. 1954. "Incidence of Hemoglobin C Trait
in 505 Normal Negroes: A family with Homozygous
Hemoglobin C and Sickle Cell Trait Union." J. Lab.
8 Clin. Med., 44:133-144.

 

Schneider, R. G. 1956. "Incidence of Electrophoretically
Distinct Abnormalities of Hemoglobin in 1550 Negro
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1270-1276.

 

Schriver, J. B., and Waugh, J. R. 1930. "Studies on a Case
of Sickle Cell Anemia." Canad. Med. Assoc. J., 23:
2375.

 

Singer, K., and Singer, L. 1953. "Studies on Abnormal
Hemoglobins. VIII. The Jelling Phenomenon of Sickle
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Smith, E. W., and Conley, C. L. 1953. "Filter Paper Elec-
trophoresis of Human Hemoglobin with Special Ref-
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94-106.

 

65

Smith, J. H. 1928. "Sickle Cell Anemia." Med. Clinics
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Standard, R. L. 1972. "Sickle Cell Anemia, A Public
Health Problem in the District of Columbia."
Medical Annals of D.C., 41:304.

 

Switzer, P. K., and Fouche, H. H. 1948. "Sickle Cell
Trait: Incidence and Influence in Pregnant Colored
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Switzer, P. K. 1950. "The Incidence of the Sickle Cell
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Sydenstricker, V. P. 1923. "Discussion of the Blood Pic-
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Thompson, R. B., et a1. 1964. "A survey of Hemoglobin-
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Tomlinson, W. J. 1941. "Studies of Sicklemia Blood with
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Trouillot, L. 1972. :Brooklyn Screens for Sickle Cell
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1011.

 

Watson, J., et a1. 1948. "The significance of the Paucity
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Weatherall, D. J. 1963. "Abnormal Haemoglobins in the
Neonatal Period and their Relationship to
Thalassaemia." Brit. J. Hematol., 9:265—277.

 

Webb, 2. O. 1972. "Sickle Cell Anemia: A Clinical Screen-
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Weiss, W., and Strecher, W. 1952. "Tuberculosis and Sickle
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66

Whalley, P. J., et a1. 1963. "Sickle Cell Trait and Preg-
nancy." ‘UAMA, 186:1132-1135.

Whalley, P. J., Martin, F. G., and Pritchard, J. A. 1964.
"Sickle Cell Trait and Urinary Tract Infection
During Pregnancy." JAMA, 189:903.

APPENDIX

 

APPENDIX

Table 12, Incidence of hemoglobin S in the United States.

ti
f4—

 

 

 

Population type Number Methmb
Reference Year Place and characteristics tested used*
Greenberg 1970 Boston, Mass. Negro children-
Head start program 650 5
TOTALS Massachusetts NEGRO 650
Barnes gt_§1, 1972 New Haven, Negroes-pediatric
Conn. health center 1000 2
Barnes gp_§l, 1972 New Haven, Negro hospital
Conn. patients 358 2
TOTALS Connecticut NEGROES 1358

*Testing Methods Used

Sealed coverslip on slide - no sodium metabisulfite
Electrophoresis

Moist preparation

Sickle cell preparation - with sodium metabisulfite
Solubility test

Test tube method

Supravital staining

Cited in Livingstone (1967)- methods not given.

Not Given

LOWVO‘m-thl-J

67

68

 

 

 

Overall % 'Percent Percent Percent Percent Percent Others
sickle cell SS AS AC SC AD

47(7.3%)

47(7.3%)

70(7.0%) 2(0.2%) 67(6.7%) 26(2.6%) l(0.l%) 11(l.1%)
45(12.6%) 2(0.6%) 42(11.S%) 14(4.0%) l(0.3%) 4(l.l%)

115(8.5%)

 

69

Table 12. Continued.

 

 

Number Methods
tested used

Population type

Reference Year Place and characteristics

 

Negro-babies and
Hospital patients 150 l

Wallstein and

Kreidel 1928 New York, N.Y.

Dolgopol and

Stitt 1929 New York, N.Y. Negro-TB patients 77
Rosenblum
g£_al. 1955 Brooklyn, N.Y. Negro-TB patients 200
Trouillot 1971 Brooklyn, N.Y. Negroes-Clinic approx.
4500
Levy 1929 New Rochelle, Negro-
N.Y. Hospital patients 213
Watson 1948 Long Island, Negro-newborns
N.Y. and mothers 226
Kelly 1966 Albany, N.Y. Negroes-Headstart 134
Rosner 1971 Queens, N.Y. Negroes-Clinic
patients 1328
TOTALS New York NEGROES 6828
Beck and
Hertz 1953 Philadelphia, Negro maternity
Pa. patients and 100
children
Margolies 1951 Philadelphia, Negro clinic and
Pa. Hospital patients 1000
Myerson 1959 Philadelphia, Negro-hospital
Pa. patients 1000
Weiss and
Strecher 1952 Philadelphia, Negro TB patients 150
Pa.
Weiss and
Strecher 1952 Philadephia, Negro-hospital
Pa. patients 150

70

 

 

Overall % Percent Percent Percent Percent
sickle cell SS AS AC SC

Percent
AD

Others

 

13(8.66%)

4(5.2%)

l6(8.0%) 1(0.5%) 15(7.5%)

270(6.0%)

12(5.6%)

18(8.0%)
12(8.96%)

106(8.0%) 105(7.9%) 32(2.4%) l(.08%)
451(6.6%)

13(13%)

72(7.2%)

79(7.9%) 3(0.3%) 74(7.4%) 23(2.3%) 2(0.2%)

19(12.6%)

8(5.3%)

12(0.9%)

4(0.4%)

71

 

 

 

 

Table 12. Continued.
t
Population type Number Methods
Reference Year Place and characteristics tested used
Laros 1967 Philadelphia Negro clinic patients 3701 2 and 4
TOTALS Pennsylvania NEGROES 6101
Josephs 1928 Baltimore, Md. Negro children and
random hospital 250 9
selection
Smith and
Conley 1953 Baltimore, Md. Negroes-hospital
outpatient clinic 500 2
Weatherall 1963 Baltimore, Md. Negroes-cord blood
samples 900 2
Boyer et a1. 1963 Maryland Unrelated Negroes
"""_’ prisoners, hospital 681 2
personnel, preg.
women
Rucknagel 1964 Maryland- Wesorts
Charles and Triracial Isolate 2578 2
Prince George
Counties
Rucknagel 1964 Charles County Negroes 191 2
Maryland
TOTALS Maryland NEGROES 1772
Ryan g; _l. 1960 Washington, Negroes-Preg.
D.C. females 3000 2 and 4
Jenkins and
Clark 1962 D.C. Negroes-prenatal
clinic 828 2
Ryan.et 21. 1960 D.C Negro TB patients 330 2 and 4
McCurdy 1964 D.C Negroes-prenatal
clinic 3333 2 and 4
McCurdy 1964 D.C Hospital employees 328 2 and 4

72

 

 

 

Overall % Percent Percent Percent Percent Percent Others
sickle cell SS AS AC SC AD
333(9.0%) 3(0.008%) 320(8.7%) 7(0.02%) 3(0.008%)
s-thal
524(8.6%)
l6(6.4%)
42(8.4%) 5(1.0%) 36(7.2%) 9(l.8%) l(0.2%)
67(7.4%) 67(7.4%) 26(2.8%) 23(2.6%)
44(6.5%) 44(6.5%) 11(l.6%)
520(20.2%) 20(0.78%) 496(20.2%) 5(0.19%) 4(0.l6%)
10(5.2%) 10(5.2%) 4(2.1%)
121(6.8%)
201(6.7%)
37(4.5%) l(0.12%) 36(4.5%) 18(2.2%)
28(9.0%) 28(9.0%) 4(l.2%)
212(6.4%) 3(0.09%) 206(6.4%) 43(1.3%) 3(0.09%) l4(0.4%)
20(6.l%) l(.3%) 19(5.8%) 12(3.3%)

 

73

 

Table 12. Continued.
Population type Number Methods
Reference Year Place and characteristics tested used
Webb 1971 D.C. Negroes-clinic ages
0-21 976 2 and 4
Standard 1972 D.C. Negro-children 708 4 and 5
TOTALS D.C. NEGROES 9503
Moran 1972 Danville Negro hospital
Va. patients 3822 2 and 5
TOTALS Virginia NEGROES 3822
Tomlinson 1941 W. Virginia Negro hospital
patients 275 7
TOTALS W. Virginia NEGROES 275
Mujamoto and
Korb 1927 St. Louis, Negro hospital
Mo. patients 300 1
Chernoff 1956 St. Louis, Negro hospital
Mo. patients 1000 2 and 4
Goldstein 1964 St. Louis, Negro hospital
Mo. patients 500 2
Minnich
, et 31, 1962 St. Louis, Negro newborns-
_"_’ Mo. cord bloods 449 2 and 4
TOTALS Missouri NEGROES 2249
Lawrence 1927 Nashville, Negro students
Tenn. and patients 100 1
Lawrence 1927 Nashville White students 100 1
Diggs gt g1. 1933 Memphis, Negroes from hosp., ‘
Tenn. school children 2539 1
and teachers
Adams 2; g1. 1953 Memphis, Negro maternity
Tenn. patients 2011 4

74

1

 

Overall % Percent Percent Percent Percent Percent Others

sickle cell SS AS AC SC AD

 

84(8.6%)
58(8.3%)
640(6.7%)

236(6.2%) 7(0.18%) 203(5.3%) 7(0.18%)
236(6.2%)

18(6.S%)

18(6.S%)

19(6.3%)

94(9.4%) 94(9.4%) 26(2.6%) 4(0.4%)

43(8.6%) 43(8.6%) 12(2.4%)

47(10.5%) 47(10.5%) 9(2.0%) 2(0.4%)

203(9.0%)

5(5.0%)
3(3.0%)

211(8.3%)

159(7.0%)

75

Table 12. Continued.

 

W
Number Methods

Population type

 

Reference Year Place and characteristics tested used
Adams g£_gl: 1953 Memphis, Tenn. Negro newborns 824 4
McCormick 1960 Memphis, and Negroes-clinic,
West Tenn. autopsy, TB and 2800 2 and 4
hosp. patients
McCormick 1965 Memphis, Tenn. Negro-Autopsies 3199 2 and 4
TOTALS Tennessee NEGROES 11473
Pollitzer
' 93.3l: 1959 Robson Co, N.C. Lumbee Indians 1332 2
Pollitzer Indian Sec., Indian triracial
g£_al. 1966 N.C. isolate 232 2
Pollitzer
g£_gl: 1966 Northeast, N.C. Non-Indian 145 2
Hansen-Preuss 1936 Durham, N.C. Negro hospital
patients 100 l
Chernoff and 1958 Durham, N.C. V.A. hosp. patients-
Weichselbaum non-Negroes 734 2
Chernoff and 1958 Durham, N.C. Negro hospital
Weichselbaum patients 390 2
TOTALS N. Carolina NEGROES 490
Pollitzer 1966 Walterboro,
g£_gl, S.C. Triracial Isolate 74 9
Johnson and
Townsend 1937 S.C. Negroes 719 8
Switzer and 1948 Charleston, Negro OB patients,
Fouche S.C. hosp. employees and 1000 1
patients
Switzer 1950 Charleston, Negro school chil-
S.C. dren and hosp. 3066 1

patients

76

 

Overall % Percent Percent Percent Percent Percent Others
sickle cell SS AS AC SC AD
9(1.l%)
277(9.9%) 19(0.7%) 254(9.l%) 60(2.1%) 4(0.14%) 1(0.04%) 4(0.l4%)
305(9.5%) 305(9.5%)
966(8.4%)
23(1.7%) 23(1.7%) 23(1.7%) 1(<0.01%)
4(1.7%) 4(l.7%) l3(5.6%)
l(0.7%) l(0.7%) 19(13.1%)
7(7.0%)
l(0.l3%) l(0.13%) l(0.l3%)
34(8.7%) l(0.25%) 33(8.5%) l(0.25%) 3(0.8%)
41(8.4%)
9(12.2%) 9(12.2%)
57(7.9%)
140(14%)

412(13.4%)

Table 12.

Continued.

 

77

—p

 

Population type Number Methods .
Reference Year Place and characteristics tested used 3
1.
Pollitzer 1966 James 15., '
lg; g1. S.C. Negroes 276 2
Pollitzer 1958 Costal S.C. Negroes-clinic 483 2
Boyle, g3 g1. 1968 Charleston, Negroes-randomly
S.C. selected from ages 775 2
35 or above
Ludvigsen and 1972 Greenville, Negroes-screening
Smith S.C. program 1878 2 and 5
TOTALS S. Carolina NEGROES 8197
Sydenstricker 1924 Augusta, Ga. Negroes 300 1
Sydenstricker 1924 Augusta, Ga. Negroes 1800 l ‘
C00per g3 g1. 1963 Southeast, Ga. Negroes 247 2 1
TOTALS Georgia NEGROES 2347
Diggs _5 g1. 1933 Gainesville, Negro school chil-
Fla. dren and teachers 674 1
Cotter and 1963 Gainesville, Negroes-prenatal
Prystowsky Fla. clinic 944 2
Pollitzer 1966 Hollywood, Seminoles-Indians 374 9
lg; g1. Fla.
TOTALS Florida NEGROES 1618
Thompson 1964 Mississippi Whites 1045 2
.8211.-
Thompson 1964 Mississippi "Americans" 429 2
91.1.9.1.-
Thompson 1964 Mississippi Negroes 1310 2
stal-
TOTALS Mississippi NEGROES 1310

78

I

Overall % Percent Percent Percent Percent Percent Others

 

 

 

sickle cell SS AS AC SC AD
S7(20.6%) 57(20.6%) 2(0.7%)

75(1S.S%) 2(0.4%) 73(15.l%) l4(3.1%)
114(14.7%) 1(0.13%) 113(14.6%) 17(2.2%)
138(7.4%) 1(0.05%) 130(6.9%) 8(0.43%)
993(12.1%)

l3(4.3%)

101(5.6%)

21(8.5%) 2(0.8%) 19(7.7%) 4(l.6%)
s-thal
l35(5.8%)

65(9.6%)

66(7.0%) 1(o.1%) 65(6.8%) 9(o.9%)
36(9.6%) 36(9.6%)

l3l(8.1%)
1(o.1%) 1(0.1%)

7(1.6%) 7(1.6%) 7(1.6%)

155(11.8%) 37(2.8%) 114(8.7%) 38(2.9%) 4(0.3%) 14(l.1%)

155(11.8%)

Table 12.

Continued.

 

79

 

t
L

Population type

 

 

Number Methods

 

Reference Year Place and characteristics tested used
Smith 1928 New Orleans, Negroes-random
La. patients 100 1
Ogden 1943 Louisiana White patients 910 8
Ogden 1943 Louisiana Negro patients 692 8
Beacham and 1950 New Orleans Negroes-Preg. 1200 4
Beacham La. females
Moffitt and 1959 Southern Whites 140 8
McDowell Louisiana
Moffitt and 1959 Southern Negroes 564 8
McDowell Louisiana
Cherrie 1963 Louisiana Negroes-college
students 134 2 and 4
Coulter 1965 New Orleans, Negro TB patients 220 8
La.
TOTALS Louisiana NEGROES 2910
Schneider 1954 Galveston, Negroes-Blood bank
Texas donors 505 2 and 4
Schneider 1956 Galveston, Negro hosp. patients 1550 2
Texas
Schneider 1956 Galveston, Negro clinic patients 2055 8
Texas
Bandau 1932 Houston, Negroes 150 9
Texas
Haynie et al. 1957 Houston, Negro hosp. patients 400 2
_—'F_' Texas
Killingsworth
and Wallace 1936 Dallas, Texas Whites 322 1
Killingsworth
and Wallace 1956 Dallas, Texas Mexicans 239 1

ll

80

 

Overall % Percent Percent Percent Percent Percent Others
sickle cell SS AS AC SC AD

 

5(5.0%)

0
45(6.5%)
100(8.3%)

l(0.7%) l(0.7%)

65(11.5%) 18(3.2%) 47(8.3%) 10(2.5%) 4(0.7%)

15(11.1%) 7(s.2%) 5(3.7%) 3(2.2%) 3(2.2%) 3(2.2%)

16(7.8%) 1(0.5%) 15(7.3%) 9(4.1%)

246(8.S%)

57(11.3%) 57(11.3%) 15(3.0%)

146(9.4%) 6(0.4%) 139(9.0%) 35(2.3%) 1(<o.1%)

203(9.9%) 6(0.3%) 196(9.9%) 50(2.4%) 1(0.os%)

10(6.7%)

42(10.5%) 5(1.3%) 36(9.0%) 6(1.5%) 1(o.25%) 1(0.25%)
0

3(1.2%)

81

 

 

 

 

 

Table 12. Continued.
Population type Number Method
Reference Year Place and characteristics tested used
Killingsworth Negroes-school chil-
and Wallace 1956 Dallas, Texas dren and hospital 1205 1
patients
Whalley _£_gl, 1963 Dallas, Texas Negro-preg. females 13835 2 and 4
Whalley et a1. 1964 Dallas, Texas Negro patients at
‘— “" OB clinic 3631 2 and 4
Long 1965 Dallas, Texas Negroes 1165 8
TOTALS Texas NEGROES 24496
Rucknagel 1957 Oklahoma Indians-Cherokees,
Caddoans, Muskhogeans 175 2
Cardoza 1957 Chicago, Ill. White-Hosp. patients 307 1
Cardoza 1957 Chicago, Ill. Negro-Hosp. patients 1263 l
Blanksma and 1966 Chicago, Ill. Negroes-Preg. Clinic 6360 2
Breen
TOTALS Illinois NEGROES 7930
Cooley and 1926 Detroit, Mi. Negroes-Hospital
Lee patients 400 1
Neel 1951 Detroit and Negro—Hosp. Patients 1000 l and 6
Ann Arbor, Mi.
Nalbandian, 1972 Detroit, Mi. Negro children
g£_gl, Hosp. patients 380 2 and 5
Nalbandian, 1971 Grand Rapids, Negro-School children 4465 2 and 5,
«:2. al.. Mi.
TOTALS Michigan NEGROES 6245
Whalley 1963 Cleveland, Negroes-Preg.
Ohio females 988 8
TOTALS Ohio NEGROES 988

 

82

W

Overall % Percent Percent Percent Percent Percent Others
sickle cell SS AS AC SC AD

 

65(5.3%)

1138(8.2%) 1138(8.2%)

475(13.1%) 475(13.1%)
85(7.3%) 7(0.6%) 78(6.7%) 40(3.1%)
2221(9.1%)

3(1.7%)
1(o.3%)
119(9.4%)
523(3.3%)

648(8.2%)

30(7.5%)
91(9.l%)

SSF
105(27.6%) 7(1.8%) 52(16.1) 7(1.8%) 39(10.3%)
266(6.0%) l(0.02%) 264(5.9%) 1(0.02%)'

492(7.9%)

79(8.0%)
79(8.0%)

 

83

Table 12. Continued.

 

W

 

Population type Number Methods
Reference Year Place and characteristics tested used
Rhatigan 1972 Witchita, Negro college
Kansas students 400 2 and 5
Rhatigan 1972 Witchita, Negroes-screening
Kansas program 1049 2 and 5
TOTALS Kansas NEGROES 1449
Loh 1971 Gary, Ind. Negro hosp. patients 2355 4 and 5
Bemis 1972 Milwaukee, Negro hosp. patients
Wise. and screening program 9881 2 and 5
Long 1967 Polk County, Negro hosp. patients approx.
Iowa 3000 9
Petrakis 1970 San Francisco, Negro clinic pa-
gp g1. Calif. tients and screening 4028 2
program
Binder and 1970 Ft. Bliss, Negro-military 1000 2

Jones Texas

Nalbandian, 1972 Ft. Knox, Ky. Military-Negro and 2939 2 and S

§L_gl. white

Fielding, 1972 U.S. Negro Job Corpsmen 11182 2
arm.

Fielding, 1972 U.S. Puerto Rican-Job 469 2
g3 g1. Corpsmen

Fielding, 1972 U.S. Mexican/Latin Am. 906 2
E£.El° Job Corpsmen

Fielding, 1972 U.S. White-Job Corpsmen 3426 2
e_ta_1.

Fielding, 1972 U.S. Caribbean(other than

gt gl. Puerto Rican Job 37 2

Corpsmen

84

 

Overall % Percent Percent Percent Percent Percent Others
sickle cell SS AS AC SC AD
28(7.0%) 28(7.0%)
approx. approx. approx.
10% 2(0.2%) 10%
132(9.l%)
202(8.6%)
931(9.4%) 29(0.3%) 880(8.8%) 22(0.2%)
267(8.9%) 12(0.4%) l71(5.7%) 12(0.4%) 3(0.1%)
351(8.7%) 351(8.7%)
75(7.5%) 1(0.l%) 73(7.3%) 1(0.1%)
s-thal
65(2.2%) 1(0.03%) 63(2.l%) 1(0.03%)
967(8.6%) 9(0.8%) 942(8.4%) 246(2.2%) 16(0.14%)
18(3.8%) 18(3.8%)
2(0.22%) 2(0.22%)
5(0.15%) 5(0.15%)
2(s.4%) 2(S.4%)

 

85

Table 12. Continued.

 

 

 

 

w W
Population type Number Methods
Reference Year Place and characteristics tested used
Fielding, 1972 U.S. American Indian, 398 2
et al. Oriental Job
Corpsmen
TOTALS U.S. NEGROES 133,457

Tested

86

 

Percent
AS

Percent Percent

AC

SC

_[

Percent
AD

Others

 

 

Overall % Percent
sickle cell SS

0

ll,387(8.5%)

# with Hgb S

 

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