Current Concepts of the Genetics of Thalassemia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75046/1/j.1749-6632.1965.tb54045.x.pd

DUPLICATION OF STRUCTURAL GENES FOR HEMOGLOBIN Α AND Β CHAINS IN MAN *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73379/1/j.1749-6632.1974.tb21868.x.pd

Immunological quantification of hemoglobins F and A2

Radial immunodiffusion techniques for hemoglobins F and A2 are described. Both techniques compare favorably with results obtained by alkali denaturation and cellulose acetate electrophoresis, respectively. Comparable results are obtained by immunoassay of hemoglobin solutions or lysed whole blood, obviating expensive equipment or washing red cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22409/1/0000859.pd

Transfer of small plasmid DNA fragments from polyacrylamide gels onto nitrocellulose paper

The incorporation into a 7% polyacrylamide gel of a nucleic acid-specific photochemical reagent 4,5',8-trimethylpsoralen at a concentration of 1 mg/dl of acrylamide solution improves both the sensitivity and the efficiency of the transfer of plasmid DNA fragments from the gel onto nitrocellulose filters. This improvement allows detection by blot hybridization of DNA fragments as small as 57 bp long.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25088/1/0000519.pd

The Thai variant and the distribution of alleles of 6-phosphogluconate dehydrogenase and the distribution of glucose 6-phosphate dehydrogenase deficiency in Thailand

The samples were taken from 3185 subjects from ten provinces throughout Thailand. In 1577 males the frequency of glucose 6-phosphate dehydrogenase deficiency was 11.98%. In the far south the gene frequency was 2.83%; in the remainder of the country the frequency did not vary significantly about a mean of 13.76%. The deficiency is of a severe type. The G6PD of all of the nondeficient individuals had the electrophoretic mobility of type B. The mean frequency of the A/B electrophoretic phenotype of 6-phosphogluconate dehydrogenase is 8.47%. The maximum frequency was in central and southern Thailand with a decline to the north and northeast. A variant form of 6-PGD, referred to as the Thai variant, has been found in which two additional electrophoretic components migrate anodally to the normal A band, confirming that the molecule is at least a dimer. The hypothesis is advanced that erythrocyte 6-PGD is determined by two genetic loci, only one of which is translated in leukocytes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44140/1/10528_2005_Article_BF01474765.pd

Highly sensitive and rapid gene mapping using miniaturized blot hybridization: application to prenatal diagnosis

We have developed a protocol for the preparation and analysis of amniocyte DNA which permits more sensitive and more rapid antenatal detection of sickle-cell anemia (SCA) than previously has been possible. After rapid extraction of DNA from amniotic cells, only 50 ng of MstII-digested DNA need be analyzed by mini-gel electrophoresis and hybridization detection to determine reliably the fetal genotype. Under these conditions, the entire gene-mapping procedure can be performed within 5 days. When larger amounts of DNA (> 500 ng) are analyzed, the minimal diagnosis time is reduced to 2 days. The resolution of restriction fragments on mini-gels is comparable to that obtained with larger gels. The 1.15-kb [beta]A and 1.35-kb [beta]S MstII fragments are well separated. The technique is useful whenever rapid and sensitive analysis of genomic DNA is desired.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24827/1/0000253.pd

Stability over time of hematological variables in 197 children with sickle cell anemia

One hundred ninety-seven children with sickle cell anemia were followed for 4 years at the Wayne State Comprehensive Sickle Cell Center to evaluate the stability of the hematological variables (Hb, Hct, RBC count, MCV, %HbF and %HBA 2 ) over time. The mean values of the hematological measurements taken during three separate 16-month intervals were used to represent an individual's values. The correlations of the hematological variables between intervals ranged from a low of 0.46 for %HBA 2 to a high of 0.91 for %HbF. Correlations that spanned two intervals (an average of 32 months) were of the same magnitude as those that spanned only one interval (an average of 16 months), suggesting that there was no decrease in the degree of stability of these variables as the time between measurements increased. The stability of the correlations between variables within intervals, and the stability of the coefficients of the first two principal components of the six hematological variables over time suggested that the relationships among variables were also stable. In a recent report [Odenheimer et al, 1983], we used the values of the six hematological variables collected at an individual's first visit to the sickle cell center to identify four hematologically distinct subgroups of children. In the current report, we found that as many as 83% of the individuals remained in the same subgroup in at least two of the three follow-up intervals, suggesting that the factors that contributed to this classification were the result of stable, rather than transient phenomena.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38236/1/1320180316_ftp.pd

Cord blood screening for hemoglobin disorders by high-performance liquid chromatography,

Ion-exchange high-performance liquid chromatography was employed as a screening method for abnormal hemoglobins in the newborn period. Samples of cord blood collected in EDTA tubes were used for this analysis. Hemolysates were injected onto 4.1 x 100-mm Synchropak ion-exchange columns using an automatic injector. Hemoglobin separation was carried out by means of a sodium acetate gradient. A total of 415 samples was analyzed. Hemoglobins A, F, and Bart's, as well as C or S when present, were separately eluted and quantitated using a 35-min gradient program. Four individuals with sickle cell disease, 26 with S or C trait, one with SC disease, and two others with alpha-chain variants were diagnosed with this method. The proportion of Bart's hemoglobin was greater than 1% in 33 individuals. The elution pattern was highly reproducible. The potential for complete automation and the ease with which quality control can be assured make this technique well suited for the detection of abnormal hemoglobins in the newborn period.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23944/1/0000191.pd

Rib infarcts and acute chest syndrome in sickle cell diseases

In the absence of evidence for pneumonia or pulmonary embolus, primary pulmonary infarction has been assumed to be the cause of the syndrome of chest pain, fever, and pulmonary infiltrate on chest X-ray that commonly complicates sickle cell anaemia. To find out whether the syndrome might be due to rib infarction, 99mTc-diphosphonate bone scans were done. In the eleven episodes thus investigated (10 patients) the scans showed segmental areas of increased radionuclide uptake in ribs, indicative of bone infarction. A possible sequence of events is that the rib infarcts are primary and cause bone pain, followed by soft tissue reaction, pleuritis, and splinting. The resultant hypoventilation leads to atelectasis and subsequent development of the radiographic changes of the acute chest syndrome. Prevention of hypoventilation and treatment of bone pain are important therapeutic goals.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29382/1/0000452.pd