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Pages 253-275

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From page 253... ... but with ~ variable component up to 20 per cent of the total of hemoglobin F.58 64, 6s <;nrP hr~m^~7`rctnilc ;nA;`r;` must have received ~ sickle cell gene from both parents, then, with certain very rare exceptions to be discussed later' both parents of a child with this type of sickle cell anemia must exhibit the sickling phenomenon. Tow, one of the appeals of genetics is that one can submit hypotheses to rather rigorous testing. Read the entire page →
From page 254... ... NON-SICKLE CELL TRAIT AMONG THE NONANEMIC SIBLINGS OF CHILDREN WITH SICKLE CELL ANEMIA, BOTH PARENTS KNOWN OR ASSUMED TO HAVE THE SICKLE CELL TRAIT. Author Number with s.c.t. Read the entire page →
From page 255... ... The modes in the case of Raper's data do not correspond with the values observed ir: the American Negroes, but this may be due to the different techniques employed. The role of the genetic mechanism responsible for this bimodality in the maintenance of the relatively high frequency of the sickle cell gene, a subject to be discussed later, is unknown. Read the entire page →
From page 256... ... to be discussed later, we feel that G is better designated a normal variant than an abnormal hemoglobin. The genetic basis of hemoglobin H appears to be somewhat different from that of the other abnormal hemoglobins discussed thus far. Read the entire page →
From page 257... ... ~ or several years it has been recognized that ~nd~~-iduals with thalassemia minor might, on moving boundary electrophoresis, exhibit a minor hemoglobin component with mobility slightly greater than hemoglobin A.7~ ~' 60 More recently, Kunkel and Wallenius,30 using "starch block" electrophoresis, have observed the regular occurrence of a minor hemoglobin component, now termed A`', in normal blood, which component is increased in thalassemia minor; this is apparently identical with the just-mentioned fast-moving shoulder seen in thalassemia minor with moving boundary eiectrophoresis. Here may be a "handle" which will make thalassemia minor somewhat easier to work with. Read the entire page →
From page 258... ... Most of the evidence suggesting non-allelism is supplied by the TABLE II A SUMMARY OF THE TYPES OF CHILDREN RESULTING FROM 1\IARRIAGES BETWEEN A l\.CRMAL INDIVIDUAL AND ONE WITH BOTH THE THALASSEMIA GENE AND THE GENE RESPONSIBLE F R HEMCGL~BIN S l l Children t Authors Ethnic background Tha, assemiasickle cell disea se Normal Thalassem~a Sickle cell Trait Silvestroni and Bianco, 195265 Powell, Rodarte, and Neel, 1950;'$3 Neel, Itano, and Lawrence, 19535-' Neel, 1951,4S kindred 60 Ceppellinili Italian (Italy) Read the entire page →
From page 259... ... A number of investigators have postulated that several more or even all of the genes responsible for the abnormal hemoglobins may fall into the S-C series of multiple alleles.24, 9' 45' 3~, 35 This opinion is based in part on the apparent absence of normal hemoglobin in persons heterozygous for two of these genes, as S-D. In the final analysis, however, these genetic relationships can only be established with certainty from the study of fertile marriages in which one of the marital partners is simultaneously heterozygous for two or more of the genes concerned. Read the entire page →
From page 260... ... Robinson, one of the co-authors, to compare the hemoglobin G in this family with that identified as G by Edington, Lehmann, and Schneider in 1955,19 with agreement in all essential respects.) The propositus for this kindred was a 28-year-old male of Italian extraction who appeared on clinical grounds to have sickle cell anemia. Read the entire page →
From page 261... ... GENETICS OF AB N:ORMAL HEMOGLOBINS�NEEL 261 FIG. 2.�Picture pedigree of a family in which hemoglobins S and G and thalassemia were encountered. Read the entire page →
From page 262... ... Bus marriage to a completely normal woman, III-4, has thus far resulted in one child whose hemoglobin on electrophoresis shows an AG pattern. The proper genetic interpretation of these findings would appear to be that III-3 has inherited the sickle cell gene from his father and the hemoglobin G gene from his mother, and has, in turn, transmitted the latter gene to his daughter. Read the entire page →
From page 263... ... There comes a time in the development of many genetic problems when a symbolic shorthand becomes a great aid to clarity of thought and brevity of expression. That time has arrived with respect to the abnormal hemoglobins. Read the entire page →
From page 264... ... In brief, it is suggested that the first locus to be recognized as associated with hemoglobin production be given the locus symbol Hbi. We now recognize three different genes which may occur at that locus, the normal gene, HERA, and the abnormal genes associated with the production of hemoglobins S and C, namely, Hats and Half. Read the entire page →
From page 265... ... In view of the apparent differences in amino acid composition between fetal and adult hemoglobin, and in view of the "template" concept of protein synthesis, the biochemical evidence would seem to favor the latter hypothesis, a point of view previously expressed by Itano,24 Singer, Singer, and Goldberg,70 and Huisman, Jonxis, and van der Schaaf.2~ This locus might be designated as Hb3, with the only gene thus far known for this locus being Hb3F. Biochemical Genetics and the Abnormal Hemoglobins. Read the entire page →
From page 266... ... alte.rations 1 1 they induce are not reflected in the phenotype as it is usually studied. It is conceivable that some amino acid substitutions in tI,e chains which comprise a hemoglobin molecule are not critical, in the sense of producing clinical effects of altering hemoglobin behavior by any of our current tests. Read the entire page →
From page 267... ... Since it is a well established tenet of genetics that mutation tends to be recurrent, in any consideration of the population genetics of the abnormal hemoglobins there immediately arises the question of the frequency with which mutation resulting in the hemoglobin genes is occurring. There are a good 'many complications to establishing unequivocally the fact that a mutation has occurred.77 Be that as it may, there are now in the literature a number of reports suggestive of mutation to the sickle cell gene.49' 77' 32 These involve for the most part the failure of a mother of a child with sickle cell anemia to exhibit the sickle cell trait or any other identifiable hemoglobin abnormality. Read the entire page →
From page 268... ... He postulates that the relatively recent spread of "slash and burn" agriculture through large parts of Africa has created an ecological situation favorable to an increased importance of the malaria parasite, and hence has lead to an extension of the conditions resulting in selection for the sickle cell gene. There is, then, something of a conflict in evidence, between findings indicating a sufficient mutation rate to account for numerous local origins of the sickle cell gene, and other findings suggesting that much of the present-day distribution of the sickle cell gene can be accc~unted for through relatively recent gene flow and increase with changing selective pressures, with the inference that mutation is extremely rare. Read the entire page →
From page 269... ... W., and Neel, J V.: A new inherited abnormality of hemoglobin and its interaction with sickle cell hemoglobin, Blood 6: 1240-1259, 1951. Read the entire page →
From page 270... ... B.: Distribution of parasites in the red cells of sickle cell trait carriers infected with Plasmodium falciparum, Tr. Read the entire page →
From page 271... ... I Their demonstration in sickle cell anemia and other hematologic disorders by means of alkali denaturation, Blood 6: 413~28, 1951. Read the entire page →
From page 272... ... This reminded me of the time when the biochemical genetics of ne2~rostora was still young and when enzymes were considered primary gene products, a concept which since then has been modified extensively. I wonder whether perhaps some caution is not also indicated if one regards hemoglobins as primary gene products. Read the entire page →
From page 273... ... Be that as it may, I am still inclined to the view that the amino acid sequence in a hemoglobin molecule reflects exactly the information carried in the genes. If two loci that segregate independently determine sequences in different parts of the molecule, the normal molecule would be an association product which contains both sequences. Read the entire page →
From page 274... ... Whether other factors than malaria pressure are of importance in maintaining a high f requency of the sickle cell gene is still an open question. This is the best that I think anyone can do at the present time. Read the entire page →
From page 275... ... Our assumption has been that some stress circumstance is necessary for hemoglobin H to become manifest, such a circ~mstance being thalassemia on the other side of the family in our recent occurrence and in the published instances. In the two early cases, we considered the possibility of the stress of age as an evocative circumstance for the fast hemoglobin production, provided that the genetic possibility is present. Read the entire page →

From page 253...

... but with ~ variable component up to 20 per cent of the total of hemoglobin F.58 64, 6s <;nrP hr~m^~7`rctnilc ;nA;`r;` must have received ~ sickle cell gene from both parents, then, with certain very rare exceptions to be discussed later' both parents of a child with this type of sickle cell anemia must exhibit the sickling phenomenon. Tow, one of the appeals of genetics is that one can submit hypotheses to rather rigorous testing.