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Mutation is an intrinsic property of genes and has provided the variability that we value as a characteristic of human populations as well as the variability that was necessary for evolution to occur. Nevertheless, an increase in mutation rate is almost universally regarded as undesirable. The likelihood that a random change in a gene will be beneficial to the host is small. The likelihood that it will be detrimental is much larger. There is much argument as to the proportion of genes that truly are neutral, but these are of no special concern to the present discussion. When a detrimental mutation occurs, it is expressed ultimately as failure of a zygote to develop, as abortion, as overt disease, or as reduced fertility. The expression may be immediate or delayed, depending on the degree of dominance of the mutalion. The social consequences of these different outcomes are different, much more so than the genetic consequences. A genetic death is failure to survive and reproduce, whether that failure be due to early death (as in Tay-Sachs disease) or to reduced fertility in an otherwise healthy person. Such detrimental genes are removed eventually from the population through natural selection—rapidly if the mutant allele is expressed in the heterozygote, much more slowly if the allele is completely recessive. Eventually an equilibrium is reached, with the number of mutant alleles eliminated by selection equal to the number produced by mutation. In the case of recessive alleles, many generations are required to establish a new equilibrium.

The major impact of an increase in genetic damage will be expressed as an increase in autosomal dominant and X-linked traits as well as chromosomal disorders. The present incidence of dominant traits has been estimated as 1% of live births, but recent data from British Columbia indicate the true value in that population may be an order of magnitude lower. These estimates are important if one measures the damage in terms of doubling dose. Neither the average mutation rate nor the number of loci capable of mutating to dominant detrimental form is known. Mutations that cause sterility or early embryonic loss are determental in the Darwinian sense but have little impact on society. Mutations that are more fit biologically may be a heavy burden to society if the affected persons require medical or institutional care. Since exposure to some mutagens is unavoidable, these factors must ultimately be included in a cost-benefit analysis.

A peptide difference has been found in the neutral-band (pH 6.4) regions of tryptic digests of human transferrins C and DChi. The peptide has the composition Asp-Ser-Ala-Arg. Therefore, this peptide is proposed as the 2TDChi b peptide, the result of the replacement of histidine by arginine in the Tf C peptide.

This is the fourth paper in a series on the distribution of blood groups among Indians of South America. It reports the findings on the Indians of Chile and the Polynesians of Chile's Easter Island. Blood specimens were procured from the following putatively pure Indians and unmixed Polynesians: 44 Alacaluf of Puerto Eden, Isla Wellington, 141 Mapuche (Araucanian) of Lonquimay, Malleco Province, 80 Atacamenos of Antofagasta Province, and 45 Polynesians of Easter Island. These 310 samples were tested for blood factors in the A-B-O, M-N-S-s, P, Rh-Hr, Lutheran, K-k, Lewis, Duffy, Kidd and Diego systems, and for the Wright (Wra) agglutinogen. Serum samples were tested for haptoglobins and transferrins. Hemolysates prepared from the blood clots were tested for hemoglobin types. The results are presented as phenotype incidences and calculated gene frequencies in appropriate tables. Locations of the populations from which blood samples were procured are shown on two maps. The high frequencies for the O gene usually reported for South American Indians obtain in putatively pure Chilean Indians but A1 is high in Easter Island Polynesians. In both Indians and Polynesians M, s, R1 (CDe), R2 (cDE), Lub, k, LeH, and Fya gene frequencies are high and B, N, S, Mia, Vw, Ro (cDe), r (cde), Lua, K, Le1, Fyb, and Wra (Ca) are low or absent. The Diego (Di) gene is present in the Mapuche and Atacamenos but absent in the Alacaluf and Polynesians. Hp1 gene frequencies were determined only in the Alacaluf and Atacamenos, in which they are 0.48 and 0.67 respectively. Transferrins were determined for the Alacaluf and Atacamenos Indians and all were classified as Tf C. All Chilean Indian and Polynesian specimens were tested electrophoretically for hemoglobin types and all contained only hemoglobin (A) as a major component.

Blood specimens from putatively pure Maya and Kekchi Indians in British Honduras; Bribri, Boruca, Cabecar and Terraba in Costa Rica; and San Blas Cuna, Choco and Guaymi in Panama have been tested for haptoglobins, transferrins and hemoglobin types, and the phenotype incidences and frequencies of genes controlling these serum proteins have been reported. Hp1 gene frequencies resemble generally those previously reported for Indians but the frequency of 0.197 for Hp1 among the Bribri of Costa Rica is the lowest re-ported for any aboriginal population in Middle America. The distribution of transferrins varies appreciably among these different popula-tions, the range being similar to those reported for other Middle Ameican tribes (Mat-son et al., '63). Nearly all 1,107 hemolysates tested had only type A hemoglobin. Hemoglobin type AS was found in two of 67 Terraba. These two specimens also tested R2r and R0r respec-tively for Rh genotypes, suggesting foreign admixture, since both R0 and r genes are extremely rare or absent in American Indians. Hemoglobin AS was observed also in five (two of whom were brothers) of 153 Guaymi Indians in Panama. One homozy-gous S type was found also among the Guyami. Two AS were present in 198 Samples of blood from the San Blas Cuna.

Peptide analyses have been carried out for chymotryptic digests of transferrin C and transferrin D(1). There is a difference in one peptide, and amino acid analyses indicate that an aspartic acid residue in transferrin C is replaced probably by a glycine residue in transferrin D(1).

To Mendel has often been attributed the good luck or good judgment of choosing for study traits that were clearly alternative characters and that were free of environmental influence. Galton, on the other hand, studied characteristics that were complex and that often had the potential for alteration by the environment, so-called multifactorial traits. The Galtonian approach, although it uses ever more sophisticated statistical and computational tools, has provided little insight into the mode of action of individual genes. It has, of course, been useful in plant and animal breeding experiments to study the contributions of both genetic and environmental variation and, as we have heard at this symposium, may help us to estimate inherited risk.

The subject of monitoring human populations for mutation has been much discussed in recent years and, I am pleased to say, some progress has been made in developing techniques and in implementing programs. Both the techniques and the programs are still very limited, and this review must still give more attention to possibilities than to existing programs.

Blood samples were procured from the following populations of putatively pure Indians in Bolivia: 503 Aymara from the Altiplano and Yungas, 30 Chama, 11 Tacana, 14 Chacobo, 109 Itonama, 67 More, and 27 Siriono from the Beni and lowland rainforest. Erythrocytes from these 761 specimens were tested for antigens in the A-B-O, M-N-S-s, P, Rh-Hr, Lutheran, Kell-Cellano, Lewis, Duffy, Kidd, and Diego systems, and for the Wright agglutinogen. The serum samples were tested for haptoglobins and transferrins; and hemolysates were prepared and examined for hemoglobin types. Results of these tests are presented as phenotypes and calculated gene frequencies on appropriate tables. A map is included to show the locations of the populations from which blood samples were obtained. Frequencies are generally high for the O gene, it being the only gene of the ABO system which appears in the Chama, Chacobo and Siriono. The presence of A1, A2 or B genes in the Bolivian Indians is interpreted as being most probably of caucasoid introduction. Excepting the Siriono the frequencies are high for M and low for N genes as is usual for Amerinds, the M gene being the only one detected in the Chama. The s gene frequency in high and the S low except in the small isolated Chacobo population in which S gene frequency is extremely high for Amerinds. Inbreeding and perhaps genetic drift in this small isolate may account for this aberrancy from normal. The Bolivian specimens presented the high frequencies for genes R1 (CDe) and R2 (cDE) and the low frequencies for genes r (cde) and R0 (cDe) usually observed in American Indians. The Lua factor was observed in only one of 120 Aymara at Santa Fe in the Yungas. The Lua factor, when observed in Amerinds, suggests foreign introduction of the responsible gene. Fya gene frequencies are consistently high and excepting the Aymara and Chama so also are Jka frequencies. Frequencies for the Diego (Dia) factor vary from 3.70% in 27 Siriono to 73.33% in 30 Chama. No K, Mia, Vw or Wra antigens were demonstrable in the Indian blood samples from Bolivia. Phenotypes and calculated gene frequencies for haptoglobins and transferrins are presented. All Bolivian Indian bloods tested electrophoretically contained only hemoglobin (A) as a major component.

This paper reports the results of tests made for hereditary antigens in blood samples procured from Indians in northern Brazil. Specimens were procured from 423 putatively full-blood persons of the following tribes: in the province of Roraima from 261 Macuxi, 48 Uaica, 27 Xirixano, 10 Uapixana, 9 Cacarapai and 9 Paramiteri; in Para from 21 Assurini; and in Amapa from 38 Galibi. Erythrocyte samples were tested for factors in the A-B-O, M-N-S-s, P, Rh-Hr, Lutheran, Kell-Cellano, Lewis, Duffy, Kidd and Diego systems. Serum samples were tested for haptoglobins and transferrins. Hemolysates, prepared from whole blood, were tested for hemoglobin types. The results are presented on appropriate tables as number and per cent of phenotypes for the various blood group anigens and their calculated gene frequencies. Locations from which blood samples were procured are listed in the tables and shown on a map (fig. 1). All the 423 samples except one Macuxi belonged to group O. The Uaica tribe had a low frequency for M (0.534). All others showed the high frequency usually observed in Amerinds. The s allele was high in all except the Galibi in which the frequency was (0.500). Frequencies for P2 was higher than for P1 in all except the Assurini and Galibi, theirs was high for P1 (1.00) and low for P2 (0.00). The frequencies for R1 (CDe) and R2 (cDE) were high and all others in the Rh-Hr system were low or absent. All specimens were positive for Cellano (k) and negative for Kell (K). There was a complete absence of Lewis (Le1), excepting in the Uaica and Xirixano in which populations Fya allele frequencies were higher than 0.500. The distribution of the Jk (a+) phenotype and corresponding ellele frequencies varied widely in Brazilian Indians as did those for Diego (a+). The haptoglobin Hp1 allele frequencies were in essential agreement with those reported elsewhere for Indians in South America, and all transferrins determined were classified as Tf C. All samples tested for homoglobin types contained homoglobin (A) as a major component, but five members of the Galibi tribe possessed hemoglobin (S) as well.

Summary Haptoglobin types have been determined by starch gel electrophoresis of blood from five populations. The gene frequencies obtained for allele Hp1 were as follows: American whites, 043; American Negroes, 0.59; African Negroes, 0.72; Apaches, 0.59; and Asiatic Indians, 0.18. In tribes of the Ivory Coast and Liberia, there was a suggestion of a cline which parallels that for haemoglobin S. Evidence is presented that the condition of ahaptoglobinemia is under genetic control but not by a gene allelic to the Hp1-Hp2 series. The importance of the ahaptoglobinemic individuals for genetic studies and the possibility of selection in the maintenance of the genetic polymorphism are discussed. The authors wish to acknowledge the excellent assistance of Alojzia Sandor, who carried out the electrophoretic separations.

This paper reports the distribution of blood groups, A-B-H secretors, haptoglobins, transferrins and hemoglobin types among Indians of the Gila River Valley in Arizona. Specimens were procured from the following putative full-bloods: 909 Pima, 37 Papago, and 124 Maricopa; and from the following known mixed-bloods: Pima-Papago 134, Pima-Maricopa 26, Pima-Other Indian 41, Pima-Caucasian 33. These 1304 samples were tested for factors in the A-B-O, M-N-S-s, P, Rh-Hr, Lutheran, Kell-Cellano, Lewis, Duffy, Kidd and Diego blood group systems, and for additional blood factors (Wra), Doa, Vel, Yta, Coa, Gya, Sav, and L. W. Serum samples were tested for haptoglobins and transferrins. Hemolysates, prepared from whole blood, were tested for hemoglobin types. The results are presented on appropriate tables as number and per cent of phenotypes for the various blood group antigens and their calculated allele frequencies. Locations of the populations from which blood samples were procured are shown on a map (fig. 1). Tests made by earlier workers on the blood of Arizona Indians and related tribes are presented for comparison and discussed. The usual high frequencies for allele O reported in Amerinds was found among the putatively full-blood Gila Indians; the 124 Maricopa presented the maximum frequency of 1.000. High frequencies were reported generally for M, s, P1, R1 (CDe), R2 (cDE), k (100%) Fy, and Doa alleles. Low frequencies were reported for N, S, r (cde), R° (cDe), fy, Le1w and Dia (Pima only). There was a wide variation in frequencies for jk, and Hp1, and there were 17 Transferrin Tf B1C observed in 270 Pima samples tested. All the remaining were classified as Tf C except two Tf B;C from mixed-bloods. All samples tested for Vel, Yta, Coa, Sav, and Hemoglobin (A) showed the maximum frequency (1.000) for their genes. The following antigens were completely absent: Lua, Mia, Vw, Mta, p, Pk, ry (CdE), K, and Wra. The results of this study suggests that the Papago tribe presents fewer genes of non-Indian origin than the Pima, and the Maricopa least of the three populations.

Human transferrin D(1) obtained from an Australian aborigine was found to have the same substitution of glycine for aspartic acid in peptide 1C previously shown in transferrin D(1) from an American Negro. This finding is relevant to formation of distinct Australoid and African populations.

The relationship between the childhood and adult forms of schizophrenia has been discussed in a previous paper, 16 and the opinion was expressed that the two forms of the disease are probably the same basic process. This conclusion was based largely on the following two lines of evidence: 1. Bender 3 demonstrated in long-term follow-up studies that the majority of schizophrenic children become schizophrenic adults. 2. The basic psychopathology in adult and childhood schizophrenia as described by several workers is markedly similar. 5,14 Additional evidence is the demonstration by Kallmann and Roth 6 that schizophrenia occurs at approximately the same frequency in the immediate families of adult and "preadolescent" schizophrenics. In the search for metabolic abnormalities in schizophrenia, there are certain advantages to using children as research subjects. The chief advantages are as follows: 1. Since the disease is in its early stages, any metabolic

THE use of starch gels as a supporting matrix for electrophoresis was found by Smithies1 to result in much greater resolution of the serum globulins than can be achieved by the other media thus far employed. On the basis of differences in the behaviour of the α2 globulins he was able to divide the Caucasians whom he studied into three qualitatively different groups and obtained evidence that these groups were the result of a Mendelian two-allele system showing no dominance, Types I and IIB representing the two homozygotes and Type 11A the heterozygote2.

This publication results from a very ambitious project—the cataloguing of all known inherited traits of man. That Dr. McKusick achieved a large measure of success is a tribute to his ability to organize masses of material. In order to accomplish this, the information was stored in a computer, and the printout was photographed directly for publication. In a brief introduction, Dr. Mc-Kusick explains his nosological philosophy: "They are either thesamedisease, if they are based on the same mutation, or they aredifferentdiseases." [Italics his.] It is subsequently apparent that this is meant literally; detectably different alleles (eg, the hemoglobin variants) are each given a separate entry. The main part of the text consists of 2,487 entries, including preferred and alternate trait designations, principal features of the phenotype, and selected references. The first "catalog" lists autosomal dominant traits, the second autosomal recessives, and the third X-linked recessives. Entries