Genealogy reconstruction from short tandem repeat genotypes in an Amazonian population.

We have reconstructed partial genealogies in a sample of 44 SW Amazonian Rondonian Surui, in which 45 dinucleotide short tandem repeat polymorphisms had previously been typed. The genotypes of 488 pairs of individuals having an age difference of 13 or greater were compared, and parentage was excluded if a pair failed to share an allele at more than one locus. In order to test the power of this method, we computed the expected distribution of the number of exclusionary loci for such pairs of unrelated individuals, as well as that for individuals with different degrees of relatedness, and compared it to the observed distribution. We estimated that the pairs compared contained approximately 20% of individual pairs with a first-cousin relation or closer. A total of 25 pairs were identified as possible parent-child. In three instances, we could identify two or more children having a common parent; we computed a relatedness coefficient in order to establish whether the children were full or half sibs. The genealogies inferred show that instances of polygyny and polyandry (or, alternatively, serial mating), in addition to apparent monogamy, can be found among the Surui. The Surui sample can be used as a model for paleoanthropological populations, in which the determination of relatedness can provide further insights into the social structure of past populations. We estimate that, depending on the history of the populations and the degree of inbreeding, 10-20 highly informative nuclear loci should be typed in order to infer genealogies with acceptable confidence.

Strong balancing selection at HLA loci: evidence from segregation in South Amerindian families.

The genotypic proportions for major histocompatibility complex loci, HLA-A and HLA-B, of progeny in families in 23 South Amerindian tribes in which segregation for homozygotes and heterozygotes could occur are examined. Overall, there is a large deficiency of homozygotes compared with Mendelian expectations (for HLA-A, 114 observed and 155.50 expected and for HLA-B 110 observed and 144.75 expected), consistent with strong balancing selection favoring heterozygotes. There is no evidence that these deficiencies were associated with particular alleles or with the age of the individuals sampled. When these families were divided into four mating types, there was strong selection against homozygotes, averaging 0.462 for three of the mating types over the two loci. For the other mating type in which the female parent is homozygous and shares one allele with the heterozygous male parent, there was no evidence of selection against homozygotes. A theoretical model incorporating these findings surprisingly does not result in a stable polymorphism for two alleles but does result in an excess of heterozygotes and a minimum fitness at intermediate allele frequencies. However, for more than two alleles, balancing selection does occur and the model approaches the qualities of the symmetrical heterozygote advantage model as the number of alleles increases.

HLA and mate selection: no evidence in South Amerindians.

There have been reports of nonrandom mating (negative-assortative mating) or preference for individuals of different major histocompatibility complex (MHC) genotypes in both mice and humans. We have examined the association of HLA-A and HLA-B genotypes, both for each locus by itself and for two-locus genotypes, in mates of 194 couples from 11 South Amerindian tribes. The proportion of couples sampled averaged >50% of the total matings with progeny for 10 of the tribes. In nearly all cases, HLA-sharing proportions were very close to those expected from random mating, suggesting strong negative-assortative mating for MHC is not present in these South Amerindians.

Tracing prehistoric migrations by the viruses they carry: human T-cell lymphotropic viruses as markers of ethnic relationships.

Three reasons that HTLV-I and HTLV-II would not be expected to trace human migrations over extended time periods have been examined, and none has proven fatal to the theory. Transmission of the HTLVs (human T-cell lymphotropic viruses) in endemic settings highly depends on passage through breast milk, and this creates a pattern of distribution similar to that of mitochondrial DNA. The HTLVs probably evolve at variable rates, making the extent of sequence change a poor tool for dating human migrations. However, qualitative relationships between the sequence of human population separations and virus strain may be more regular. The uniqueness of viruses as markers of human relationship gives this method special value as a source of novel ideas regarding human movements and as independent confirmation of migration hypotheses that have been based on more conventional methods.

Evidence for balancing of KM, but not GM, alleles by heterotic advantage in South Amerinds.

Two KM alleles occur in 1075 South Amerinds of 14 tribes in approximately balanced and uniform frequency. However, the number of heterozygotes is 12.7% greater than expected by frequency analysis and 16.5% greater by segregation analysis. This excess is evident in children 0-4 years of age and may reflect either prenatal or early childhood selection. The frequencies of GM haplotypes were different, and quite uniformly so, in diverse tribes. Most GM heterozygotes can only be distinguished from GM 1,2,17 21 homozygotes by DNA or family relationship. No deficit of GM homozygotes was observed in 119 children in whom heterozygosis was determined by family. Thus, the KM polymorphism, like HLA, may be maintained by preferential survival of heterozygotes, but GM probably depends on another mechanism.

Random mating and selection in families against homozygotes for HLA in south Amerindians.

We have examined HLA-A and HLA-B in a large sample of families of South Amerindians for non-random mating and for Mendelian segregation in their progeny. The proportion of couples sampled for mating averaged over 50% of the total matings with progeny for 10 of the 11 tribes with 10 or more known matings. In nearly all cases, HLA-sharing proportions were very close to those expected from random mating, suggesting strong negative-assortative mating for MHC is not present in these South Amerindians. In progeny from these matings and others in 23 tribes, there was a large deficiency of homozygotes (excess of heterozygotes) compared with Mendelian expectations. In particular, there was a deficiency in all types of matings except when the female was a homozygote and the male shared one allele with her; the reciprocal mating showed no such deficiency. This non-reciprocity suggests the importance of some type of maternal-fetal interaction. A model to describe these results showed very surprising properties for two alleles: no change in allelic frequency like neutrality, an excess of heterozygotes like heterozygote advantage, and a minimum fitness at intermediate allelic frequency like heterozygote disadvantage. For three or more alleles, the model has the qualities of a traditional balancing selection model.

Twenty-five years of HTLV type II follow-up with a possible case of tropical spastic paraparesis in the Kayapo, a Brazilian Indian tribe.

A longitudinal study, spanning 25 years and great demographic and cultural change, found a persistently high prevalence of human T-lymphotropic virus type II (HTLV-II) in the Xikrin Kayapo Indians of Brazil. More than 10% of the children continue to develop immune reactions to the virus in infancy, a sharp increase in seroprevalence occurs between ages 15 and 30 years, and prevalence in older woman still approaches 100%. This suggests that the major modes of transmission (breast milk and sexual activity) have not changed. The demonstration of stable maintenance of HTLV-II in one ethnic group makes migration theories of its dispersal more plausible. However, the infection may not be a negligible burden on population survival: at least 1 of 62 persons followed until age 40 years died of possible tropical spastic paraparesis (TSP).

Endemicity and phylogeny of the human T cell lymphotropic virus type II subtype A from the Kayapo Indians of Brazil: evidence for limited regional dissemination.

Long terminal repeat (LTR)-based restriction fragment length polymorphism (RFLP) analysis of human T cell lymphotropic virus type II (HTLV-II) from 17 seropositive Kayapo Indians from Brazil showed that all 17 samples contained a unique HTLV-IIa subtype (A-II). Additional RFLP screening demonstrated the presence of this subtype in two of three Brazilian blood donors and a Mexican prostitute and her child. In contrast, 129 samples from blood donors and intravenous drug users (IDUs) from the United States, two Pueblo Indian samples, five samples from Norwegian IDUs, and two samples from blood donors from Denmark were all found to be a different HTLV-IIa subtype (A-III). Phylogenetic analysis of two Kayapo and one Mexican LTR sequences showed that they cluster with a subtype A-II sequence from a Brazilian blood donor and with sequences from two prostitutes from Ghana and Cameroon. These results demonstrate that infection with the A-II subtype is endemic among the Kayapo Amerindians, has disseminated to non-Indian populations in Brazil, and is also present in Mexico. Furthermore, the A-II subtype does not appear to represent an origin for the HTLV-IIa infection in urban areas of the United States and Europe. This study provides evidence that HTLV-IIa may be a Paleo-Indian subtype as previously suggested for HTLV-IIb.

Genetic variants of human T-lymphotrophic virus type II in American Indian groups.

The human T-lymphotropic virus type II (HTLV-II) is found in many New World Indian groups in North and South America and may have entered the New World from Asia with the earliest migration of ancestral Amerindians over 15,000 years ago. To characterize the phylogenetic relationships of HTLV-II strains infecting geographically diverse Indian populations, we used polymerase chain reaction to amplify HTLV-II sequences from lymphocytes of seropositive Amerindians from Brazil (Kraho, Kayapo, and Kaxuyana), Panama (Guaymi), and the United States (the Navajo and Pueblo tribes of the southwestern states and the Seminoles of Florida). Sequence analysis of a 780-base pair fragment (located between the env gene and the second exons of tax/rex) revealed that Amerindian viruses clustered in the same two genetic subtypes (IIa and IIb) previously identified for viruses from intravenous drug users. Most infected North and Central American Indians had subtype IIb, while HTLV-II infected members of three remote Amazonian tribes clustered as a distinct group within subtype IIa. These findings suggest that the ancestral Amerindians migrating to the New World brought at least two genetic subtypes, IIa and IIb. Because HTLV-II strains from Amazonian Indians form a distinct group within subtype HTLV-IIa, these Brazilian tribes are unlikely to be the source of IIa viruses in North American drug users. Finally, the near identity of viral sequences from geographically diverse populations indicate that HTLV-II is a very ancient virus of man.

Class I HLA antigens in two long-separated populations: Melanesians and South Amerinds.

Class I HLA antigens have been compared in 5,835 Melanesians of Papua New Guinea and 2,028 Amerindians of South America. The sample includes 50 PNGMel ethnolinguistic groups and 22 SAmInd groups. Both carry 15 serologically defined antigens and an undefined C allele. Except for A2 in Papua New Guinea and Cw1 in South America, these antigens are widely distributed in their respective populations. Nine (A2 and A24, B39, B60 and B62, and Cw1, Cw3, Cw4, and Cw7) are common to both. This commonality suggests that these two populations derive from an ancestral population with less polymorphism than modern East Asians. In both populations several theoretically possible haplotypes were absent, and other haplotypes were in positive disequilibrium in both. The parallels in disequilibria suggest that haplotypes are subject to selective forces acting on the level of allelic interaction. Based on three locus haplotype frequencies, the PNGMel groups form five clusters with internally typical linguistic and geographic characteristics and miscellaneous category, but SAmInd groups show no cluster.

HLA, Gm, and Km polymorphisms and immunity to infectious diseases in South Amerinds.

Isolated South Amerinds, a population at very high risk from infectious disease, mount good immune responses to pneumococcal polysaccharides, viral antigens and other immunogens. No unusual immunoglobulin allotype or HLA antigen, which might explain the high risk from infectious disease, was found among them. Responses are examined in relation to the immunogenetic markers that are most prevalent. Amerinds with Gm 1,2,17,21 responded less well than persons without this haplotype to 10 of 12 pneumococcal polysaccharides, and those who were homozygous at the HLA class I loci responded less well to viral antigens. However, these differences are not strong and there are few such findings relative to the number of possibilities examined. The most distinctive immunogenetic characteristic of these populations is their low level of polymorphism at all tested loci. Their susceptibility to infectious agents can be attributed to this genetic uniformity and a consequent ability of pathogens to adapt to the population.

Endemic transmission of HTLV type II among Kayapo Indians of Brazil.

Serological studies on 926 blood samples from 703 Brazilian Kayapo (Cayapo) Indians showed, by conventional definition of HTLV seropositivity, a 28% prevalence of human T lymphotropic virus (HTLV) infection, the highest yet reported. Immunoblot (WB) and SYNTH-EIA patterns indicate that the predominant infecting agent is type II. Of children under 15 years old, 12% were positive, and of persons over 60, more than 60%. Perinatal and heterosexual modes of transmission offer an adequate explanation of this incidence. Infection in infancy may include infection via breast milk from women other than the mother. Evidence of new infection in adults is apparent at an earlier age in women than in men. This pattern of antibody prevalence was not determined by cohort effects, as demonstrated by tests of serial specimens. Enzyme immunosorbent assay (EIA) absorbencies were not stable in the paired specimens: five serum pairs reverted and mean absorbencies declined over some age ranges. Many specimens with relatively high, but less than positive, EIA results were positive by immunoblot (WB). This suggests that the standard EIA end point does not identify all infected persons. If the WB alone indicates positivity, 47% of the whole population, and more than 80% of the older age groups, are infected with HTLV-II.

Further blood genetic studies on Amazonian diversity--data from four Indian groups.

Information related to 31 protein genetic systems was obtained for 307 individuals affiliated with the Cinta Larga, Karitiana, Surui and Kararaô Indians of northern Brazil. In terms of genetic distances the Cinta Larga showed more similarities with the Karitiana (both are Tupi-speaking tribes), while at a more distant level the Surui clustered with the Kararaô. The latter, a Cayapo subgroup, showed a completely different genetic constitution from the other subgroups of this same tribe. Both the Kararaô and Karitiana are small, remnant populations, and their gene pools have presumably been severely affected by random and founder effects. These results were incorporated with those of 25 other Amazonian Indian tribes, and analysis by two multivariate techniques confirmed a previously observed geographical dichotomy, suggesting either that the Amazon river constitutes a barrier to north-south gene flow or that latitudinally different past migrations entered the region from the west.

Reasons for failure of genetic classifications of South Amerind populations.

Previous attempts to classify South American Indian tribes according to genetic characteristics have failed to yield a hierarchical system of relationships. This can be explained by the facts that (1) tribal populations did not evolve through sequential fissions but through frequent fusions of groups with diverse histories and (2) allele frequencies have been held at nearly common values by intertribal migration or balancing selection. A valid model must allow for fusion and mixed populations as well as for fission; factor analysis or newer methods of fuzzy mathematics permit this. The effects of migration and balancing can be made more manageable by partitioning them according to the limited time periods recorded by haplotypes. An initial attempt using factor analysis and HLA haplotype data on 19 rain forest tribes revealed two overlapping clusters that are largely but not neatly separated by the lower Amazon River. Several tribes, especially in the west, were excluded from these clusters.

Studies of three Amerindian populations using nuclear DNA polymorphisms.

Three Amerindian populations, two from Rondônia, Brazil (Karitiana and Rondônia Suruí), and one from Campeche, Mexico (Mayan), were typed for up to 30 nuclear restriction fragment length polymorphisms (RFLPs). Heterozygosities, both observed and expected, were compared with those of Europeans. Average heterozygosity is reduced among these Amerindians (relative to that of Europeans) by 7.0% (Mayan) to 27.1% (Karitiana). This amount of heterozygosity in the nuclear DNA is nevertheless high enough that it is unlikely that there was a severe or prolonged bottleneck.

Blood genetic systems in four Amazonian tribes.

Data on 31 genetic systems were obtained for 421 individuals belonging to the Arara, Araweté, Mundurucu, and Jamamadi tribes of northern Brazil. The Jamamadi depart farthest, and the Mundurucu least, from South American Indian averages. These data are analyzed together with those of 24 other Amazonian groups. Genetic distances and corresponding dendrograms indicate a cluster of 14 related tribes living north of the Amazon river. These genetic results show only a modest correlation with linguistic and geographic relationships among these groups.

Isoelectric focusing studies in Brazilian Indians--uncovering variation of ORM, AHSG and IF.

Allele frequencies for the orosomucoid 1 (ORM1), orosomucoid 2 (ORM2), alpha-2-HS-glycoprotein (AHSG) and complement component I (IF) loci were studied in 393 individuals of three Brazilian Indian tribes. In the ORM1 locus only two alleles were observed among the Urubu-Kaapor, while five were found among the Pacaás Novos. The frequency of ORM1*1 was similar in these two tribes (0.734 and 0.715, respectively) but departed more markedly among the Parakanã (0.870). Variation for ORM2 locus was found among the Pacaás Novos only, with ORM2*3 being observed in just three individuals. A new variant (AHSG*PN) was found in the AHSG system. Frequency for AHSG*1 was unexpectedly low in the three tribes, especially, among the Pacaás Novos, where the prevalence (0.145) is the lowest considering other data reported thus far. For IF locus, variability was also restricted to only one trible (Urubu-Kaapor) and attributed to a new polymorphic allele, IF* A3.

Durability of passive measles antibody in Jamaican children.

Measles antibody titres were determined by haemagglutination inhibition and by neutralization in 221 sets of serum collected from delivering mothers, umbilical cords, and infants when about six months of age. Radio-immunoassay was also used to measure antibody in 120 sera. Total IgG concentration was determined in the infant sera. All mothers had measles antibody and the mean titre was high. At the time of birth, measles antibody had been further concentrated in the infant. Nevertheless, many children lost protective titres before six months of age. The rate of loss was correlated with the infant's total serum IgG so that high IgG levels at six months correlated with rapid loss of measles-specific antibody. It is suggested that in homes where sanitation is poor, antibody is made to many agents at an early age. To maintain physiological balance, homeostatic mechanisms then increase the rate of catabolism of all IgG, including that passively acquired. In keeping with its stage of sanitary development, vaccination in Jamaica can profitably be given earlier than in the United States, but it must be later than in many African countries.