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J V Neel

Publications and source records attributed to J V Neel.

At least 145 records · Page 8Linked to original sources
PubMed1980

Rate of spontaneous mutation at human loci encoding protein structure.

The techniques of electrophoresis were used in a search for evidence of mutation affecting protein structure, the indicators being hemoglobin and a set of serum proteins and erythrocyte enzymes. Among 94,796 locus tests on Amerindians from Central and South America, there was no evidence for mutation. Among 105,649 locus tests on newborn infants in Ann Arbor, Michigan, there was also no evidence for mutation. We have previously failed to encounter any mutations in a series of 208,196 locus tests involving Japanese children [Neel, J. V., Satoh, C., Hamilton, H. B., Otake, M., Goriki, K., Kageoka, T., Fugita, M., Neriishi, S & Asakawa,J. (1980) Proc. Natl. Acad. Sci. USA 77, 4221-4225], and H. Harris, D. A. Hopkinson, and E. B. Robson [(1974) Ann. Hum. Genet. 37, 237-253] found no mutations in 113,478 locus tests on inhabitants of the United Kingdom. This failure to demonstrate any mutations of this type in a total of 522,119 locus tests excludes, at the 95% level of probability, a mutation rate greater than 0.6 X 10(-5)/locus per generation in this combination of populations.

Blood Proteins↗
PubMed1980

Search for mutations affecting protein structure in children of atomic bomb survivors: preliminary report.

A total of 289,868 locus tests, based on 28 different protein phenotypes and using one-dimensional electrophoresis to detect variant proteins, has yielded one probable mutation in the offspring of "proximally exposed" parents, who received an estimated average gonadal exposure of 31 to 39 rem in the atomic bombings of Hiroshima and Nagasaki. There were no mutations in 208,196 locus tests involving children of "distally exposed" parents, who had essentially no radiation exposure.

Dose-Response Relationship, Radiation↗
PubMed1980

Genetic studies on the Ticuna, an enigmatic tribe of Central Amazonas.

The Ticuna are an Amerindian tribe of Central Amazonas, a key location in theories of the peopling of eastern South America. The results of typing some 1760 members of the tribe with respect to 37 different genetic systems are reported, as are the results of HLA typings on a subsample of 129 persons. Salient findings include the following. (1) Except for a high frequency of LMs allele and an unusual combination of HLA allele frequencies, there are no notable findings with respect to the commonly studied polymorphic systems. A multivariate treatment of six of the most commonly studied genetic polymorphisms accords the Ticuna an 'average' position among Amerindian tribes. (2) There is much less intervillage heterogenicity than usually encountered in Amerindian tribes; this is attributed to recent high rates of intervillage migration due to religious developments. (3) A thus-far unique polymorphism of ACP1 was identified, the responsible allele having a frequency of 0.111. (4) In proportion to the size of the tribe, there was a relative paucity of 'private' genetic variants, the ACP1 allele being the only one. This discrepancy is attributed to a relatively recent numerical expansion of the tribe; effective population size over the past several thousand years is thought to have been well below what present numbers would suggest. (5) The thesis is again advanced that 'private variants' (alleles not occurring as polymorphisms of wide distribution) are more common in Amerindian than in Caucasian or Japanese populations.

Alleles↗
PubMed1980

Variants of red cell enzymes found in Japanese of Hiroshima and Nagasaki.

In the course of our search for possible genetic effects of radiation among the children of A-bomb survivors in Hiroshima and Nagasaki, we have obtained considerable electrophoretic data which clearly illustrate some of the genetic characteristics of the populations of both cities, which characteristics, however, have no relationship with radiation exposure of the parents. The frequencies of variants of phosphoglucomutase1 (PGM1) and glucose phosphate isomerase (GPI) were observed to be significantly higher in Nagasaki than in Hiroshima. As the difference in the frequencies of transferrin variants between two cities are also significant, it is apparent that the populations of the two cities are genetically different with respect to variation in certain protein systems.

Child↗
PubMed1980

Epidemiologic studies among Amerindian populations of Amazonia. III. Intestinal parasitoses in newly contacted and acculturating villages.

The prevalences of intestinal parasites among the residents of three South American Indian villages in the process of acculturation were compared with those found in earlier unpublished surveys in two newly contracted village.s Although one individual in an acculturating village harbored 11 different intestinal parasites, in general the average number of different parasitic species carried per person was somewhat higher in the newly contacted villages. Helminth egg counts, performed on direct smears of each specimen from one newly contacted village, were low. There were no sex-associated differences in prevalences. The overall prevalences, unadjusted for age, were among the highest recorded for Amerindians. No Taenia species were present. Balantidium coli was present in two acculturating villages, concomitant with the beginning of agricultural practices which include raising swine. No cases of moderate or severe protein-calorie malnutrition was observed in any of the villages during the surveys. These limited data provide a baseline for future comparisons and, perhaps, a glimpse into the past.

Acculturation↗
PubMed1979

Electrophoretic variants in three Amerindian tribes: the Baniwa, Kanamari, and Central Pano of western Brazil.

Data are presented on electrophoretic variants of 25 polypeptides found in the blood serum and erythrocytes, in 812 individuals from three Amerindian tribes, the Pano, the Baniwa, and the Kanamari. Two "private polymorphisms" were encountered, of PEPB in the Pano and CAII in the Baniwa. A single example of a different PEPB variant was encountered in the Baniwa, and two possible examples of an unstable variant of HGB A2 in the Kanamari. In addition, the well-known A variant of ACP1, the Duarte variant of GALT, the 2 variant of Hp and the 2 variant of PGM1 occurred in polymorphic proportions in all three tribes, and the TFDChi variant was present as a polymorphism in the Baniwa. These data have recently been incorporated into a treatment which concludes that the eight electrophoretically-defined "private polymorphisms" thus far encountered in Amerindian tribes can be explained by a mutation pressure of 0.7 x 10(-5)/locus/generation on the assumption of neutrality of the phenotypes in question (Neel and Thompson, '78).

Asian People↗
PubMed1979

Hepatitis--Bs antigen in an isolated Indian population of southern Venezuela: a family study.

A genetic analysis of the presence of HBsAg in a population of which 7.2% of the members were positive is presented. Though the ratios of carriers: non-carriers were generally in good agreement with expectation if the carrier state were determined by homozygosity for a single recessive gene, the two examples of mating most critical to a test of the hypothesis, carrier X carrier, yielded 2 normal children among 4 in one family, and one normal child, the only offspring, in the second family. Other investigators have reported similar findings. We conclude that the hypothesis of simple recessive inheritance cannot be sustained.

Adolescent↗
PubMed1979

Epidemiologic studies among Amerindian populations of Amazonia. II. Prepvalence of Mansonella ozzardi.

The prevalence of microfilaremia among Indians in 13 Amazon Indian villages was determined by examining Giemsa-stained peripheral blood smears and preparations from peripheral blood lymphocyte cultures. Mansonella ozzardi was the only species found in the 601 persons tested. Prevalence was highly village-specific, ranging from 0% in four villages to as high as 93% among persons aged 10 years and older in others. Comparisons of the two methods showed that the concentration effect of the peripheral blood lymphocyte culture preparations allowed the detection of a greater number of microfilaria-positive persons, especially women and children with lower levels of parasitemia.

Adolescent↗
PubMed1979

Epidemiologic studies among Amerindian populations of Amazônia. I. Pyoderma: prevalence and associated pathogens.

Pyoderma was studied among a representative sample of the residents of four remote Amerindian villages, Amazonas State, Brazil, during July-August 1976. The overall prevalence among the 775 inhabitants examined was 11%, with little intervillage variation. When the attack rates for the entire sample population were calculated by 5-year age intervals, the 0- to 4-year-olds had the highest rate, 31%. The highest prevalence, 38%, was found among 3-year-olds. Attack rates were not apparently related to sex. Cultures which were taken from representative pyoderma lesions from people in the four survey villages and from three additional villages were studied by a modified delayed culture technique for recovery of gram-positive pathogens from silica-gel desiccated swabs. Group A and group G B-hemolytic streptococci, coagulase positive Staphylococcus aureus, and Corynebacterium diphtheriae were isolated. Group A S. pyogenes was most commonly found, occasionally as the sole pathogenic species. No nephritogenic M-types were found, although most isolates were not M-typable. The T-types found corresponded to those previously reported as being pyoderma-associated. Most pyoderma-associated C. diphtheriae isolates were non-toxigenic. Biotypes gravis and mitis were equally represented.

Adolescent↗
PubMed1978

The immunoglobulin allotypes (Gm and Km) of twelve Indian tribes of Central and South America.

The Gm and Km immunoglobulin allotypes are presented, for the first time, for six South American Indian tribes (Baniwa, Kanamari, Kraho, Makiritare, Panoa, and Ticuna) and one Central American tribe (Guaymi). Additional allotype information is presented for five previously reported South American tribes (Cayapo, Piaroa, Trio, Xavante and Yanomama). The distributions of the Gm and Km allotypes among all the tribal populations tested to date are reviewed and evidence is presented for the presence of a north (high)-south(low) cline in Km frequency. The wave theory of the populating of the South American continent was tested by an examination of the distribution of six alleles (Gmax;g, Gma;b0,3,t,Dia,Rx,TFDChi, and 6PGDC), absent in some populations but with polymorphic proportions in others. The present, limited, data failed to confirm the theory.

Alleles↗
PubMed1978

Indirect estimates of mutation rates in tribal Amerindians.

Three different formulations have been used to estimate the average rate/locus/generation with which mutation results in electrophoretically detectable variants of 28 proteins in 12 tribal Amerindian populations. All methods are indirect--i.e., they assume a reasonable approximation to equilibrium between mutation and loss of mutants from the population--and are based on the further assumption that the biochemical traits under consideration are essentially neutral in their phenotypic effects. Despite the fact that the methods draw on somewhat different aspects of the available data, there is satisfactory agreement between them, the average of the three estimates being 1.6 X 10(-5)/locus/generation. This average does not encompass mutation that does not result in a change in electrophoretic mobility or that results in loss of enzyme activity. It is noteworthy that this estimate is in satisfactory agreement with a recent estimate by Neel and Thompson [Neel, J. V. & Thompson, E. A. (1978) Proc. Natl. Acad. Sci. USA 75, 1904--1908] of the mutation pressure necessary to maintain the number of "private" genetic polymorphisms being encountered in Amerindian tribes, if selection is not a factor.

Genetic Variation↗
PubMed1978

Probability of founder effect in a tribal population.

When an unusually high frequency of an allele is encountered in a population, "founder effect" is often invoked as an explanation. As usually used, the term implies the disproportionate increase through chance (rather than selection) of an allele contributed to the population by a particular ancestor. While genetic theory leaves no doubt this is a possible explanation, problems arise when we try to determine how likely this explanation is for any specific finding in any specific, finite population, i.e., just how rare is this rare event? In this communication we consider the question in the context of Amerindian tribal populations, deriving specific probabilities under defined conditions. Our interest in the question has been whetted by the finding to date of some eight possible examples of a founder effect in studies of twelve different tribes.

Gene Frequency↗
PubMed1978

Founder effect and number of private polymorphisms observed in Amerindian tribes.

In studies extending over the past dozen years, we have observed eight examples of "private" genetic polymorphisms in 12 Amerindian tribes surveyed for electrophoretic variants of an average of 25 proteins. Each of these is presumed to trace to a single mutation. In a preceding communication [Thompson, E.A. & Neel, J.V. (1978) Proc. Natl. Acad. Sci. USA 75, 1442-1445] the statistical theory was developed for estimating the likelihood of such a founder effect in a tribal population of this type. In this paper that theory is applied to the distribution defined by these eight variants. It is demonstrated that on the assumption that the phenotypes in question are selectively neutral, such findings are most compatible with a mutation rate of 7 X 10(-6)/locus per generation. This figure applies only to variants that can be detected by the electrophoretic technique.

Alleles↗
PubMed1978

The frequency in Japanese of genetic variants of 22 proteins. IV. Acid phosphatase, NADP-isocitrate dehydrogenase, peptidase A, peptidase B and phosphohexose isomerase.

This paper presents the results of an electrophoretic survey of approximately 4000 individuals from Hiroshima and Nagasaki for four erythrocyte enzymes: isocitrate dehydrogenase, peptidase A, peptidase B, and phosphohexose isomerase. Also reported are the results for erythrocyte acid phosphatase for a subset of these individuals. The frequencies for the ACPA1 and ACPB1 alleles of the ACP1 locus are in agreement with previously reported results from Japanese populations. Rare variants of ICDS, PEPA, PEPB and PHI occur with frequencies varying from 0.25 to 7.2 per 1000 determinations. The relatively high frequency of the PHI 4HIR1 variant and some unusual features involving the effect of reducing agent on the electrophoretic pattern behaviour of some of the rare PHI variants detected during this study are discussed.

Acid Phosphatase↗
PubMed1978

Mutation and disease in man.

Efforts to evaluate the burden of genetic disease maintained by mutation pressure are reviewed. Various individuals and committees have suggested that approximately 1800 per 100,000 liveborn infants will ultimately exhibit clearly defined disease due to chromosomal or point mutation. Direct estimates of human chromosomal and point mutation now permit the identification of about 370 per 100,000 liveborn infants with defect due to mutation in the preceding generation. Recent technical advances permit the study of mutation to shift to the protein level. In Amerindians, mutations resulting in electrophoretic variants of a series of proteins of the blood serum and erythrocyte occur at at rate of 1.6 x 10(-5)/locus/generation. While it is debatable what proportion of electrophoretic variants result in impaired health as heterozgotes or homozgotes in man, we are increasingly aware of disease due to an absence of enzyme or receptor protein due to homozygosity for "null" alleles. A conservative calculation of the possible impact of these "null" mutations on health proceeds as follows: if the rate of mutation to electrophoretic variants in man is only 1.0 x 10(-5)/locus/generation, and if in man the ratio of nulls to electrophoretic variants is only 2:1 rather than 5:1 of Drosophila, then null mutants with respect to protein should be 2.0 x 10(-5)/locus/generation. There are perhaps 5,000 proteins in man whose absence can lead to disease. It is clear we are just beginning to recognize a class of mutations whose impact on health in toto may exceed the commonly visualized gross phenotypic abnormalities. However, many of the conceptuses homozygous for these null mutations may be eliminated in utero and not come to clinical attention.

Animals↗