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J V Neel

Publications and source records attributed to J V Neel.

At least 127 records · Page 7Linked to original sources
PubMed1982

Separation of allelic variants by two-dimensional electrophoresis.

The resolving power of two-dimensional (2-D) gel electrophoresis has been tested using 17 allele products at five loci. Standard O'Farrell gels could separate 13 of these isozymes. The addition of a second pH gradient made it possible to separate all but one of the variant proteins. These results indicate that 2-D gel electrophoresis can resolve more than 90% of variants originally detected by one-dimensional (1-D) electrophoresis. The implications of these results for the low estimates of average heterozygosity obtained in surveys using 2-D gel electrophoresis are discussed.

Alleles↗
PubMed1982

Two-dimensional gel electrophoresis of cell proteins in childhood leukemia, with silver staining: a preliminary report.

We have investigated the potential of two-dimensional electrophoresis for identifying differences in protein patterns between acute lymphocytic (ALL) and acute myelogenous leukemia (AML). We studied blood cells directly isolated from seven children with non-T, non-B ALL and five with AML. Solubilized proteins were electrophoresed with the ISO-DALT system and made visible by silver staining. More than 800 spots were routinely detected in individual gels. Patterns for multiple runs of the same sample were indistinguishable. Most of the prominent spots were present in gels from all 12 of the individuals studied. However, substantial variability in spot intensity was observed, even among patients in the same group. Five spots were consistently present in gels of all the AML patient, and either completely absent or substantially decreased in ALL gels. Three other spots were present in ALL but not AML gels. We conclude that this may be a useful tool for characterizing leukemic cells.

Blood Proteins↗
PubMed1982

Two-dimensional electrophoretic analysis of erythrocyte membranes.

In an effort to maximize the amount of genetic information that can be extracted from a blood sample, we investigated the use of two-dimensional polyacrylamide-gel electrophoresis (PAGE) to resolve the protein constituents of the erythrocyte membrane. Lyophilized membranes were dissolved in various concentrations of urea, NP-40 detergent, and mercaptoethanol and subjected to two-dimensional PAGE by a modification of the O'Farrell procedure, with use of the ISO-DALT apparatus. More than 600 spots were visible in silver-stained gels under conditions that excluded specific cytoskeleton protein components, including spectrin and actin. The reproducibility of the pattern depended highly on the precise composition of the solubilization mixture. Poor resolution was observed in the presence of actin and other proteins of high molecular mass (spectrin bands 1 and 2) when we used high urea concentrations that solubilized the entire erythrocyte membrane. The large number of polypeptides observed could not be attributed to proteolysis, because addition of proteolytic inhibitors to the membrane wash solutions did not alter the pattern on the gel. The pattern also did not appear to include erythrocyte cytosol proteins because, except for globin, none of five purified erythrocyte lysate proteins was visible in the erythrocyte membrane gels. We conclude that two-dimensional electrophoresis provides a powerful tool for the study of non-cytoskeletal erythrocyte membrane proteins.

Blood Proteins↗
PubMed1982

Computer programs for adapting two-dimensional gels to the study of mutation.

We are attempting to adapt the two-dimensional polyacrylamide gel technology to the search for mutations that after the electrophoretic mobility of proteins. These events are expected to have a frequency on the order of 10(-6). To this end, programs that run on the CytocomputerTM are being developed for comparing the pattern of the gel derived from a child's blood sample with those of the gels of corresponding samples from its parents. We anticipate examining thousands of such trios. Programs are described that perform background normalization, noise filtering, spot detection, gel registration, and, finally, compare the father/mother/child gel trios for the presence of unique protein moieties in the child that are consistent with a mutational event.

Adult↗
PubMed1982

Contribution of familial factors to the occurrence of cancer before old age in twin veterans.

In an earlier report, we evaluated familial factors in deaths from all causes before age 62 among the 31,848 white male twin veterans who were followed during 1946-1978 through the National Academy of Sciences-National Research Council Twin Registry. We now report data for this group on twin concordances and heritabilities of cancer recorded on the death certificate as an underlying or associated cause. The study subjects have a mortality from cancer 0.88 times, and one from all causes 0.84 times, that of U.S. white males [12], but this is very similar to the mortality of other U.S. veterans [9]. Among 11,350 monozygotic (MZ) and 14,450 dizygotic (DZ) individuals in twin pairs alive on January 1, 1946, 1,162 MZ and 1,646 DZ individuals died before January 1, 1979. Cancer was diagnosed for 223 MZ and 323 DZ twins as an underlying or associated cause of death. Among the latter were 176 MZ and 274 DZ pairs with the only death in the pair a cancer death, 10 MZ and eight DZ pairs concordant for cancer, and 12 MZ and 14 DZ pairs in which the first death in the pair from cancer was followed by death of the other twin from another cause. When account is taken of the three MZ and two DZ pairs concordant for lung cancer, most likely related to cigarette smoking, the twin cancer death concordance rates are very low, and they are not appreciably different between the two zygosity groups. Genetic factors may be important in some specific forms of cancer. However, these data suggest that genetic factors and early familial environment, generally shared by twin-pair members, do not contribute much to mortality from most cancers between 30 and 60 years of age.

Adult↗
PubMed1981

Genetic effects of the atomic bombs: a reappraisal.

Data are presented on four indicators of genetic effects from studies of children born to survivors of the atomic bombings of Hiroshima and Nagasaki. The indicators are frequency of untoward pregnancy outcomes (stillbirth, major congenital defect, death during the first postnatal weak); occurrence of death in live-born children, through an average of life expectancy of 17 years; frequency of children with sex chromosome aneuploidy; and frequency of children with mutation resulting in an eletrophoretic variant. In no instance is there a statistically significant effect of parental exposure; but for all indicators the observed effect is in the direction suggested by the hypothesis that genetic damage resulted from the exposure. On the basis of assumptions concerning the contribution that spontaneous mutation in the preceding generation makes to the indicators in question, it is possible to estimate the genetic doubling dose for radiation for the first three indicators (the data base is still too small for the fourth). The average of these estimates is 156 rems. This is some four times higher than the results from experimental studies on the mouse with comparable radiation sources, which have been the principal guide to the presumed human sensitivities. The relevance of these data in setting permissible limits for human exposures is discussed briefly.

Chromosome Aberrations↗
PubMed1981

Familial factors in early deaths: twins followed 30 years to ages 51-61 in 1978.

Subjects in the National Academy of Sciences-National Research Council Twin Registry of 31,848 male twin veterans were followed for mortality from 1 January 1946, or from the date of entry into military service if that was later, to 31 December 1978. During this time 3,573 deaths occurred among them, 837 due to trauma and 2,712 due to disease. Mortality from all causes for the entire follow-up period was 10.2% among 11,350 monozygotic (MZ) twins and 11.4% among 14,450 dizygotic (DZ) twins. Mortality of veterans is known to be favorable compared to U.S. males. Among U.S. males of the same ages as the two respective twin zygosity groups, a mortality of 13.9% would have been expected during this time period. Observed mortality from trauma was 2.3% for MZ twins and 2.5% for DZ twins, with 3.0% expected in either group. Observed mortality from all disease was 7.9% for MZ twins and 8.8% for DZ twins, with 10.9% expected in either group. For total mortality, the case twin concordance rates, based on individual deaths, were 28.2% among MZ twins and 17.7% among DZ twins. For trauma, respectively by zygosity, these concordance rates were 6.9% and 3.9%. In this sample, familial factors appear to be of little consequence in trauma deaths. For all disease the concordance rates were 30.1% and 17.4%. Estimating heritability of liability to death from disease, as proposed by Edwards (1969), provides values of h2 = r = 0.51 for MZ twins, h2 = 2r = 0.48 for DZ twins, and h2 = 2(rMZ-rDZ) = 0.54 using data for the two zygosity groups combined.

Adult↗
PubMed1981

Is there a difference among human populations in the rate with which mutation produces electrophoretic variants?

Data are summarized that suggest that tropical-zone/tribal/nonindustrialized populations have higher frequencies of certain types of protein variants than temperate-zone/civilized/industrial populations, and it is demonstrated that these differences are not an artifact produced by the contagious type of sampling used with respect to tribal populations. Evidence is reviewed that suggests that a possible explanation of this difference is higher mutation rates in the tribal populations studied.

Alleles↗
PubMed1981

Frequency of thermostability variants: estimation of total "rare" variant frequency in human populations.

Eight erythrocyte enzymes were examined for thermostability in an unselected sample of 100 newborn infants. Three thermolabile variants, one each of lactate dehydrogenase, glucosephosphate isomerase, and glucose-6-phosphate dehydrogenase, were identified, none of which was detectable as a variant by standard electrophoretic techniques. All were inherited. This frequency of 3.8 heritable thermostabiliy variants per 1000 determinations is to be compared with a frequency of electrophoretically detectable variants of 1.1 per 1000 determinations, a frequency of 2.4 enzyme-deficiency variants per 1000 determinations, and a frequency of 1.1 hypo/hyperactive enzyme-activity variants per 1000 determinations in this human newborn population. The total measured frequency of individuals with rare enzyme deficiency or electrophoretic or thermostability (or both) variants at these loci is 8.3 per 1000 determinations. A similar distribution and frequency is seen when the comparison is limited to the seven loci studied by all techniques. It is clear that not all of the electrophoretic and thermostability variants present in the population are detected by the techniques used in this study. Accordingly, it is estimated that the true frequency of carriers of a rare variant for each of these enzyme-coding loci averages greater than 10/1000. Some implications of these frequencies for human disease are discussed.

Adult↗
PubMed1981

The impact of random and lineal fission of the genetic divergence of small human groups: a case study among the Yanomama.

Most of the genetic divergence that currently separates populations of Homo sapiens must have arisen during that long period when the local village (or band) was the basic unit of biological evolution. Studies of tribally intact Amerindian groups exhibiting such small-group organization have demonstrated marked genetic divergence between nearby villages. Some of this genetic radiation can be attributed to the effects of random genetic drift over time within these small demes. Some of it, however, might be better ascribed to the consequences of nonrandom genetic assortment at the time of village fission, a recurring event for such groups. Even random genetic assortment at the time of fission would lead to some genetic divergence, due to the finite size of the parent gene pool. We term the genetic consequences of random assortment the random fission effect. Routinely, village fission occurs along family lines, leading to even greater genetic divergence between the daughter villages. We use the term lineal fission effect to describe the genetic consequences of nonrandom assortment and contrast these results with those derived from random assortment--A formal treatment of random and lineal fission effects is developed, first for the single-locus case, then for the multiple-locus extension. Using this formulation, three Yanomama fission events were examined. Fission in the Yanomama often involves a great deal of mutual hostility between the two factions, so that subsequent gene flow between the two daughter villages is minimal. The first two examples are typical of the Yanomama behavior norm, and are accompanied by a minimum of subsequent gene flow between the daughter villages. In these two cases, the observed divergence values are very large and are also very unlikely under random fission. The lineal fission effect is pronounced. The net impact of lineal fission is to reduce the effective size of the village at the time of fission by a factor of four, relative to expectation from random fission. The third example, however, involved an unusually amicable split of a village, followed by free genetic exchange between the fission products. This "friendly fission" yields an observed divergence value not much in excess of the expectation from random fission.--The long-term consequences of such fission bottlenecks in effective population size are discussed for both intra- and inter-tribal genetic diversity. It appears that the rate of genetic divergence for tribal and subtribal groups may have been somewhat greater than would be expected from classical drift arguments.

Female↗
PubMed1981

Hormonal adaptation to the stresses imposed upon sodium balance by pregnancy and lactation in the Yanomama Indians, a culture without salt.

The Yanomama Indians of northern Brazil and southern Venezuela have been identified as a "no-salt" culture. In this study, data were obtained to determine in this population the adjustments of sodium-related hormones to the stresses imposed upon sodium balance by pregnancy and prolonged lactation. Controls against the possibility that findings in the Yanomama were ethnic rather than dietary were provided by similar observations in the Guaymi Indians of Panama, who have free access to salt. Urinary concentrations of sodium were approximately 1 mEq/l in male and female Yanomama, with 24-hour excretion rates in the males averaging 1 mEq, similar to our prior observation. The pregnant Yanomama had exceeding high urinary concentrations of aldosterone. These were associated with higher plasma renin activities and serum aldosterone concentrations than in all other subjects. Although pregnant Guaymi had elevations of serum and urinary aldosterone, these were significantly lower (p < 0.001) than those of the Yanomama. Prolonged lactation in the Yanomama was associated with elevation of plasma renin activity and serum and urinary aldosterone concentration compared with the Guaymi, but were not higher than those in nonlactating Yanomama females. The findings suggest that pregnancy in a salt-poor environment is associated with an exaggerated augmentation of hormonal responses that enhance positive sodium balance.

Adult↗
PubMed1981

Assigning a probability for paternity in apparent cases of mutation.

Any direct estimator of mutation in a human population is subject to error due to nonpaternity. This paper deals with the quantification of this error by producing, under certain assumptions, the probability for paternity. In addition, a new direct estimator of the mutation rate is introduced.

Alleles↗