A new RFLP detected with the anonymous single copy genomic clone L1.7 (D5S1).
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Biomedical subjects
Publications and source records attributed to E J Devor.
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The transmissibilities of 11 human craniofacial dimensions are estimated by path analysis based upon familial correlations obtained in four different populations. Estimates from both the individual populations and from pooled correlations indicate that the observed variation in craniofacial dimensions is determined by genetic and nongenetic factors in roughly equal measure (.45 less than t 2 less than .60). These results implicate the possibility of complex gene-environment and gene-gene interactions in the development of the size and shape of the head and face and call for more detailed familial studies of these traits. This additional complexity further suggests the need for caution in interpreting such metrical variation, especially from a diagnostic or classificatory viewpoint.
Data on 34 anthropometric measures from the Alexanderwohl Mennonite congregations of Kansas and Nebraska are presented. A factor analysis of these traits shows that body length and body width measures are distinct from each other as well as from measures of the head and face. Moreover, familial correlations estimated by maximum likelihood for all 34 traits tend to separate from each other along factor lines with correlations for body lengths being the highest and those for skinfolds and circumferences being the lowest. These results suggest the presence of various body "fields" which are under differing degrees of genetic and environmental control. We offer the term "functional multifactorial complex" as a means of referring to the joint genetic and environmental influences on these fields.
A study of the intergenerational transmissibilities of 34 anthropometric measures from the Alexanderwohl Mennonite congregations of Kansas and Nebraska is presented. Results presented tend to confirm the suggestion made previously by us (Devor et al., 1985) that patterns of transmissibility conform to a concept of "functional multifactorial complexes" operating in the body in a way analogous to the "field" concept of dental morphology.
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The method of commingling analysis is applied to distributions of six quantitative neuromuscular traits. Results show that only two of these traits may be described by the single normal distribution commonly associated with quantitative variables. The remaining four traits show significant skewness which is best accounted for by a mixture of three component distributions. The pattern of commingling found suggests the presence of a major (megaphenic) effect operating in these traits. Further, evidence is found which links the major effect in three of the four commingled traits to a single process which may be related to neurological control. The etiology of the major effect (i.e., whether genetic or environmental) cannot be determined from commingling analysis, but some suggestions are offered based upon the nature of the traits themselves and the major effects.
Familial phenotypic resemblance for six quantitative neuromuscular performance traits is analyzed by path analysis using data from the Mennonite community of Goessel, Kansas. Of the six traits only one, dominant hand strength, shows no evidence of parent-offspring transmission (t2 = 0.001) and only one, trunk flexibility, shows evidence of a high degree of transmissibility (t2 = 0.662). The four remaining traits display low to moderate levels of transmissibility (t2 = 0.073 to t2 = 0.245). A substantial residual sibling resemblance due to shared environmental effects is seen for all six traits. It is suggested that the high heritabilities found for many of these traits by other methods result from the inability of these methods to account for the shared nongenetic effects.
The families of 250 consecutive, unselected patients with Tourette syndrome (TS) were analyzed. If the parents had either motor or vocal tics, but not both, there was an increased risk of both TS and tics in the offspring. The mode of inheritance of the combined tic-Tourette trait was evaluated in both nuclear families and extended pedigrees. Complex segregation analysis was carried out allowing for possible contributions from both a major autosomal locus and multifactorial inheritance of variation in the background of each genotype. The most likely mode of inheritance was a major semidominant gene, Ts, with low heritability of the multifactorial background variation. This was true regardless of assumptions about the prevalence of the disorder. The hypothesis of strict multifactorial inheritance could not be rejected with nuclear family data alone. However, the hypothesis of no major gene effect was rejected using data on 3 generations for any estimate of lifetime risk less than 12 per 1,000 in the general population. A pure recessive major gene effect was also rejected. With a gene frequency of approximately .5%, the penetrance was estimated to be about 94% in abnormal Ts/Ts homozygotes, 50% in Ts/ts heterozygotes, and less than 0.3% in normal ts/ts homozygotes. More than two of every three cases are heterozygotes, and nearly all other cases are phenocopies or new mutations. This is the first demonstration by segregation analysis of a major gene in a human neuropsychiatric disorder with a frequency approaching 1% of the population.
A sample of 35 published pedigrees of Gilles de la Tourette syndrome is studied using complex segregation analysis with pointers. Results indicate the presence of a rare, semidominant, incompletely penetrant allele leading to affection. This result is consistent with that previously reported by Comings et al. on a larger, independent sample.
The population structure of Ramea Island, Newfoundland, is described using surname, marital migration, and serological data. Results presented indicate that Ramea is an open and heterogeneous population. It is shown, however, that this contemporary characterization has a time depth of only three decades and has resulted from a rapid population response to a single historical/economic event.
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Genetic data consisting of 14 red cell antigen groups and 11 serum and erythrocytic protein marker systems from four Eskimo populations of the Norton Sound area of Alaska are reported. The population structure of these four groups in analyzed both separately and within the larger context by comparison to 15 other circumpolar groups. These analyses reveal a good fit between genetic structure, geographic distribution, linguistic affiliation, and the ethnohistory of the region.
A subgroup of Athabascan Indians in Arizona and New Mexico was found to have an unusually high incidence of severe combined immunodeficiency, probably due to founder effect. Closed genetic pressures have limited their histocompatibility-antigen heterogeneity, enabling 3 patients to be grafted, 2 of them across HLA-B locus barriers.
Many studies report unusually high rates of gallbladder cancer among all American Indians and among Hispanic Americans in the Southwest and California. It has been suggested that there is a strong genetic component to the development of this cancer in American Indians and that the high rates among Hispanics are a result of genetic admixture with Indian groups. In this paper, we review the epidemiologic characteristics of gallbladder cancer in New Mexico's Hispanic population. We discuss the genetic study of the residents of the Abiquiu area of Rio Arriba County in northern New Mexico where the incidence of gallbladder cancer in white residents is significantly higher than that in any other county of the state. The Abiquiu population has a high degree of Indian ancestry, is genetically isolated, and shows close inbreeding. This combination has produced elevated frequencies of the allele or alleles predisposing to gallbladder cancer. Two familial aggregations of this disease, the first such aggregations to be reported, appear among these people.
An investigation of the mating structure of the rural Hispanic population of the village of abiquiu in northern New Mexico was carried out using village marriage registers. Marital movement and departure from random mating were analyzed by the distribution of birth places of marriage partners and by surname isonymy. The time periods studied were 1882 to 1910 and 1947 to 1977. The results of these analyses show marked marital isolation (median marital distances by birthplace of 11.5 and 20.0 miles, respectively) and a significant departure from random mating (F = 0.0556 and F = 0.0495, respectively). In each case the non-random component of the isonymy coeffient (Fn) greatly exceeds the random, or expected, component. Assortative mating for culture and proximity governed by the historical settlement pattern is indicated as the process producing these results. Isolation has begun to break down in recent years but as yet has had no great effect on the genetic structure of the Abiquiu population.
The rhesus macaque displays an extensive polymorphism at the transferrin locus. A principal components analysis describes the variance and covariance of alleles at the transferrin locus in eight widely dispersed sample populations. Using an eigenvectorial representation of the covariance matrix and systematically approximated geographical locations the distribution of populations and transferrin alleles is compared. Alleles with high variance prove to be the determining factor in the placement of populations in a "genetic map" and provide a means for interpreting the low congruence of genetics and geography found.
Concern with the frequency and patterning of the occurrence of midline neural-tube defects among contemporary human populations is widespread. These defects are, however, quite old and occur in unusually high numbers of prehistoric skeletons. A common explanation offered for such high incidence has been inbreeding among small, reproductively isolated populations. In a sample of 54 skeletons from the prehistoric south-western Indian site of Tijeras Pueblo in New Mexico, failure of neural-tube closure occurs in 10% of sacra recovered. While a more homogeneous genetic background and inbreeding may account for a portion of this elevated prevalence, the cause appears to lie with cultural-environmental factors. It is suggested that the aetiology of these conditions has become more complex in recent human history.
Family resemblance for normal pulmonary function as measured by forced vital capacity and one second forced expiration volume is assessed using a path analysis model which incorporates sex differences in transmissibility of the phenotype from parents to offspring as well as in the effect of a correlated shared-sibling environment. Application of this model, called XTAU, to familial correlations indicates that transmissible factors, which may be genetic or cultural, accounts for 20-30% of the variation in these measures. Further, a pronounced same-sex-specific effect of the sibling environment is indicated which enhanced the observed correlation between same-sex siblings and diminished the observed correlation between opposite-sex siblings. These results are consistent with findings of twin studies of pulmonary function indicating high heritability for both FVC and FEV1.0. In addition, the complex multifactorial model of family resemblance for normal pulmonary function is shown to have implications for specifying causal models of pulmonary disorders such as asthma, bronchitis, allergic rhinitis, and chronic obstructive pulmonary disease.