Search PubMed⌕ Search

Biomedical subjects

S Karlin

Publications and source records attributed to S Karlin.

At least 145 records · Page 8Linked to original sources
PubMed1981

Genetic analysis of the Stanford LRC family study data. I. Structured exploratory data analysis of height and weight measurements.

A new methodology for determining mode for inheritance of continuously distributed traits in nuclear families, structured exploratory data analysis (SEDA), is described and applied to height and weight measurements. The family data were collected as part of the Lipid Research Clinic's collaborative study (LRC) and consists of first degree relatives of Stanford University employees who were selected either as a 2% random sample or were identified through a high lipid value. The variables are all standardized using three methods of age and sex adjustment based on two reference populations. The analysis and interpretations are based on the following statistics and indices: 1) the major gene index (MGI (alpha); 2) two measures of correlations between the midparental value and offspring (MPCC); and 3) the offspring between parent functions (OBP (beta). Consistent with a number of other studies, the results support that height shows multifactorial inheritance while height is principally under the influence of non-genetic environmental factors. In contrast to the random families, the male children of the probands who were selected due to their high lipid values exhibit height measurements which appear to involve environmental components or some major gene concomitants. The difference between the random and high lipid families is supported by all three statistical methods.

Adolescent↗
PubMed1981

Genetic analysis of the Stanford LRC family study data. II. Structured exploratory data analysis of lipids and lipoproteins.

A newly developed methodology for the assessment of mode of inheritance of continuously distributed traits in nuclear families, structured exploratory data analysis (SEDA), is applied to lipid and lipoprotein measurements. Specifically, three measures: the major gene index (MGI), the pairwise midparental correlation coefficient (MPCC), and the offspring between parents (OBP) curves are used to determine whether these trait expressions are more major gene, sporadic, or multifactorial relative to one another. Triglycerides and the closely-related VLDL-cholesterol measurement appears to be transmitted through some major components. HDL-cholesterol measurements are more consistent with some degree of multifactorial transmission or a major gene model with additive allelic effects and similar allele frequencies. The results for LDL-cholesterol suggest a modicum of major gene influences. The composite total cholesterol measurement appears to be under multifactorial transmission but of lower order than height. Younger families who were selected through a parent with high lipid levels exhibit some major gene influences which do not appear in the older families. Several possible explanations are proposed for this difference.

Cholesterol↗
PubMed1981

Structured exploratory data analysis (SEDA) for determining mode of inheritance of quantitative traits. I. Simulation studies on the effect of background distributions.

We examine through simulations the effectiveness of a new methodology to help distinguish among monogenic, multifactorial, and sporadic trait transmission from parents to offspring in nuclear family data sets. The major gene index (MGI), which compares the deviation of the offspring from the midparental value with a function of the individual deviations between parents and offspring, aids in the discrimination of multifactorial from sporadic and monogenic models. In contrast with other methodologies, the ability of the MGI to separate multifactorial, monogenic, and sporadic models improves with increased skewness in the trait distribution. The midparental correlation coefficient serves as a further guide for indicating mode of inheritance. A new class of techniques, the offspring between parents function (OBP), is introduced that provides a more sensitive tool to help in assessing mode of transmission through the analysis of the level, shape, and undulation characteristics of the curves. Four data examples are used to illustrate the methodology: erythrocyte catechol-O-methyltransferase (COMT) activity, height, weight, and triglyceride measurements. Height appears largely multifactorial, and weight appears to be mostly sporadic, while COMT and triglyceride measurements suggest the presence of some major gene influences.

Genetics↗
PubMed1981

structured exploratory data analysis (SEDA) for determining mode of inheritance of quantitative traits. II. simulation studies on the effect of ascertaining families through high-valued probands.

An understanding of the effect of selecting families through a high-valued proband on the major gene index (MGI), the offspring between parents function (OBP), and the pairwise midparental correlation coefficient (MPCC) is developed. It is shown that the interpretations of these statistics must be carefully modified to adjust for the biases created by the selection criteria. Computer simulations are used to examine sporadic, multifactorial, and major gene models, under moderate (85%) and extreme (95%) proband selection. Additional insights may be acquired into the nature of mode of inheritance by comparing and contrasting selected and unselected of populations.

Computers↗
PubMed1980

The effects of increased phenotypic variance on the evolutionary outcomes of generalized major-gene models.

The study of generalized major-gene models has been extended to accommodate selective, assortative mating mechanisms. In this formulation the consequences of amplified phenotypic variance on the major gene frequency are investigated. It is shown that the rate of approach to the equilibrium state is slowed under attenuated assortative mating tendencies and/or with increased environmental noise. Also, an increased phenotypic variance induces more skewness in the nature of the gene frequencies, i.e. a less 'central' polymorphic expression. Where strong positive assortative mating occurs, a population fixation state results. Negative assortment generally facilitates the stability of a 'central' polymorphism.

Alleles↗
PubMed1979

Representation of Nonepistatic selection models and analysis of multilocus Hardy-Weinberg Equilibrium configurations.

The paper develops conditions for the existence and the stability of central equilibria emanating from selection recombination interaction with generalized nonepistatic selection forms operating in multilocus multiallele systems. The selection structure admits a natural representation as simple sums of Kronecker products based on a common set of marginal selection components. A flexible parametrization of the recombination process is introduced leading to a canonical derivation of the transformation equations connecting gamete frequency states over successive generations. Conditions for the existence and stability of multilocus Hardy-Weinberg (H.W.) type equilibria are elaborated for the classical nonepistatic models (multiplicative and additive viability effects across loci) as well as for generalized nonepistatic selection expressions. It is established that the range of recombination distributions maintaining a stable H.W. polymorphic equilibrium is confined to loose linkage in the pure multiplicative case, but is not restricted in the additive model. In the bisexual case we ascertain for the generalized nonepistatic model the stability conditions of a common H.W polymorphism.

Alleles↗
PubMed1979

Principles of polymorphism and epistasis for multilocus systems.

The nature of stable equilibrium configurations is described for general nonepistatic and generalized symmetric viability regimes in multilocus systems under conditions of tight and loose linkage. The influence of epistasis and symmetry can be better understood in terms of these standards. A dichotomy in the nature of stable polymorphisms emerges. More recombination, bisexuality, and multideme interactions facilitate the establishment of central type polymorphisms.

Journal Article↗