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I B Borecki

Publications and source records attributed to I B Borecki.

At least 73 records · Page 4Linked to original sources
PubMed1990

Sex-linked determinants for IgM?

Evidence for a sex-linked determinant of immunoglobulin M levels was sought using correlational and commingling analyses in a sample of 174 randomly selected nuclear families. While mean IgM levels in females were approximately 25% higher than that in males, the pattern of familial correlations did not follow the expectations under a sex-linked model, and there was no commingling in the distribution of IgM levels as expected when a trait is under the influence of a major gene.

Canada↗
PubMed1990

Commingling and segregation analysis of blood pressure in a French-Canadian population.

Commingling and segregation of age-sex-adjusted systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MBP) were examined in 1,560 individuals from 374 French-Canadian nuclear families. After correction for skewness, evidence in favor of two commingled distributions was found for SBP in the combined data (parents and offspring) and in parents, but not in offspring. Segregation analysis (using the computer program POINTER) suggested that a multifactorial contribution to all three phenotypes was greater in offspring than in parents, which could be the result of either polygenic or shared environmental components relevant to sibships, or both. Statistical evidence was found for a major effect on SBP. However, Mendelian transmission of the major effect was rejected, and no transmission of the major effect (equal tau's) was not. This is just the opposite to what would be expected if the major effect was due to a major gene, and it would ordinarily be considered as sufficient evidence to refute a major gene effect on SBP. However, the commingling in parents but not in offspring (who are all below 26 years of age), and the finding of equal transmission probabilities (nearly equal to 1), are compatible with an alternative interpretation. It is possible that there is a real major gene effect on SBP but that the genotype for elevated SBP has not yet expressed itself in the offspring as they have not yet gone through the risk period. Accordingly, this possibility needs to be evaluated further in additional studies involving older offspring.

Blood Pressure↗
PubMed1990

Combined segregation and linkage analysis of genetic hemochromatosis using affection status, serum iron, and HLA.

Characterizing the distribution of parameters of iron metabolism by hemochromatosis genotype remains an important goal vis-à-vis potential screening strategies to identify individuals at genetic risk, since a specific marker to detect the abnormal gene has not been identified as yet. In the present investigation, we analyze serum iron values in ascertained families using a method which incorporates both segregation of the clinical affection status and the HLA linkage information to identify the underlying genotypes. The analysis is performed using an extension of the model presented by Bonney et al., comprising regressive models for segregation analysis and the multipoint linkage strategy implemented in LINKAGE. The gene was found to be completely recessive with respect to both clinical manifestations and serum iron abnormalities, with significant differences in expression by sex. Clinical manifestations were present for all male homozygotes in this data set, suggesting that the recessive hemochromatosis genotype is fully penetrant at all ages in males. This was not the case for younger females. Significant genotype-specific age and sex effects were found for serum iron values. It is interesting that deletion of the HLA marker information did not affect our ability to resolve the genetic model when we analyzed a bivariate phenotype. This serves as a reminder that a search for relevant biological markers can be equally important in discerning the genetic etiology of a disease trait, as a search for linked genetic markers.

Age Factors↗
PubMed1989

Genetic hemochromatosis: distribution analysis of six laboratory measures of iron metabolism.

Six laboratory measures of iron metabolism were studied in a control sample, and a family sample was ascertained on the basis of probands with clinically diagnosed genetic hemochromatosis. The respective distribution of each variable evidenced a mixture of components, presumably arising from the segregation of an HLA-linked locus for hemochromatosis. There were significant differences in the distributional characteristics with respect to sex and genotype-specific variances. These aspects of the data have important implications for subsequent segregation and linkage analyses, which traditionally assume homoscedasticity and homogeneity of the genetic effect.

Deferoxamine↗
PubMed1989

Segregation of genetic hemochromatosis indexed by latent capacity of transferrin.

A genetic analysis of the segregation of hereditary hemochromatosis, indexed by the measurement of latent capacity of transferrin (LCAP), was undertaken in an ascertained sample of 147 pedigrees from Brittany, France. There were no mean differences by sex in the distribution of LCAP in the control sample, although in the family data there was a higher representation of males with low values than of females with low values, consistent with the higher proportion of affected males. The results of bivariate segregation analysis revealed no systematic evidence for heterozygous expression either in the biochemical domain of LCAP abnormalities or in increased liability to overt symptomatic disease. Joint consideration of the quantitative variable with hemochromatosis affection status allowed clear resolution of a recessive single-gene inheritance pattern in these families.

Adult↗
PubMed1988

Genetic factors influencing apolipoprotein AI and AII levels in a kindred with premature coronary heart disease.

A single 51-member kindred, ascertained on the basis of a normotriglyceridemic proband with depressed high-density lipoprotein cholesterol (HDL-C) and myocardial infarctions at ages 40 and 42, was studied with respect to quantitative variation in HDL-C and apolipoprotein (apo) AI and AII levels. The results of bivariate segregation analysis suggest that the etiology of depressed HDL-C involves one or possibly two major loci: one has a pleiotropic effect on apo AI and apo AII levels and, possibly another one that affects apo AI levels. Both the major loci were characterized as having a dominant allele leading to depression of the respective trait(s). In addition, analysis of the cosegregation of HDL-C and apo AI levels gave evidence of residual nonfamilial factors common to both traits, leading to a positive covariance between them. This could reflect the role of apo AI in the transformation of nascent HDL-C particles into mature ones via its cofactor activity to lecithin cholesterol acyltransferase. The proposed two-locus model represents one possible etiology for the heterogeneous disorder of hypoalphalipoproteinemia. This analysis of a single pedigree does not completely define the genetic mechanism, but it does illustrate a useful new analytic approach.

Apolipoprotein A-I↗
PubMed1987

Resolution of genetic and uterine environmental effects in a family study of new dermatoglyphic measure: sole pattern ridge counts.

The heritability of sole pattern ridge counts was examined in two family studies of endogamous castes from peninsular India. The phenotypes included ridge counts for each of the eight configurational areas separately, all areas combined, and only distal areas combined. Differences in heritability estimates were found between populations as well as among the individual configurational areas. Although some ridge counts do not show familial resemblance, others appear to be moderately heritable. Estimates of h2 range from 0.36 to 0.63 in one family series and from 0.22 to 0.51 in the other. In addition, significant uterine environmental effects were detected in one family series but not in the other.

Dermatoglyphics↗
PubMed1987

A family study of dermatoglyphic traits in India: segregation analysis of accessory palmar triradii and the atd angle.

Accessory triradii and the atd angle were examined via complex segregation analysis in order to evaluate possible genetic effects on these dermatoglyphic traits, measured in an endogamous Brahmin caste of peninsular India. The phenotypes considered included: presence of accessory palmar triradii a' and d', associated with the interdigital areas II and IV, respectively; presence of an accessory axial triradius tt' associated with the proximal margin of the palm; and an arctanh-transformation of the atd angle measurement. For all accessory triradii considered in the present investigation familial resemblance was evident. The most parsimonious model which could account for the observed resemblance was a multifactorial model that includes polygenic effects as well as transmissible environmental effects that are inherited in the same pattern as polygenes. Evidence of familial resemblance was also found for the arctanh-transformed atd angle, which could be attributed, initially, to both a major effect and a multifactorial component. Tests of transmission of a putative major gene were performed which yielded results consistent with Mendelian transmission, although an alternative test of no transmission of the major effect also fit the data. In light of these contrasting results we are precluded from accepting with confidence the notion of a major gene influence on the atd angle. We have concluded that the accessory triradii a', d', and tt', and the atd angle are influenced by multifactorial effects, including additive polygenes and possible environmental factors, such as intrauterine effects.

Dermatoglyphics↗
PubMed1987

Robustness of path analysis of family resemblance against deviations from multivariate normality.

Path analysis is one of several methods available for quantitative genetic analysis, providing for both tests of hypotheses and estimates of relevant parameters. Central to the theory is the assumption that the observations follow a multivariate normal distribution within families. The purpose of the present investigation is to assess the effects of a certain type of departures from multivariate normality using quantitative family data on lipid and lipoprotein levels. The results show that even large departures produce reasonably unbiased parameter estimates. Whereas moderate departures lead to few inferential errors in hypothesis testing, gross departures from multivariate normality may have considerable effects on likelihood ratio tests.

Environment↗
PubMed1986

A major gene for primary hypoalphalipoproteinemia.

Sixteen kindreds were ascertained through probands clinically determined to have primary hypoalphalipoproteinemia, characterized by bottom decile high-density lipoprotein cholesterol (HDL-c), but otherwise normolipidemic. Age- and sex-adjusted, standardized HDL-c levels on 64 individuals in 14 nuclear families in which the proband was a parent were analyzed using the unified mixed model of segregation analysis as implemented in the computer program POINTER. The analysis proceeded by using the likelihood of offspring conditional on the parental phenotypes (conditional likelihood), which appears to overcome the limitation of possible heterogeneity in the selection criteria and provides an appropriate correction for the ascertainment. In these families, the multifactorial contribution to the phenotype appears to be small and significant only in the offspring generation. Although it was not possible to resolve the dominance pattern at the major locus since none of a recessive, additive, or dominant hypothesis could be firmly rejected, these families provided clear evidence for a major gene. Genetic heterogeneity is still a possibility, even within "primary" hypoalphalipoproteinemia.

Cholesterol, HDL↗
PubMed1985

A method to assess the environment for genetic studies: the Common Environment Index and the Household Relationships Interview.

Genetic and environmental influences in causing a disease are difficult to measure because of lack of precision in identification of relevant nongenetic variables. The Household Relationships Interview and Schedule was developed to measure shared common environment in families (Common Environment Index) and to take into account developmental stages throughout the life cycle and separation/disruption. Seven trained persons interviewed three individuals who reported fictitious interrelated life histories varying in length and complexity. Discrepancies between the recorded data and the true data were analyzed. Overall 96.1% of the items were recorded correctly. Thus, the method has shown good face and construct validity and reliability for measuring quantity of time shared by relatives in a common household. Common environment as measured by this instrument should be a particularly useful tool in behavior-genetic studies.

Environment↗
PubMed1985

A family study of dermatoglyphic traits in India: a search for major gene effects on palmar pattern ridge counts.

Palmar pattern ridge counts were subjected to segregation analysis in an attempt to identify possible major gene effects on these dermatoglyphic traits. The phenotypes considered were total palmar pattern ridge count, and ridge counts for the right interdigital III and IV and left interdigital IV individual palmar areas (sample sizes were too small for the other palmar areas). Evidence of familial resemblance was found for all of the phenotypes studied, and initial evidence for a major effect was found for all but the right palm interdigital III ridge count. However, this initial evidence could be attributed to nongenetic effects in each case, including skewness in the trait distribution. Tests for agreement with Mendelian transmission frequencies were found to be very useful in discriminating between a non-Mendelian major effect and a major gene. We concluded against a major gene effect for any of these traits, and multifactorial inheritance remains a plausible alternative explanation for the familial resemblance.

Dermatoglyphics↗
PubMed1985

A family study of dermatoglyphic traits in India: resolution of genetic and uterine environmental effects for palmar pattern ridge counts.

The inheritance of palmar pattern ridge counts for individual palmar areas, combined distal areas, and all ten areas combined was investigated in families belonging to two strictly endogamous Brahmin castes of peninsular India. Ridge count phenotypes were obtained by the method proposed by Malhotra et al. (1981a), however, zero observations (indicating patterns not circumscribed by triradii) were excluded from analysis. Path analytic methods were applied in order to determine the relative influences of polygenes, intrauterine environment, and residual environment. The proportion of genetic variation was, in general, consistently greater in one population than the other, and significant intrauterine environmental effects were detected for the population with lower heritabilities. The results of this investigation suggest that a simple polygenic model may not be sufficient to explain the inheritance of ridge counts in the interdigital IV configurational area. Distal pattern ridge counts do not appear to be influenced by more or less uterine environmental effects than all areas considered together. The proportion of genetic variation for the total palmar pattern ridge count was 52% in both populations.

Consanguinity↗
PubMed1985

Demonstration of a common major gene with pleiotropic effects on immunoglobulin E levels and allergy.

Atopic disease is generally recognized to be familial, although specific genetic components have yet to be identified. High levels of a unique class of immunoglobulins, immunoglobulin E (IgE), have been shown to be associated with allergies. Several investigators have reported evidence indicating a recessive regulatory locus where an individual with the homozygous recessive genotype has persistently elevated levels of IgE. Willcox and Marsh [1978] have proposed a hypothesis relating IgE production and liability to become allergic. A test of this hypothesis was carried out in the present study. Bivariate segregation analysis of IgE levels and allergy was performed on 173 nuclear families, and the results indicate that an IgE regulatory locus contributes to the familial transmission of allergy. The results are further discussed in the context of the Willcox and Marsh hypothesis.

Adult↗
PubMed1985

ABO associations with blood pressure, serum lipids and lipoproteins, and anthropometric measures.

Discriminant analysis was used to explore multivariate associations with ABO blood types in a biracial sample of 898 Bogalusa youths. Dependent variables included blood pressure (systolic and diastolic), serum lipid and lipoprotein levels (total cholesterol, alpha-, beta-, and pre-beta-lipoprotein cholesterol, and triglycerides), and anthropometric variables (height, weight, right arm length, triceps skinfold thickness, and a computed ponderal index). Analyses performed within race showed that several variables including beta-lipoprotein cholesterol, systolic blood pressure, and the ponderal index were sufficient to discriminate between individuals possessing the B antigen (B and AB) and those not possessing the B antigen (A and O) in the White subsample. However, height in itself can account for the detected difference, B individuals being taller than non-B individuals by a mean value of 2.4 cm. A concordant, but not significant effect was found in the Black subsample. Further tests support the conclusion that the strongest association is between ABO blood type and height.

ABO Blood-Group System↗