Sample-size calculations in segregation analysis

Segregation analysis, employing nuclear families, is the most frequently used method to evaluate the mode of inheritance of a trait. To our knowledge, there exists no tabular information regarding the sample sizes required of individuals and families needed to perform a significance test of a specific segregation ratio for a predetermined power and significance level. To fill this gap, we have developed sample-size tables based on the asymptotic variance of the maximum likelihood estimate of the segregation ratio and on the normal approximation for two-sided hypothesis testing. Assuming homogeneous sibship size, minimum sample sizes were determined for testing the null hypothesis for the segregation ratio of 1/4 or 1/2 vs. alternative values of .05-.80, for the significance level of .05 and power of .8, for ascertainment probabilities of nearly 0 to 1.0, and sibship sizes 2-7. The results of these calculations indicate a complex interaction of the null and the alternate hypotheses, ascertainment probability, and sibship size in determining the sample size required for simple segregation analysis. The accompanying tables should aid in the appropriate design and cost assessment of future genetic epidemiologic studies.     

Respiration,ATP level,and sugar accumulation in potato tubers during storage at 4°

A kinetic study was made of the relationship between respiration rate, sugar content and ATP levels, in fresh and aged potato tubers stored at 4°. The ATP content in tubers rose rapidly immediately after the chilling stress, while respiration rate decreased below the initial rate and sugar accumulation was not detected. After 4 days of storage, the ATP level declined and the sugars started to accumulate. The typical increase in respiration rate that usually follows chilling stress, appeared only in fresh tubers (at about the 6th day of storage). In dinitrophenol-treated tubers, the ATP level remained below the initial level and sugar accumulation was blocked completely. The evidence presented suggests that ATP elevation is not generated by the respiration burst.     

Catechol oxidase from green olives: Properties and partial purification

Catechol oxidase was extracted from an acetone powder prepared from green olive. The enzyme was purified 240-fold by ammonium sulphate fractionation followed by ion exchange chromatography and gel filtration. The enzyme was characterized by substrate specificity and response to inhibitors. Between 7 and 9 bands having catechol oxidase activity could be detected by gel electrophoresis and electrofocusing. The purified enzyme had an estimated MW of 42 000. The enzyme was strongly inhibited by diethyldithiocarbamate. Inhibition by chloride was strongly dependent on pH. The enzyme did not oxidise monophenols.     

High-resolution linkage mapping for susceptibility genes in human polygenic disease: Insulin-dependent diabetes mellitus and chromosome 11q

Insulin-dependent diabetes mellitus (IDDM) has a complex pattern of genetic inheritance. In addition to genes mapping to the major histocompatibility complex (MHC), several lines of evidence point to the existence of other genetic susceptibility factors. Recent studies of the nonobese diabetic mouse (NOD) model of IDDM have suggested the presence, on mouse chromosome 9, of a susceptibility gene linked to the locus encoding the T-cell antigen, Thy-1. A region on human chromosome 11q is syntenic to this region on mouse chromosome 9. We have used a set of polymorphic DNA markers from chromosome 11q to investigate this region for linkage to a susceptibility gene in 81 multiplex diabetic pedigrees. The data were investigated by maximization of lod scores over genetic models and by multiple-locus affected-sib-pair analysis. We were able to exclude the presence of a susceptibility gene (location scores less than -2) throughout greater than 90% of the chromosome 11q homology region, under the assumption that the susceptibility factor would cause greater than 50% of affected sib pairs to share two alleles identical by descent. Theoretical estimates of the power to map susceptibility genes with a high-resolution map of linked markers in a candidate region were made, using HLA as a model locus. This result illustrates the feasibility that IDDM linkage studies using mapped sets of polymorphic DNA markers have, both for other areas of the genome in IDDM and for other polygenic diseases. The analytic approaches introduced here will be useful for affected-sib-pair studies of other complex phenotypes.     

Abelson murine leukemia virus-induced tumors elicit antibodies against a host cell protein, P50.

When BALB/c mice were injected with a syngeneic cell line transformed by Abelson murine leukemia virus (A-MuLV), the tumor was usually lethal. In sera from tumor-bearing mice, and at highest levels in sera from mice that reject their tumors, was an antibody that immunoprecipitates a specific protein from [35S]-methionine-labeled A-MuLV-transformed BALB/c cells. This protein was not the previously characterized A-MuLV-specific protein (P120) but a 50,000-molecular-weight protein (P50). Such sera may also immunoprecipitate P120, but no other protein was reproducibly precipitated by them. A monoclonal antibody (RA3-2C2) that has been shown to stain normal B-lymphocytes also selectively immunoprecipitated P50. P50 was present in A-MuLV-transformed lymphoid and fibroblastic cells of a variety of mouse strains. One A-MuLV-transformed cell line had a very low P50 level, the L1-2 tumor of C57L origin. This tumor was previously shown to be rejected by C57L mice and is used to produce anti-P120 (anti-AbT) sera. P50 was not a Moloney MuLV protein and was found at low levels in normal cells of cells transformed by agents other than A-MuLV; thus, it was probably a host cell protein whose concentration was selectively accentuated by A-MuLV transformation. P50 was phosphorylated and, by using indirect immunofluorescence, anti-P50 serum stained live A-MuLV-transformed cells. The protein was not glycosylated and did not label by lactoperoxidase-catalyzed iodination. Thus, P50 was very like P120 in its cellular localization and properties, but it did not exhibit proptein kinase activity in vitro. The selective accentuation of this protein in A-MuLV transformants and its strong antigenicity in syngeneic animals suggest that it is a unique and functionally important protein.     

Elimination of suppressor T-cells in mice undergoing a graft-versus-host reaction expressed by increased response to polyvinylpyrrolidone (PVP).

Mice undergoing a mild GVHR exhibited an enhanced response to PVP considered to be independent of T-helper function and simultaneously, a decreased response to SRBC, known to be T-cell dependent. Such mice had a reduced number of T cells in their spleens expressed by a lower reactivity to T-lectins PHA and Con A and by a decrease in the number of cells killed by anti θ serum. These mice did not show, however, a substantial change in the activity of B lymphocytes contained in their spleens, since the PFC and the mitogenic response to LPS, as well as the number of immunoglobulin bearing cells were similar to that of controls. These results suggest that the enhanced response to PVP in mice undergoing a mild GVHR is a result of the elimination of a certain T-cell population which seems to regulate the immune response to this antigen.     

Body Adiposity Index versus Body Mass Index and Other Anthropometric Traits as Correlates of Cardiometabolic Risk Factors

Objective

The worldwide prevalence of obesity mandates a widely accessible tool to categorize adiposity that can best predict associated health risks. The body adiposity index (BAI) was designed as a single equation to predict body adiposity in pooled analysis of both genders. We compared body adiposity index (BAI), body mass index (BMI), and other anthropometric measures, including percent body fat (PBF), in their correlations with cardiometabolic risk factors. We also compared BAI with BMI to determine which index is a better predictor of PBF.

Methods

The cohort consisted of 698 Mexican Americans. We calculated correlations of BAI, BMI, and other anthropometric measurements (PBF measured by dual energy X-ray absorptiometry, waist and hip circumference, height, weight) with glucose homeostasis indices (including insulin sensitivity and insulin clearance from euglycemic clamp), lipid parameters, cardiovascular traits (including carotid intima-media thickness), and biomarkers (C-reactive protein, plasminogen activator inhibitor-1 and adiponectin). Correlations between each anthropometric measure and cardiometabolic trait were compared in both sex-pooled and sex-stratified groups.

Results

BMI was associated with all but two measured traits (carotid intima-media thickness and fasting glucose in men), while BAI lacked association with several variables. BAI did not outperform BMI in its associations with any cardiometabolic trait. BAI was correlated more strongly than BMI with PBF in sex-pooled analyses (r = 0.78 versus r = 0.51), but not in sex-stratified analyses (men, r = 0.63 versus r = 0.79; women, r = 0.69 versus r = 0.77). Additionally, PBF showed fewer correlations with cardiometabolic risk factors than BMI. Weight was more strongly correlated than hip with many of the cardiometabolic risk factors examined.

Conclusions

BAI is inferior to the widely used BMI as a correlate of the cardiometabolic risk factors studied. Additionally, BMI’s relationship with total adiposity may not be the sole determinate of its association with cardiometabolic risk.