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B K Suarez

Publications and source records attributed to B K Suarez.

71 records · Page 4Linked to original sources
PubMed1982

Ascertainment bias for non-twin relatives in twin proband studies.

When families are ascertained through affected twins, as for example when twin probands are selected from a registry and their non-twin relatives studied, a correction for ascertainment bias is needed. It is shown that probandwise counting (where relatives of doubly ascertained twin pairs are counted twice) is the appropriate method. The bias resulting from pairwise counting is given and depends on the genetic model and on the probability of selecting an affected twin as a proband. For the multifactorial and generalized single major locus models the bias is small, and the problems associated with nonindependent ascertainment are negligible in practice.

Chromosome Mapping↗
PubMed1982

Refutation of the general single-locus model for the etiology of schizophrenia.

All published studies on the familial incidence of schizophrenia appropriate for testing the applicability of the general single-locus two-allele model are examined under the assumption of a unitary etiology for all schizophrenia. We show that the single major locus model is inadequate to predict the incidence in four classes of relatives of schizophrenic probands (parents, siblings, monozygotic, and dizygotic cotwins). In addition, the observed proportion of affected offspring from dual matings differ significantly from the model's prediction. The lack of an overall fit between the published familial distributions and the monogenic model suggests that a single major locus is insufficient for the etiology of schizophrenia. Further efforts in examining multifactorial models, mixed models, and other transmission models may be fruitful.

Chromosome Mapping↗
PubMed1981

Type I (insulin dependent) diabetes mellitus. Is there strong evidence for a non-HLA linked gene?

A recent investigation of families containing two and three consecutive generations affected with Type I (insulin dependent) diabetes mellitus has led to speculation that there is a second susceptibility gene, not linked to the major histocompatibility complex. These families differ in important respects from families which have provided the strongest evidence for HLA linkage, namely, families with two or more affected siblings. Computer simulations were designed to test the hypothesis that these two types of families were drawn from the same population of insulin dependent patients. The results indicate that this hypothesis is tenable and that the consecutive generation families probably failed to yield strong evidence for an HLA linked susceptibility gene because of ascertainment bias combined with probable incorrect specifications of the mode of inheritance of insulin dependent diabetes.

Computers↗
PubMed1981

Characterization of apolipoprotein E (ApoE) apoprotein levels in the various ApoE phenotypes.

Upon isoelectric focusing, the apolipoprotein E (apoE) system in man demonstrates at least five subspecies. The system constitutes a complex polymorphism that gives rise to five genetically determined phenotypes. Patients with type III hyperlipoproteinemia are markedly deficient in the apoE-3 subspecies. In order to determine whether the various phenotypes differ with respect to the total amount of protein present, we measured the apoE levels in plasma by RIA in six families ascertained through a well documented type III proband. ApoE-3-deficient homozygotes were found to have significantly more protein than heterozygotes who, in turn, had significantly more protein than normal homozygotes. These differences remained significant after allowance was made for the correlated effects of very low density lipoproteins cholesterol and very low density lipoproteins triglycerides. Among heterozygotes, persons with the fifth isoelectric focusing band (apoE-4) were found to have significantly less apoE protein than heterozygotes without this band. A similar but nonsignificant trend was observed in normal homozygotes. These observations are consistent with the hypothesis that the primary defect in type III hyperlipoproteinemia subspecies to another.

Apolipoproteins↗
PubMed1980

Sibling sex ratio and male homosexuality.

As an explanation for the increased sex ratio observed in the sibships of male homosexuals, Slater has hypothesized that the increase, itself, may be a causative factor in predisposing a male to homosexual behavior. As a test of this hypothesis, an additive and a multiplicative risk model relating male homosexuality to the sexual configuration of the homosexual's sibship were formulated and tested against published data. Both models were found to predict a curvilinear decrease in sibling sex ratio as sibship size increased, and both models were found to fit the observed sibship size sex ratio data closely. The analysis suggests that approximately 10% of the variance in male homosexual behavior can be accounted for by the sexual configuration of the homosexual's sibship.

Family Characteristics↗
PubMed1979

A simple method to detect linkage for rare recessive diseases: an application to juvenile diabetes.

A simple procedure designed specifically to detect linkage for rare recessive diseases is described. The method uses information on identity by descent scores for a pair of sibs at a marker locus conditioned on the number of affected sibs in the pair. A procedure for estimating the recombination fraction is described, and a table facilitating the likelihood ratio test of linkage is provided. The method, when applied to a collection of multiplex families segregating for juvenile diabetes mellitus, suggests the possibility that this disease is linked to the HLA complex. The method is found to compare favorably to the maximum likelihood approach, for which the computer program LIPED gives a maximum lod score of 2.48 at a male and female recombination fraction of theta = 0.20.

Diabetes Mellitus, Type 1↗
PubMed1979

Variability in sib pair genetic identity.

Using a realistic model of meiotic crossing over the variability in full sib genetic identity is estimated by simulating 200 independent pairs of sibs. The standard deviation of the percentage of the autosomal genome identical by descent (IBD) was found to be about 0.056. Simulations of sibships larger than size two revealed that the average within sibship standard deviation is between 0.054 and 0.056, thus indicating that sib pair variability is insensitive to the nonindependence structure present when considering all possible sib pairs contained in a large sibship.

Chromosomes, Human↗
PubMed1979

A three-dimensional model of dentin apposition.

Since we have found that conventional methods of dentin apposition measurements are inaccurate, we have devised a three dimensional model. This model allows the investigator to measure dentin apposition volumetrically, and simultaneously consider odontoblast activity and the geometric relationships which influence the configuration of the dentin.

Animals↗
PubMed1978

The affected sib pair IBD distribution for HLA-linked disease susceptibility genes.

The distribution of identity by descent (IBD) scores for sib pairs affected with a disease determined by a disease susceptibility (DS) locus tightly linked to the HLA complex is derived. It is shown that the sib pair IBD distribution differs from its a priori distribution and, moreover, is completely specified by three observable population parameters--the additive and dominance variances and the prevalence of the disease in the population. An application of the model is illustrated using data on juvenile diabetes mellitus.

Chromosome Mapping↗
PubMed1978

The generalized sib pair IBD distribution: its use in the detection of linkage.

General expression for the distribution of identity by descent (IBD) scores at a marker locus have been derived given neither, one or both sibs affected with a disorder determined by a linked trait locus with arbitrary gene frequency and penetrance vector. It is shown that the distirbution of IBD scores depends only on the additive and dominance variances and the population prevalence of the disorder. A one-sided test is suggested as an appropriate means of statistically testing the hypothesis that the recombination fraction is significantly less than 1/2. This sib pair approach is designed primarily to detect the presence of a critical disease susceptibility locus but when the assumptions of the incompletely penetrant single locus model are correct the methodology proposed here results in consistent estimates of the recombination fraction. The affected sib pair methodology seems especially suited to traits determined by single loci with non-Mendelian transmission.

Alleles↗
PubMed1977

Estimating the parameters of the incompletely penetrant single locus model using multiple populations.

A method involving the comparison of two or more populations is suggested as a means of obtaining a unique solution to the parameters of the incompletely penetrant single locus model. The proposed method allows a test of the assumptions of the model when three or more populations are compared. Equations that allow the inclusion of data on twin concordance rates and/or the proportion of affected children given neither, one or both parents affected are also given. Finally, some implications of fitting the model are discussed in terms of genetic counseling, residual environmental variance and the concept of heritability as applied to dichotomous traits.

Female↗
PubMed1976

Limits of the general two-allele single locus model with incomplete penetrance.

A graphical method is presented that allows an investigator to find the mathematical limits of the general one locus two allele genetic model for any trait whose population prevalence is known. It is seen that while the model is quite flexible in its ability to fit family data, there remains a large area where the model cannot be fitted. Specific sub-regions corresponding to particular hypotheses (e.g. underdominant v. intermediate v. overdominant) can be found, thereby limiting the area that needs to be searched by other more complicated techniques. Moreover, knowledge of where a set of observations lies can enable an investigator to frame and test specific subhypotheses.

Alleles↗
PubMedDate not supplied

Patterns and correlates of genetic variation in South Amerindians.

Gene frequency data from six polymorphic blood group systems in 70 South American Indian populations are used to derive synthetic gene frequency maps that document the geographical pattern of genetic variation. Additional analyses are directed toward the elucidation of mechanisms that give rise to or maintain the observed distributions. Variables of local ecology do not appear to explain gene frequency distributions in South America. Instead, local isolation and the action of stochastic forces appears to be the most parsimonious explanation of the observed geographical patterns. This is distinctly different from the geographical patterns of genetic variation seen in other continents.

Alleles↗
PubMedDate not supplied

Dopamine D2 receptor RFLPs, haplotypes and their association with substance use in black and Caucasian research volunteers.

Alleles of the dopamine D2 receptor gene are distinguished by polymorphic A and B TaqI sites approximately 10 kb 3' to the final exon and bordering the second exon, respectively. These alleles have been reported to be more prevalent in heavy substance users than in control populations in several, although not all studies. Meta-analyses of combined data from available work support significant association. Two competing hypotheses could explain this association: (1) the A1 and B1 RFLPs are in linkage disequilibrium with a functional allelic determinant that in some way influences behavior; (2) the affected subjects are drawn disproportionately from populations stratified on the basis of, for example, ethnicity that happen to have higher A1 and B1 RFLP frequencies. We report here data collected from 616 substance-abusing and control individuals that document substantial differences in A1 RFLP frequencies between white and black Americans, the almost exclusive presence of the A3 RFLP in blacks, and low frequencies of rare A4 and B3 RFLPs. In blacks, neither the A1 nor B1 RFLPs display association with substance use, while white individuals display significant association with polysubstance use. When expressed as a percent of the maximum possible disequilibrium, both white and black individuals display strong linkage disequilibrium between these loci, although blacks display many more A1/B2 chromosomes. These racial differences in TaqI RFLP haplotypes underscore the need for caution in interpreting allelic associations when careful matching for ethnicity has not been performed.

Alleles↗