The 1080-bp coding region of the human plasma α(1,3)fucosyltransferase gene (FUT6) was sequenced in a total of 161 individuals (322 chromosomes) drawn from three populations, involving 56 Africans (Xhosa), 52 European-Africans of South Africa, and 53 Japanese. In addition to six reported base substitutions, eleven new base substitutions and a single base insertion were found in the coding region of the FUT6. Eleven functional and four null alleles were encountered, of which 10 alleles were novel alleles identified in this study. Two null alleles have been identified previously, whereas two novel null alleles, which contained a single base (cytosine) insertion at nucleotide 499, were found in a Xhosa population. The allelic distributions of FUT6 were different among these three populations. The heterozygosity of FUT6 was 0.860, 0.699, and 0.632, in Xhosa, European-African (South Africa), and in Japanese populations, respectively. The extensive DNA sequence diversity of the FUT6 may be suitable for application as a tool in genetic studies for modern human evolution.

A founder haplotype on chromosome 2p for autosomal dominant Parkinson's disease (PD) has been postulated for two families of Northern European descent, and a new mutation in the α-synuclein gene (Ala30Pro) has been found in a German PD family. We evaluated 85 German PD patients and 85 ethnically matched controls for shared markers on chromosome 2p and for the new α-synuclein mutation. We found no evidence for linkage disequilibrium, suggesting that the putative founder mutation on chromosome 2p is not a common cause of PD in the local population. Furthermore, no patient carried the Ala30Pro change, supporting earlier findings that mutations in the α-synuclein gene are extremely rare.

To dissect the genetic pathway of hypertension, we measured angiotensinogen in 685 members of 186 families recruited from a rural community in southwest Nigeria. Commingling and segregation analyses were carried out. A mixture of two and/or three distributions fits the data significantly better than a single distribution in commingling analysis, suggesting a major gene effect. Segregation analysis confirmed that a recessive major gene model for low values of angiotensinogen provides the best fit to the data and about 13% of the variance was due to the recessive gene segregation.

Apolipoprotein E (APOE = gene, apoE = protein) plays a central role in plasma lipoprotein metabolism and in lipid transport within tissues. The APOE shows a genetic polymorphism determined by three common alleles, APOE*2, APOE*3, APOE*4 and the product of the three alleles differs in several functional properties. APOE is involved in the development of certain pathological conditions. In particular, the APOE*4 allele is a risk factor for susceptibility to coronary artery disease (CAD) and Alzheimer's Disease (AD). In the present study we analyzed the APOE allele distribution in the world. The APOE*3 is the most frequent in all the human groups, especially in populations with a long-established agricultural economy like those of the Mediterranean basin (0.849–0.898). The frequency of APOE*4, the ancestral allele, remains higher in populations like Pygmies (0.407) and Khoi San (0.370), aborigines of Malaysia (0.240) and Australia (0.260), Papuans (0.368), some Native Americans (0.280), and Lapps (0.310) where an economy of foraging still exists, or food supply is (or was until the recent past) scarce and sporadically available. The APOE*2 frequency fluctuates with no apparent trend (0.145–0.02) and is absent in Native Americans. We suggest that the APOE*4, based on some functional properties it has and on its distribution among human populations, could be identified as a ‘thrifty’ allele. The exposure of APOE*4 to the contemporary environmental conditions (Western diet, longer lifespans) could have rendered it a susceptibility allele for CAD and AD. The absence of the association of APOE*4 with CAD and AD in Sub-Saharan Africans, and its presence in African Americans, seems to confirm this hypothesis.

The impact of the three most common apolipoprotein E (APOE) genotypes (ε32, ε33, and ε43) on means, variances, and correlations of nine plasma lipid and apolipoprotein traits (total cholesterol, lnTriglycerides, HDL cholesterol, and apolipoproteins AI, AII, B, CII, CIII, and lnE) was studied in 212 unrelated female and 219 unrelated male children aged 5–21.5 years from 278 pedigrees ascertained without regard to health status from Rochester, Minnesota. There was significant heterogeneity (p[les ]0.05) among genotypes for the mean plasma levels of lnApo E, Apo CII, Apo CIII, and lnTriglycerides (lnTrig) in females, and for the means of lnApo E, Apo B, and total cholesterol (Total-C) in males. Significant heterogeneity of intragenotypic variance was observed in males for Apo CII, lnTrig, and HDL-C; no significant heterogeneity was observed in females. Pairwise correlations between traits differed significantly among APOE genotypes in both females (6 of 36 pairs) and males (5 of 36 pairs). These results differ from those obtained from studies of the parental generation from the same sample of pedigrees. Our study further demonstrates that, with the exception of mean lnApo E levels, the univariate and bivariate distributions of traits that are measures of lipoprotein metabolism are influenced by variation in the APOE gene in a gender- and generation-dependent manner.

The transmission disequilibrium test (TDT), designed as a test of linkage in the presence of association (i.e. linkage disequilibrium), has received considerable attention in the recent statistical genetics literature due to its advantages over other within-family analytic methods. One limitation of the conventional TDT is its application solely to linkage disequilibrium between a genetic marker and a single categorical trait (e.g. presence or absence of a disease). In this paper, we present an extension of the TDT using logistic regression to examine the relation between a candidate gene or genetic marker and one or more continuous or categorical explanatory variables. This logistic regression extension of the TDT possesses all of the desirable features of the conventional TDT, as well as many advantages associated with traditional regression analysis. We describe the model and its properties, as well as a number of its possible applications, and apply it to examine linkage disequilibrium between the dopamine receptor D2 gene (DRD2) and symptoms of childhood attention deficit hyperactivity disorder (ADHD). We also briefly compare the logistic regression TDT to other quantitative TDTs that have been proposed in the literature, and highlight the advantages of a regression-based approach for examining the relation between a candidate gene and one or more continuous or categorical traits. Given its features, we regard the logistic regression extension of the TDT as a flexible new data analytic method with extensive potential applications to problems in medical, psychiatric, and behavioral genetics.

Twin studies are widely used to study genetic and environmental influences on human measurements. Correlations are often used in such studies to compare the levels of similarity between monozygotic and dizygotic twins with respect to a specified trait. In this paper, we compare three procedures for testing the equality of twin correlations when the outcome variable of interest is multinominal. One method is a likelihood ratio test based on an underlying Dirichlet-multinomial distribution. The second method is based on the estimated large sample variance of the estimated correlation, and the third method is based on a χ2 goodness-of-fit test. The results of a Monte Carlo simulation show that the three methods have similar properties if the number of twin pairs is large (> 100), and the prevalence of the underlying trait is not extreme. Otherwise, the goodness-of-fit approach is to be preferred. We illustrate the methods by analyzing data from a previously published smoking study.