Differences among Yanomama Indian villages: Do the patterns of allele frequencies, anthropometrics and map locations correspond?

In order to determine the degree of correspondence between sets of multivariate observations based on different kinds of traits, two new methods, derived from fundamentally different notions of “correspondence,” are adopted here and compared. Using networks or trees to represent contemporary relationships, the first method tests the similarity of the cluster or hierarchic structures implicit in two sets of data. The second approach tests the departure from perfect geometric congruence or superimposability. Computer simulation was used to generate the distributions needed for significance tests under the null hypothesis. By the first technique, we find significant correspondence among the cluster structures for geographic, allele frequency, and anthropometric data on 19 Yanomama Indian villages. The results are similar and more precise for a subset consisting of seven villages. Some of these results differ from the conclusions which would be reached with the conventional correlations based upon entries in distance tables. The direct test of congruence, used only for the data on the subset of seven villages, gives results which differ substantially from those based on cluster-structure. There are, however, similarities between the measure of congruence and the simple correlations based on entries in the distance tables. The significant correspondences observed call for some explanation. Cultural and demographic features determine the particular non-random allocation of individuals to village fragments when a village splits. These social phenomena are invoked in tentative explanation of the agreement among historical, biological, and geographic relationships of villages.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37542/1/1330390312_ftp.pd

Genetic heterogeneity and trans regulators of gene expression

Heterogeneity poses a challenge to linkage mapping. Here, we apply a latent class extension of Haseman-Elston regression to expression phenotypes with significant evidence of linkage to trans regulators in 14 large pedigrees. We test for linkage, accounting for heterogeneity, and classify individual families as "linked" and "unlinked" on the basis of their contribution to the overall evidence of linkage

Effects of cis and trans Genetic Ancestry on Gene Expression in African Americans

Variation in gene expression is a fundamental aspect of human phenotypic variation. Several recent studies have analyzed gene expression levels in populations of different continental ancestry and reported population differences at a large number of genes. However, these differences could largely be due to non-genetic (e.g., environmental) effects. Here, we analyze gene expression levels in African American cell lines, which differ from previously analyzed cell lines in that individuals from this population inherit variable proportions of two continental ancestries. We first relate gene expression levels in individual African Americans to their genome-wide proportion of European ancestry. The results provide strong evidence of a genetic contribution to expression differences between European and African populations, validating previous findings. Second, we infer local ancestry (0, 1, or 2 European chromosomes) at each location in the genome and investigate the effects of ancestry proximal to the expressed gene (cis) versus ancestry elsewhere in the genome (trans). Both effects are highly significant, and we estimate that 12±3% of all heritable variation in human gene expression is due to cis variants

FTO and MC4R Gene Variants Are Associated with Obesity in Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility in women. It is also associated with metabolic disturbances that place women at increased risk for obesity and type 2 diabetes. There is strong evidence for familial clustering of PCOS and a genetic predisposition. However, the gene(s) responsible for the PCOS phenotypes have not been elucidated. This two-phase family-based and case-control genetic study was designed to address the question of whether SNPs identified as susceptibility loci for obesity in genome-wide association studies (GWAS) are also associated with PCOS and elevated BMI. Members of 439 families having at least one offspring with PCOS were genotyped for 15 SNPs previously shown to be associated with obesity. Linkage and association with PCOS was assessed using the transmission/disequilibrium test (TDT). These SNPs were also analyzed in an independent case-control study involving 395 women with PCOS and 176 healthy women with regular menstrual cycles. Only one of these 15 SNPs (rs2815752 in NEGR1) was found to have a nominally significant association with PCOS (χ2 = 6.11, P = 0.013), but this association failed to replicate in the case-control study. While not associated with PCOS itself, five SNPs in FTO and two in MC4R were associated with BMI as assessed with a quantitative-TDT analysis, several of which replicated association with BMI in the case-control cohort. These findings demonstrate that certain SNPs associated with obesity contribute to elevated BMI in PCOS, but do not appear to play a major role in PCOS per se. These findings support the notion that PCOS phenotypes are a consequence of an oligogenic/polygenic mechanism

The Spider DMA: A miniature radial differential mobility analyzer

The Spider differential mobility analyzer (DMA) is a novel, miniaturized radial DMA developed to provide size classification in the 10–500 nm range for applications requiring high portability and time resolution. Its external dimensions are ∼12 cm in diameter by 6 cm in height (excluding tubing); it weighs ∼350 g, and is designed to operate at 0.6–1.5 L/min sheath and 0.3 L/min sample flowrates. It features a new sample inlet geometry that is designed to produce a uniform azimuthal particle distribution at the entrance of the classifier, optimized sample/sheath flow streams introduction in the classifier to minimize particle delays, and extension of the electric field interaction volume for ∼30% enhanced dynamic range. Based on three-dimensional finite element simulations of flows, electric fields, and particle trajectories, we demonstrate that the Spider DMA transfer functions can be predicted with high fidelity using a parameterized fit based on the Stolzenburg semi-analytical model. Experimental characterization of the instrument response with size-selected particles confirmed close agreement with model prediction; mobility size response is linear over three orders of magnitude in mobility span. Electrical ground shielding of the external surfaces of the DMA has been found to be necessary to avoid particle losses associated with field effects as the high voltage operating limit is approached. The mean deviation between the reference size of polystyrene latex spheres and the Spider DMA measurement is less than 2%, corroborating its high sizing precision and potential for high quality size distribution measurements

Genetic studies of the Macushi and Wapishana Indians

Blood samples from 509 Macushi (3 villages) and 623 Wapishana (11 villages) of Northern Brasil and Southern Guyana have been analyzed with respect to the phenotype and gene frequencies at the following 12 polymorphic loci: AB0, Kell-Cellano, MNSs, Rh, P, Duffy, Kidd, Diego, Lewis, Group-specific component, and the immunoglobulin allotypes of the Gm and Inv systems. The data suggest that 5–6% of the Wapishana gene pool is derived from non-Indians but only 1–2% of the Macushi. Inter- and intratribal genetic distances between villages are calculated for these data in an effort to understand gene flow between the tribes and to account for the unusual distribution of a newly-discovered genetic polymorphism of erythrocyte esterase A thus far limited to these 2 tribes (Neel et al., 1977). The data are puzzling and consistent with the possibility that both the Craib-speaking Macushi and the Arawak-speaking Wapishana have derived the esterase A allele in question from some third group now extinct or thus far undiscovered. Intertribal genetic distances based on gene frequencies at 6 loci are derived for 20 Amerindian tribes (including these 2); the “central” position of these 2 tribes can in part be explained by the active migration matrix connecting them.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47606/1/439_2004_Article_BF00393584.pd

Genetic studies of the Macushi and Wapishana Indians

Blood samples from 509 Macushi and 623 Wapishana Amerindians of Northern Brazil and Southern Guyana have been analyzed with reference to the occurrence of rare variants and genetic polymorphisms of the following 25 systems: (i) Erythrocyte enzymes : acid phosphatase-1, adenosine deaminase, adenylate kinase-k, carbonic anhydrase-1, carbonic anhydrase-2, esterase A 1,2,3, esterase D, galactose-1-phosphate uridyltransferase, isocitrate dehydrogenase, lactate dehydrogenase, malate dehydrogenase, nucleoside phosphorylase, peptidase A, peptidase B, phosphoglucomutase 1, phosphoglucomutase 2, phosphogluconate dehydrogenase, phosphohexoseisomerase, triosephosphate isomerase and (ii) Serum proteins : albumin, ceruloplasmin, haptoglobin, hemoglobin A, hemoglobin A 2 and transferrin. Fifteen different rare variants were detected, involving 11 of these systems. In addition, a previously undescribed variant of ESA 1,2,3 which achieves polymorphic proportions in both these tribes is described. Excluding this variant, the frequency of rare variants is 1.1/1000 in 12510 determinations in the Macushi and 4.7/1000 in 15 396 determinations in the Wapishana. The ESA 1,2,3 , polymorphism was not observed in 382 Makiritare, 232 Yanomama, 146 Piaroa, 404 Cayapo, 190 Kraho and 112 Moro. Irregularities in the intratribal distribution of this polymorphism in the Macushi and Wapishana render a decision as to the tribe of origin impossible at present. Gene frequencies are also given for previosly described polymorphisms of 5 systems: haptoglobin, phosphoglucomutase 1, erythrocyte acid phosphatase, esterase D, and galactose-1-phosphate-uridyl-transferase.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47605/1/439_2004_Article_BF00390440.pd