Immunoglobulin Allotypes in Several North American Eskimo Populations

This is the published version. Copyright 1990 Wayne State University Press.Genetic data consisting of immunoglobulin testing (GM and KM) from 631 Eskimos from 5 populations are reported. These populations are Savoonga, Gambell (St. Lawrence Island), Wales, King Island, and Mckenzie Delta, Baffin Island. The GM and KM haplotypes are analyzed and compared to those occurring in Greenland, Canadian, Alaskan, and Siberian Eskimos and to other Siberian indigenous populations. These analyses suggest that during the peopling of the New World, four separate migrant groups crossed Beringia at various times

Immunoglobulin Haplotypes: Markers of Reproductive Success?

This is the published version. Copyright 1990 Wayne State University Press.Immunoglobulin haplotypes are highly polymorphic and are useful for analyses of both macro-and microdifferentiation of populations. The origins of this diversity are not known, but recent reports suggest strong selection at this locus. Increased rates of first-trimester spontaneous abortions have been reported when parents share GM phenotypes. Reduced fertility has been observed in mixed European descent white and Hutterite populations when both parents share immunoglobulin haplotypes. Population samples with completed family information and GM haplotype data are rare; the objective here is to provide this information on another sample. A sample of 242 Mennonite couples with mothers older than 40 years was divided into 3 groups of matings based on how many haplotypes were shared: 0, 1, or 2. The distribution of mean completed family sizes for the three groups were 3.35 ± 1.85 (n = 23), 3.47 ± 1.69 (n = 128), and 3.37 ± 1.60 (n = 91), respectively; these values were not significantly different (F = 0.145, p = 0.865). The log-rank test was used to compare the time-to-next-birth curves. The intervals between first and later births (2-4 births) were not significantly different for the three subgroups either. There is also only limited evidence for segregation distortion in another sample of 923 offspring (in which at least one parent is heterozygous)

Patterns of DNA Methlyation across the Leptin Core Promoter in Four Diverse Asian and North American Populations

DNA methylation is the most widely studied of epigenetic mechanisms, with environmental effects recorded through patterned attachments of methyl groups along the DNA that are capable of modifying gene expression without altering the DNA sequencing. The degree to which these patterns of DNA methylation are heritable, the expected range of normality across populations, and the phenotypic relevance of pattern variation remain unclear. Genes regulating metabolic pathways appear to be vulnerable to ongoing nutritional programming over the life course, as dietary nutrients are significant environmental determinants of DNA methylation, supplying both the methyl groups and energy to generate the methylation process. Here we examine methylation patterns along a region of the metabolic gene leptin (LEP). LEP's putative functions include regulation of energy homeostasis, with its signals affecting energy intake and expenditure, adipogenesis and energy storage, lipid and glucose metabolism, bone metabolism, and reproductive endocrine function. A pattern of differential methylation across CpG sites of the LEP core promoter has been previously identified; however, any consistency of pattern or its phenotypic significance is not fully elucidated among populations. Using DNA extracted from unfractionated white blood cells of peripheral blood samples, our pilot study, divided into two parts, examined the significance of variation in DNA methylation patterns along the leptin core promoter in four populations (phase 1) and used biomarkers reflecting leptin's functional process in two of those populations, western Buryat of Siberia and the Mennonite of central Kansas, to investigate the relevance of the ethnic variation identified in the DNA methylation (phase 2). LEP's core promoter region contains both the binding site for C/EBPα (CCAAT/enhancer binding protein alpha), which tempers the final step in adipocyte maturity and capacity to synthesize leptin, and the TATA motif controlling leptin synthesis. Previous studies report that increased methylation in this region is correlated to decreased gene expression, suggesting tissue-specific methylation variation at this region (Melzner et al. 2002). We hypothesized that evidence of nutritional epigenetic programming would be identified through variation in patterns of DNA methylation and that functional relevance of that variation among populations would be identified through biomarkers that reflect leptin's metabolic signals: serum leptin levels, lipoproteins of the lipid transport system, and anthropometric measures. In phase 1, our combined analyses of 313 individuals documented a distinct and consistent overall pattern of differential DNA methylation across seven CpG sites of LEP core promoter in all ethnicities and both sexes. This pattern replicates those identified in previous studies, suggesting a conserved core promoter region across populations. Phase 2 analyses of two of the four populations (n = 239), correlating methylation at the C/EBPα transcription binding site (TBS) with metabolic and anthropometric biomarkers reflecting LEP roles, showed that stature, which reflects bone growth and remodeling, was significantly and inversely correlated with the percentage of DNA methylation at this site in both sexes. We suggest that variation in DNA methylation along the LEP core promoter plays a substantial role in energy signals affecting both adipogenesis and bone metabolism

Immunoglobulin haplotype frequencies in Anabaptist population samples: Kansas and Nebraska Mennonites and Indiana Amish

This is the published version, also available here: http://www.jstor.org/stable/41465452

The Black Caribs (Garifuna) of Livingston, Guatemala: Genetic Markers and Admixture Estimates

This is the published version. Copyright 1981 Wayne State University Press.The Black Caribs (Garifuna) are descendants of West African and Amerindian groups from St. Vincent Island who were transplanted to the coast of Central America in 1797. The founding population, estimated at 2,500 to 5,000 persons, gave rise to 65,000 Black Caribs who presently reside in 54 fishing villages spread geographically from Stann Creek (Dangriga), Belize, to LaFe, Nicaragua. This paper documents the genetic variation observed for 24 blood group, red blood cell and serum protein systems in one of the Black Carib communities of Livingston, Guatemala. Admixture estimates, based upon Gm, suggest the following parental population contribution for Livingston: 70% African, 29% Indian and 1% European

VNTR DNA Variation in Siberian Indigenous Populations

This is the published version. Copyright 1995 Wayne State University Press.The VNTR loci D7S104, D11S129, D18S17, D20S15, and D21S112 in three indigenous Siberian populations were analyzed to determine the populations' genetic structure. Using the Kolmogorov- Smirnov test, we found that the Siberian indigenous populations of Surinda and Sulamai are separated at the D1 IS 129 locus (p < 0.05). However, the population of Poligus is genetically homogeneous compared with the villages of Sulamai and Surinda. Principal component plots for the sets of VNTR loci cluster the Siberian groups together, reflecting the homogeneity of these populations. An analysis of mean per locus heterozygosity versus the distance from the centroid of distribution suggests gene flow into Sulamai but little genetic exchange with Surinda and Poligus. Ultimately, the VNTR data reflect the genetic distinctiveness of the Kets and the Evenki

Immunoglobulin GM 3 23 5,13,14 phenotype is strongly associated with IgG1 antibody responses to Plasmodium vivax vaccine candidate antigens PvMSP1-19 and PvAMA-1

<p>Abstract</p> <p>Background</p> <p>Humoral immune responses play a key role in the development of immunity to malaria, but the host genetic factors that contribute to the naturally occurring immune responses to malarial antigens are not completely understood. The aim of the present investigation was to determine whether, in subjects exposed to malaria, GM and KM allotypes--genetic markers of immunoglobulin γ and κ-type light chains, respectively--contribute to the magnitude of natural antibody responses to target antigens that are leading vaccine candidates for protection against <it>Plasmodium vivax</it>.</p> <p>Methods</p> <p>Sera from 210 adults, who had been exposed to malaria transmission in the Brazilian Amazon endemic area, were allotyped for several GM and KM determinants by a standard hemagglutination-inhibition method. IgG subclass antibodies to <it>P. vivax </it>apical membrane antigen 1 (PvAMA-1) and merozoite surface protein 1 (PvMSP1-19) were determined by an enzyme-linked immunosorbent assay. Multiple linear regression models and the non-parametric Mann-Whitney test were used for data analyses.</p> <p>Results</p> <p>IgG1 antibody levels to both PvMSP1-19 and PvAMA-1 antigens were significantly higher (<it>P </it>= 0.004, <it>P </it>= 0.002, respectively) in subjects with the GM 3 23 5,13,14 phenotype than in those who lacked this phenotype.</p> <p>Conclusions</p> <p>Results presented here show that immunoglobulin GM allotypes contribute to the natural antibody responses to <it>P. vivax </it>malaria antigens. These findings have important implications for the effectiveness of vaccines containing PvAMA-1 or PvMSP1-19 antigens. They also shed light on the possible role of malaria as one of the evolutionary selective forces that may have contributed to the maintenance of the extensive polymorphism at the GM loci.</p

Immunoglobulin Allotypes in European Populations: III. Gm, Am and Km Allotypes in People of European Ancestry in the United States

Political boundaries and locations of European peoples have been drastically altered by two world wars. Obtaining sufficient genetic information for interpreting European gene frequencies in terms of ethno-historical and linguistic data becomes a difficult task when data have not been available for certain countries. Some of these problems can be circumvented if immigrants to the U.S. or their descendants are used as representatives of pre-World War I Europeans. Sera from 1,975 European immigrants and their descendants were collected from donors whose response to questionnaires indicated that their four grandparents originated from the same geopolitical unit. The sera were tested for Glm(f, z, a, and x), G3m(b0, 1, 3, 5, c3,5, g, s, and t), A2m (1 and 2) and Km(l). The haplotype frequencies observed for immigrants to the United States were not significantly different from data published on indigenous Europeans. This is the first report of uncommon Gm haplotypes in many of the populations studied. The present study analyzes the distribution of infrequent haplotypes in central and eastern Europe. Some of these haplotypes are found in high frequency in Asiatic populations (Gmf,a:b, Gmz,a:b\u27s,t and Gmz,a:b), suggesting that their presence is due to Asian admixture rather than recombination or mutation. Asian admixture was estimated to be highest in eastern and central Europe and lowest in northern and western Europe. Finally, the results document a genetic basis for the long standing practice of using U.S. populations to represent indigenous European populations for genetic studies when the European populations are not available for study

Surname Analysis as a Sampling Method for Recovery of Genetic Information

An effective means of retrieving ethnic information on a population sample for which there is already medical information may be surname analysis, but this has never been tested. Thus, two methods of surname classification were used to select individuals with German, Italian, Irish and Polish surnames from a sample of 2306 Milwaukee immigrants and offspring of immigrants. This sample represented only those individuals who identified all grandparents as coming from the same European geopolitical unit, and all had been previously tested for Glm(f, z, a and x), G3m(b0, bl, b3, b4 and g), A2m(l and 2), and Km(l). Selected sera were tested for G3in(s, t, c3 and c5). The Gm haplotype frequencies of the surname groups were then compared (by z-scores) with those of the German, Italian, Irish, and Polish groups as defined by grandparental origin. There are no statistically significant differences in haplotype frequency between the ethnic categories as determined by grandparents and those determined by surname even when both sexes are considered. Medical records in this country are not likely to include such a high percentage of “pures” but the researcher attempting to use medical records would be wise to select a sample considering both surname and home address in cities with localized ethnic communities