Immunoglobulin Haplotypes – Markers of Reproductive Success

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)

Genetic Admixture and Gallbladder Disease in Mexican Americans

Gallbladder disease is a common source of morbidity in the Mexican American population. Genetic heritage has been proposed as a possible contributor, but evidence for this is limited. Because gallbladder disease has been associated with Native American heritage, genetic admixture may serve as a useful proxy for genetic susceptibility to the disease in epidemiologic studies. The objective of our study was to examine thepossibility that gallbladder disease is associated with greater Native American admixture in Mexican Americans. This study used data from the Hispanic Health and Nutrition Examination Survey and was based on 1,145 Mexican Americans who underwent gallbladder ultrasonography and provided usable phenotypic information. We used the GM and KM immunoglobulin antigen system to generate estimates of admixture proportions and compared these for individuals with and without gallbladder disease. Overall, the proportionate genetic contributions from European, Native American, and African ancestries in our sample were 0.575, 0.390, and 0.035, respectively. Admixture proportions did not differ between cases and noncases: Estimates of Native American admixture for the two groups were 0.359 and 0.396, respectively, but confidence intervals for estimates overlapped. This study found no evidence for the hypothesis that greater Native American admixture proportion is associated with higher prevalence of gallbladder disease in Mexican Americans. Reasons for the finding that Native American admixture proportions did not differ between cases and noncases are discussed. Improving our understanding of the measurement, use, and limitations of genetic admixture may increase its usefulness as an epidemiologic tool as well as its potential for contributing to our understanding of disease distributions across populations

Immunoglobulin Haplotype Frequencies in Anabaptist Population Samples: Kansas and Nebraska Mennonites and Indiana Amish

Anabaptist history is a chronicle of repeated migrations, fissions, and fusions of various subgroups. The effects of these events should be evident in the population biology of the Anabaptist groups. No prior genetic studies have included the polymorphic and highly informative immunoglobulin markers. Here, 685 serum samples representing 1 Amish and 3 Mennonite community samples (7 congregations) were studied for immunoglobulin allotypes. The haplotypes IGHG*F B, IGHG*A,Z G, and IGHG*A,X,Z G range in frequency from 0.542 to 0.765, 0.123 to 0.290, and 0.075 to 0.170, respectively. IGK*1 frequencies range from 0.035 to 0.077, All frequencies are within expected ranges for central and western European population samples, There was considerable intergroup variability among the Anabaptist samples that was statistically significant x29 = 22.63, 0.005 \u3c p \u3c 0.01), Principal component analyses, including the immunoglobulin allotype frequencies and published data on ABO, MN, and Rhesus (Dd) markers, demonstrate that the Mennonite congregation samples with close historical ties group together acid are distinct from the Amish and Meridian congregation samples

Mitochondrial Genetic Diversity and its Determinants in Island Melanesia

For a long time, many physical anthropologists and human geneticists considered Island Melanesian populations to be genetically impoverished, dominated by the effects of random genetic drift because of their small sizes, internally very homogeneous, and therefore of little relevance in reconstructing past human migrations. This view is changing. Here we present the developing detailed picture of mitochondrial DNA (mtDNA) variation in eastern New Guinea and Island Melanesia that reflects linguistic distinctions within the region as well as considerable island-by-island isolation. It also appears that the patterns of variation reflect marital migration distinctions between bush and beach populations. We have identified a number of regionally specific mtDNA variants. We also question the widely accepted hypothesis that the mtDNA variant referred to as the ‘Polynesian Motif’ (or alternatively the ‘Austronesian Motif’) developed outside this region somewhere to the west. It may well have first appeared among certain non-Austronesian speaking groups in eastern New Guinea or the Bismarcks. Overall, the developing mtDNA pattern appears to be more easily reconciled with that of other genetic and biometric variables

Immunoglobulin Allotypes (GM and KM) Indicate Multiple Founding Populations of Native Americans: Evidence of at Least Four Migrations to the New World

On the basis of GM and KM typing and language, approximately 28,000 Amerindians were divided into 4 groups of populations: non-Nadene South American (8 groups), non-Nadene North American (7 groups), Nadene (4 groups), and Eskaleuts (6 groups). These groups were compared to four groups of Asian populations. The distribution of GM haplotypes differed significantly among and within these groups as measured by chi-square analysis. Furthermore, as reflected in a maximum linkage cluster analysis, Amerindian populations in general cluster along geographic divisions, with Eskaleuts and Nadenes clustering with the Asian populations and non-Nadene North American and non-Nadene South American populations forming two additional clusters. Based on GM haplotype data and other genetic polymorphisms, the divisions appear to reflect populations that entered the New World at different times. It appears that the South American non-Nadene populations are the oldest, characterized by the haplotypes GM*A G and GM*X G, whereas later North American non-Nadene populations are characterized by high frequencies of GM*A G and low frequencies of GA/*X G and GM*A T. In contrast, Eskaleuts appear to have only GM*A G and GM*A T. The Nadene speakers have GM*X G and GM*A T in higher and approximately equal frequencies. Maximum linkage cluster analysis places the Alaskan Athapaskans closest to northwestern Siberian populations and the Eskaleuts closest to the Chukchi, their closest Asian neighbor. These analyses, when combined with other data, suggest that, in the peopling of the New World, at least four separate migrant groups crossed Beringia at various times. It appears likely that the South American non-Nadene entered the New World before 17,000 years b . p . and that the North American non-Nadene entered in the immediate postglacial period, with the Eskaleut and Nadene arriving at a later date

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 G3m(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

Gluten-sensitive Enteropathy IMMUNOGLOBULIN G HEAVY-CHAIN (Gm) ALLOTYPES AND THE IMMUNE RESPONSE TO WHEAT GLIADIN

radioimmunoassay in 30 Caucasians with gluten-sensitive enteropathy (GSE). 22 GSE patients maintained on a gluten-free diet for 1.5 to 20 yr (mean duration 76 mo) had elevated serum concentrations of IgG antigliadin antibody. Among GSE patients on a glutenfree diet, antigliadin antibody was seen only in those having the chromosome 14-encoded IgG immunoglobulin heavy chain allotype marker G2m(n). IgG antigliadin antibody was found in GSE patients with G2m(n) regardless of whether the HLA-B8 and/or-DR3 major histocompatibility complex antigens that occur frequently in GSE were present. No patient lacking G2m(n) had significant levels of antigliadin antibody. The association between antigliadin antibody and the immunoglobulin heavy chain allotype marker G2m(n) in GSE patients likely reflects the presence of Gmn-linked variable region genes or Gmn-linked genes that regulate variable region gene expression

Development of a Multiplex Single Base Extension Assay for Mitochondrial DNA Haplogroup Typing

Cilj Razviti test za brzo pretraživanje, kako bi se skratilo vrijeme testiranja i potrošnja uzorka pri određivanju haploskupina mitohondrijske DNA. Postupci U svrhu vrjednovanja testa ukupno je testirano 147 uzoraka, uključujući 73 uzorka kojima je uspješno određena haploskupina s pomoću tipizacije kontrolnog područja (engl. control region, CR) mitohondrijske DNA (mtDNA), 21 uzorak s nepotpuno tipiziranom haploskupinom na osnovi CR, i 31 uzorak poznatog nasljednog izvora kojima prethodno nije tipizirana haploskupina. Dodatno su s pomoću sustava mnogostruke analize kratkih jezgrenih polimorfnih odsječaka (engl., short nuclear polymorphism, SNP) analizirane dvije jako degradirane ljudske kosti zakopane krajem četrdeseetih godina prošloga stoljeća. Rezultati Kad je mnogostruki sustav SNP primijenjen za tipizaciju 96 uzoraka s prethodno sekvencioniranim CR, opaženo je povećanje definiranja haploskupine ili makrohaploskupine u odnosu na uobičajenu analizu slijeda CR. Prošireni test za pojedinačne baze uspješno je primijenjen u određivanju haploskupina iz uzoraka kostiju starih desetljećima, još iz II. Svjetskoga rata. Zaključak Mnogostruki sustav SNP uspješno je primijenjen za određivanje statusa haploskupina jako raspadnutih ljudskih kostiju, čime je pokazao sposobnost odstranjenja mogućih onečišćenja. Mnogostruki sustav SNP predstavlja jeftin a vrlo učinkovit postupak kojim se mogu tipizirati haploskupine mtDNA A, B, C, D, E, F, G, H, L1/L2, L3, M i N, što znači da se može dobro iskoristiti za brza pretraživanja pri identifikaciji ljudi ili u antropološkim istraživanjima.Aim To provide a screening tool to reduce time and sample consumption when attempting mitochondrial DNA (mtDNA) haplogroup typing. Methods A single base primer extension assay was developed to enable typing, in a single reaction, of twelve mtDNA haplogroup specific polymorphisms. For validation purposes a total of 147 samples were tested including 73 samples successfully haplogroup typed using mtDNA control region (CR) sequence data, 20 samples inconclusively haplogroup typed by CR sequence data, 21 samples previously haplogroup typed using restriction fragment length polymorphism (RFLP) analysis, and 31 samples of known ancestral origin without previous haplogroup typing. Additionally, two highly degraded human bones embalmed and buried in the early 1950s were analyzed using the single nucleotide polymorphisms (SNP) multiplex. Results When the SNP multiplex was used to type the 96 previously CR sequenced specimens, an increase in haplogroup or macrohaplogroup assignment relative to conventional CR sequence analysis was observed. The single base extension assay was also successfully used to assign a haplogroup to decades-old, embalmed skeletal remains dating to World War II. Conclusion The SNP multiplex was successfully used to obtain haplogroup status of highly degraded human bones, and demonstrated the ability to eliminate possible contributors. The SNP multiplex provides a low-cost, high throughput method for typing of mtDNA haplogroups A, B, C, D, E, F, G, H, L1/L2, L3, M, and N that could be useful for screening purposes for human identification efforts and anthropological studies

Immunoglobulin Allotypes among Taiwan Aborigines: Evidence of Malarial Selection Could Affect Studies of Population Affinity

The aborigines of Taiwan represent the indigenous inhabitants of the island at the time of the arrival of the Chinese from the mainland. Linguistically, the aboriginal Taiwanese are related to the Malayo-Polynesianspeaking inhabitants of Indonesia and the Philippines. Three tribes occupied lowland areas while six tribes occupied highland areas. Previous studies indicate that genetic markers associated with malaria occur in lowland populations. Though the GM haplotypes are demonstrated to be very useful in the measure of population affinities, the possibility of malarial selection on this locus could affect studies of population affinity. The present work is a case study to see whether a subdivided insular population under a possible selective load will provide divergent clustering analysis depending on the population sampled. Immunoglobulin allotype (GM and KM) profiles were generated on 230 lowland and 407 highland Taiwan Aborigines from the nine tribes. Ahighly significant difference in GM haplotype distribution was detected between lowland and highland populations (adjusted G = 69.408, 2 df [degrees of freedom], p \u3c 0.00001). There were no significant differences in KM*1 frequency by altitude. The Taiwan Aboriginal GM and KM frequencies were compared to data from Indonesians, Vietnamese, Thai, Malay, Chinese from Taiwan, and Ryukyu Islanders from Okinawa using cluster analysis. The lowland populations plot among the Thai (N, NC) and Malayan Aborigines. In contrast, the highland and total Taiwan Aborigine samples plot with the Indonesian, Vietnamese, and Malayan Negrito samples. Thus, depending on the populations of Taiwan Aborigines used, different conclusions could be reached. The highland population supports the published linguistic ties; however, the lowland population does not support the linguistic relationship with Indonesian populations but is more closely related to Thai and Malays, or reflects a similar selection history