Over the last 35 years, researchers from the Laboratory of Biological Anthropology at the University of Kansas have been working with Mennonite communities to better understand evolutionary patterns of fission-fusion in relationship to their genetic history and population structure. In this study, short tandem repeat (STR) markers from the nonrecombining region of the Y chromosome (NRY) provided increased resolution of the molecular population structure for these groups. NRY is known to be informative for determining paternal genetic ancestral patterns in recently derived human populations. Mennonites represent a branch of the Anabaptist movement that began in northern and central Europe in the 16th century and maintain a well-documented migration and genealogical history. Provided this historical information, we investigated the genetic relationship of 15 NRY STR loci within five Mennonite communities from Kansas (Goessel, Lone Tree, Garden View, and Meridian) and Nebraska (Henderson). We sought to determine if patterns of fission/fusion along familial lines persisted with paternal genetic information as evidenced through other classical genetic polymorphisms and molecular markers. NRY haplotype information was obtained for 94 individuals, and genetic variation was analyzed and compared across the five study populations and comparative Anabaptist and European populations. NRY haplogroups were assigned using a Bayesian allele frequency approach with 14 STR loci. A total of 92 NRY haplotypes were detected, with none shared across these communities. The most prevalent NRY haplogroup was R1b, which occurred in 56% of the entire sample. Eight additional NRY haplogroups (E1b1b, G2a, I1, I2, J2a1, L, Q, and R1a) were detected in smaller frequencies. Principal component analysis of NRY data, in contrast to mitochondrial DNA data, displayed no patterns of population subdivision of these congregations into communities. These NRY genetic profiles provide additional information regarding the recent migratory history of Mennonite communities and additional evidence for fission along paternal lines after migration to the United States.

Large-scale genotyping and next-generation sequencing techniques have allowed great advances in the field of molecular genetics. Numerous common variants of low impact have been associated with many complex human traits and diseases, such as bipolar disorder and schizophrenia. Although they may exert a greater impact on risk, few rare disease variants have been found, owing to the greatly increased sample sizes that are typically necessary to demonstrate association with rarer variants. One alternative strategy is to study isolated populations, where historical bottlenecks reduce genetic diversity and some otherwise rare variants may drift to higher frequencies. Here we describe the Mennonite population settlements, considering their history of multiple bottlenecks followed by demographic expansion and a currently widespread geographical distribution. We argue that Mennonite populations are valuable partners for studies seeking genetic variants that exert a high impact on risk for a variety of common disorders, including mental illnesses.

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.

Maya civilization developed in Mesoamerica and encompassed the Yucatan Peninsula, Guatemala, Belize, part of the Mexican states of Tabasco and Chiapas, and the western parts of Honduras and El Salvador. This civilization persisted approximately 3,000 years and was one of the most advanced of its time, possessing the only known full writing system at the time, as well as art, sophisticated architecture, and mathematical and astronomical systems. This civilization reached the apex of its power and influence during the Preclassic period, from 2000 BCE to 250 CE. Genetic variation in the pre-Hispanic Mayas from archaeological sites in the Mexican states of Yucatan, Chiapas, Quintana Roo, and Tabasco and their relationship with the contemporary communities in these regions have not been previously studied. Consequently, the principal aim of this study was to determine mitochondrial DNA (mtDNA) variation in the pre-Hispanic Maya population and to assess the relationship of these individuals with contemporary Mesoamerican Maya and populations from Asia, Beringia, and North, Central, and South America. Our results revealed interactions and gene flow between populations in the different archaeological sites assessed in this study. The mtDNA haplogroup frequency in the pre-Hispanic Maya population (60.53%, 34.21%, and 5.26% for haplogroups A, C, and D, respectively) was similar to that of most Mexican and Guatemalan Maya populations, with haplogroup A exhibiting the highest frequency. Haplogroup B most likely arrived independently and mixed with populations carrying haplogroups A and C based on its absence in the pre-Hispanic Mexican Maya populations and low frequencies in most Mexican and Guatemalan Maya populations, although this also may be due to drift. Maya and Ciboneys sharing haplotype H10 belonged to haplogroup C1 and haplotype H4 of haplogroup D, suggesting shared regional haplotypes. This may indicate a shared genetic ancestry, suggesting more regional interaction between populations in the circum-Caribbean region than previously demonstrated. Haplotype sharing between the pre-Hispanic Maya and the indigenous populations from Asia, the Aleutian Islands, and North, Central, and South America provides evidence for gene flow from the ancestral Amerindian population of the pre-Hispanic Maya to Central and South America.

The Rama are a coastal population from southern Nicaragua who in large part were able to resist, at least for a time, the cultural changes and social reorganization brought on by colonial and modern influences. Historical information leaves the Rama origins and biological relationships with nearby extinct and extant groups ambiguous. The objective of this study was to examine the internal genetic microdifferentiation based on the first hypervariable region of the mitochondrial DNA (mtDNA) from a sample of approximately 20% of the population, and to expand the few available historical and anthropological data on the Rama by exploring the effects of cultural practices and historical events on genetic structure, providing an integrative perspective on the Rama genetic history. When considering differences in the spatial distribution and genetic diversity of the mtDNA haplotypes together with historical information on the Rama, a noteworthy pattern emerges. (a) Haplotypes are differentially distributed among a central Rama community (Punta Águila) compared with the other five peripheral communities (analysis of molecular variance: F_CT = 0.10, p < 0.001), and their distribution is consistent with the historical relocation of this population after their split from Punta Gorda in the 18th century. (b) Differential genetic signatures found among central and peripheral Rama communities resemble two population histories: one of stability (haplogroup A2) and other of expansion (haplogroup B2), supporting the possibility that these patterns of genetic microdifferentiation between central and peripheral populations resulted from the 18th-century unification in southern Nicaragua of the Rama and a group of Voto migrants from Costa Rica that later split off and moved to the Bay of Bluefields.