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BACKGROUND: The etiology of alcoholism and alcohol abuse, like many other complex diseases, is heterogeneous and multifactorial. Numerous studies demonstrate a genetic contribution to variation in the expression of alcohol-related disorders in humans. Over the past decade, nonhuman primates have emerged as a valuable model for some aspects of human alcohol abuse because of their phylogenetic proximity to humans. Long-term, longitudinal studies of rhesus macaques (Macaca mulatta) have provided much insight into environmental influences, especially early life experiences, on alcohol consumption and behavior patterns that characterize alcohol intake later in life. It is not known, however, whether there is a genetic component as well to the variation seen in alcohol consumption in rhesus macaques. A significant genetic component to variation in alcohol consumption in rhesus macaques would show for the first time that like humans, for nonhuman primates additive genetic influences are important. Moreover, their use as a model for alcohol-related disorders in humans would have even greater relevance and utility for designing experiments incorporating the expanding molecular genetics field, and allow researchers to investigate the interaction among the known environmental influences and various genotypes. METHODS: In this study, we investigate factors contributing to variation in alcohol consumption of 156 rhesus macaques collected over 10 years when subjects were adolescent in age, belonging to a single extended pedigree, with each cohort receiving identical early rearing backgrounds and subsequent treatments. To measure alcohol consumption each animal was provided unfettered simultaneous access both to an aspartame-sweetened 8.4% (v/v) alcohol-water solution, the aspartame-sweetened vehicle, and to water for 1 hour each day during the early afternoon between 13:00 and 15:00 in their home cages for a period of 5 to 7 weeks. We use multiple regression to identify factors that significantly affect alcohol consumption among these animals and a maximum likelihood program (ASReml) that, controlling for the significant factors, estimates the genetic contribution to the variance in alcohol consumption. RESULTS: Multiple regression analysis identified test cohort and rearing environment as contributing to 57 and 2%, respectively, of the total variance in alcohol consumption. Of the remaining 41% of the variance about half (19.8%) was attributable to additive genetic effects using a maximum likelihood program. CONCLUSION: This study demonstrates that, as in humans, there are additive genetic factors that contribute to variation in alcohol consumption in rhesus macaques, with other nongenetic factors accounting for substantial portions of the variance in alcohol consumption, Our findings show the presence of an additive genetic component and suggest the potential utility of the nonhuman primate as a molecular genetics tool for understanding alcohol abuse and alcoholism. [ABSTRACT FROM AUTHOR]

Little is known regarding the first people to enter the Americas and their genetic legacy. Genomic analysis of the oldest human remains from the Americas showed a direct relationship between a Clovis-related ancestral population and all modern Central and South Americans as well as a deep split separating them from North Americans in Canada. We present 91 ancient human genomes from California and Southwestern Ontario and demonstrate the existence of two distinct ancestries in North America, which possibly split south of the ice sheets. A contribution from both of these ancestral populations is found in all modern Central and South Americans. The proportions of these two ancestries in ancient and modern populations are consistent with a coastal dispersal and multiple admixture events., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Objective: Vervet monkeys are common in most tree-rich areas of South Africa, but their absence from grassland and semi-desert areas of the country suggest potentially restricted and mosaic local population patterns that may have relevance to local phenotype patterns and selection. A portion of the mitochondrial DNA control region was sequenced to study patterns of genetic differentiation., Methods: DNA was extracted, and mitochondrial DNA sequences were obtained from 101 vervet monkeys at 15 localities, which represent both an extensive (widely across the distribution range) and intensive (more than one troop at most of the localities) sampling strategy. Analyses utilized Arlequin 3.1, MEGA 6, BEAST v1.5.2, and Network V3.6.1., Results: The dataset contained 26 distinct haplotypes, with six populations fixed for single haplotypes. Pairwise P-distance among population pairs showed significant differentiation among most population pairs, but with nonsignificant differences among populations within some regions. Populations were grouped into three broad clusters in a maximum likelihood phylogenetic tree and a haplotype network. These clusters correspond to i) north-western, northern, and north-eastern parts of the distribution range as well as the northern coastal belt; ii) central areas of the country; and iii) southern part of the Indian Ocean coastal belt and adjacent inland areas., Conclusions: Apparent patterns of genetic structure correspond to current and past distribution of suitable habitat, geographic barriers to gene flow, geographic distance, and female philopatry. However, further work on nuclear markers and other genomic data are necessary to confirm these results., (© 2015 Wiley Periodicals, Inc.)

Vervet monkeys (Chlorocebus aethiops) often live in close proximity to humans. Vervets are known to raid crops, homes and gardens in suburban areas leading to human-vervet conflict. In general, primate groups with access to human foods experience increased population densities and intra-group aggression. This suggests high stress loads for vervets living in environments with high levels of human habitat disturbance and close proximity to humans. We tested the hypothesis that populations characterized by high levels of human impact are more physiologically stressed than low human impact populations, and that this increased stress would be reflected in higher concentrations of hair cortisol. We predicted that because females would be less likely to engage in high risk foraging activities, and hence keep more distance from humans than males, their hair cortisol levels should be lower than those in males. We quantified cortisol in the hair of wild caught individuals from populations that experienced different degrees of human habitat disturbance and differences in access to human food. We found that males in high human impact groups had significantly higher hair cortisol concentrations than those in low human impact groups, although this difference was not observed in female vervets. Human impacts on vervet behavioral ecology appear to be a significant source of stress for male animals in particular.

This study seeks to understand how humans impact the dietary patterns of eight free-ranging vervet monkey (Chlorocebus pygerythrus) groups in South Africa using stable isotope analysis. Vervets are omnivores that exploit a wide range of habitats including those that have been anthropogenically-disturbed. As humans encroach upon nonhuman primate landscapes, human-nonhuman primate interconnections become increasingly common, which has led to the rise of the field of ethnoprimatology. To date, many ethnoprimatological studies have examined human-nonhuman primate associations largely in qualitative terms. By using stable carbon (δ13C) and nitrogen (δ15N) isotope analysis, we use quantitative data to understand the degree to which humans impact vervet monkey dietary patterns. Based on initial behavioral observations we placed the eight groups into three categories of anthropogenic disturbance (low, mid, and high). Using δ13C and δ15N values we estimated the degree to which each group and each anthropogenically-disturbed category was consuming C4 plants (primarily sugar cane, corn, or processed foods incorporating these crops). δ13C values were significantly different between groups and categories of anthropogenic-disturbance. δ15N values were significantly different at the group level. The two vervet groups with the highest consumption of C4 plants inhabited small nature reserves, appeared to interact with humans only sporadically, and were initially placed in the mid level of anthropogenic-disturbance. However, further behavioral observations revealed that the high δ13C values exhibited by these groups were linked to previously unseen raiding of C4 crops. By revealing these cryptic feeding patterns, this study illustrates the utility of stable isotopes analysis for some ethnoprimatological questions.

Vervet monkeys (Chlorocebus aethiops) exhibit bright blue scrotal skin which may function to mediate social interactions by acting as a socio-sexual signal. Previous research on scrotal coloration among vervet monkeys was limited to experimental work on captive Ch. a. sabaeus, the least colorful vervet subspecies, and two field studies of the more colorful Ch. a. pygerythrus. In a study of free-ranging and captive vervet monkeys in South Africa (Ch. pygerythrus), West Africa (Ch. a. sabaeus) and the Caribbean (Ch. a. sabaeus), we examined scrotal color variation across geographically distant subspecies. We provide an exploration of how digital photographs may be used to quantify and analyze blue and green skin coloration by examining the blue-yellow opponency channel and luminance channel as color measures. We found that that at all ages the scrotal color of Ch. a. pygerythrus males was always bluer and darker than that of Ch. a. sabaeus males. Among Ch. a. pygerythrus scrotal color becomes bluer and lightens with increasing age, while the color of Ch. a. sabaeus males also lightens, but becomes less blue with increasing age. We suggest that color variation is related to maturation and may function as an age-related signal among Ch. a. pygerythrus and Ch. a. sabaeus. We also found color was related to three morphological features among adults. For Ch. a. pygerythrus, higher body weight is associated with more blue color and longer canine length is associated with lighter color. Lighter color was associated with longer body lengths among Ch. a. sabaeus. Future studies focused on color variation within age classes are needed to examine the potential signal content of color in this species., (© 2013 Wiley Periodicals, Inc.)

Cryptic and endangered fauna, including many primate taxa, pose challenges for noninvasive collection of biomaterials. As a result, application of noninvasive genotyping to primates has been limited to the use of samples such as feces and hair for the extraction of PCR-amplifiable DNA. We present a method for noninvasive collection of saliva from habituated, free-ranging monkeys. The method utilizes a low-cost apparatus that controls for contamination and is usable with individual, free-ranging primates. Saliva samples were collected from 18 individuals in a population of Tibetan macaques (Macaca thibetana) in the Valley of Wild Monkeys in Huangshan, People's Republic of China. DNA was extracted from these samples and PCR-amplified for both mitochondrial and nuclear genes, Cytochrome B and MHC-DR Beta 1, respectively. These results indicate this is an effective technique for the noninvasive collection of saliva across age and sex class, and dominance rank in a free-ranging, terrestrial primate species. This device could have wide application for obtaining high-quality saliva samples from free-ranging primate populations for use in epidemiological studies, hormonal analyses of HPA axis function, pathogen screening, noninvasive genotyping, and behavioral genetics., (© 2012 Wiley Periodicals, Inc.)

Objectives: Global patterns of the incidence of cancer are often attributed to environmental and lifestyle differences between regions. Less attention has been given to global patterns of allelic variation of genes that may contribute to the risk of developing cancer., Methods: We genotyped samples from 21 populations for four variants of the progesterone receptor (PR) gene. One is an Alu insertion in intron 7 which defines the PROGINS haplotype. The others include a promoter region SNP 331+ G/A (rs10895068), a haplotype defining T/C substitution in intron 6 (rs561650), and an A/T substitution (rs608995) in the 3' untranslated region of the gene. All variants have been investigated elsewhere in association with female reproductive cancers in western populations., Results: We found population differences in the frequency of each of these alleles across study populations (P < 0.01, log-likelihood G statistic, computed in FSTAT) and therefore examined the correlation between the frequency of each genetic variant and the incidence of three female reproductive cancers (breast, uterine, and ovarian) obtained from the Globocan 2008 database. Breast and ovarian cancer incidence were significantly correlated with the frequency of the Alu insertion (r = 0.86 and 0.53) and the +331 A variant (r = 0.57 and 0.73)., Conclusions: Our data expand the information on genetic variation at the PR locus in non-western populations and support an argument for more work on the genetic epidemiology of cancer among nonwestern populations., (2011 Wiley Periodicals, Inc.)

Western lowland gorillas (Gorilla gorilla gorilla) are designated as critically endangered and wild populations are dramatically declining as a result of habitat destruction, fragmentation, diseases (e.g., Ebola) and the illegal bushmeat trade. As wild populations continue to decline, the genetic management of the North American captive western lowland gorilla population will be an important component of the long-term conservation of the species. We genotyped 26 individuals from the North American captive gorilla collection at 11 autosomal microsatellite loci in order to compare levels of genetic diversity to wild populations, investigate genetic signatures of a population bottleneck and identify the genetic structure of the captive-born population. Captive gorillas had significantly higher levels of allelic diversity (t(7) = 4.49, P = 0.002) and heterozygosity (t(7) = 4.15, P = 0.004) than comparative wild populations, yet the population has lost significant allelic diversity while in captivity when compared to founders (t(7) = 2.44, P = 0.04). Analyses suggested no genetic evidence for a population bottleneck of the captive population. Genetic structure results supported the management of North American captive gorillas as a single population. Our results highlight the utility of genetic management approaches for endangered nonhuman primate species.

We report a sampling strategy based on Mendelian Breeding Units (MBUs), representing an interbreeding group of individuals sharing a common gene pool. The identification of MBUs is crucial for case-control experimental design in association studies. The aim of this work was to evaluate the possible existence of bias in terms of genetic variability and haplogroup frequencies in the MBU sample, due to severe sample selection. In order to reach this goal, the MBU sampling strategy was compared to a standard selection of individuals according to their surname and place of birth. We analysed mitochondrial DNA variation (first hypervariable segment and coding region) in unrelated healthy subjects from two different areas of Sardinia: the area around the town of Cabras and the western Campidano area. No statistically significant differences were observed when the two sampling methods were compared, indicating that the stringent sample selection needed to establish a MBU does not alter original genetic variability and haplogroup distribution. Therefore, the MBU sampling strategy can be considered a useful tool in association studies of complex traits.

Mitochondrial and Y-chromosome DNA were analyzed from 10,300-year-old human remains excavated from On Your Knees Cave on Prince of Wales Island, Alaska (Site 49-PET-408). This individual's mitochondrial DNA (mtDNA) represents the founder haplotype of an additional subhaplogroup of haplogroup D that was brought to the Americas, demonstrating that widely held assumptions about the genetic composition of the earliest Americans are incorrect. The amount of diversity that has accumulated in the subhaplogroup over the past 10,300 years suggests that previous calibrations of the mtDNA clock may have underestimated the rate of molecular evolution. If substantiated, the dates of events based on these previous estimates are too old, which may explain the discordance between inferences based on genetic and archaeological evidence regarding the timing of the settlement of the Americas. In addition, this individual's Y-chromosome belongs to haplogroup Q-M3*, placing a minimum date of 10,300 years ago for the emergence of this haplogroup.

The Integrated Primate Biomaterials and Information Resource (www.IPBIR.org) provides essential research reagents to the scientific community by establishing, verifying, maintaining, and distributing DNA and RNA derived from primate cell cultures. The IPBIR uses mitochondrial cytochrome c oxidase subunit I sequences to verify the identity of samples for quality control purposes in the accession, cell culture, DNA extraction processes and prior to shipping to end users. As a result, IPBIR is accumulating a database of 'DNA barcodes' for many species of primates. However, this quality control process is complicated by taxon specific patterns of 'universal primer' failure, as well as the amplification or co-amplification of nuclear pseudogenes of mitochondrial origins. To overcome these difficulties, taxon specific primers have been developed, and reverse transcriptase PCR is utilized to exclude these extraneous sequences from amplification. DNA barcoding of primates has applications to conservation and law enforcement. Depositing barcode sequences in a public database, along with primer sequences, trace files and associated quality scores, makes this species identification technique widely accessible. Reference DNA barcode sequences should be derived from, and linked to, specimens of known provenance in web-accessible collections in order to validate this system of molecular diagnostics.

This study examines the mtDNA diversity of the proposed descendants of the multiethnic Hohokam and Anasazi cultural traditions, as well as Uto-Aztecan and Southern-Athapaskan groups, to investigate hypothesized migrations associated with the Southwest region. The mtDNA haplogroups of 117 Native Americans from southwestern North America were determined. The hypervariable segment I (HVSI) portion of the control region of 53 of these individuals was sequenced, and the within-haplogroup diversity of 18 Native American populations from North, Central, and South America was analyzed. Within North America, populations in the West contain higher amounts of diversity than in other regions, probably due to a population expansion and high levels of gene flow among subpopulations in this region throughout prehistory. The distribution of haplogroups in the Southwest is structured more by archaeological tradition than by language. Yumans and Pimans exhibit substantially greater genetic diversity than the Jemez and Zuni, probably due to admixture and genetic isolation, respectively. We find no evidence of a movement of mtDNA lineages northward into the Southwest from Central Mexico, which, in combination with evidence from nuclear markers, suggests that the spread of Uto-Aztecan was facilitated by predominantly male migration. Southern Athapaskans probably experienced a bottleneck followed by extensive admixture during the migration to their current homeland in the Southwest., (Copyright 2003 Wiley-Liss, Inc.)

The mitochondrial DNA haplogroups and hypervariable segment I (HVSI) sequences of 1,612 and 395 Native North Americans, respectively, were analyzed to identify major prehistoric population events in North America. Gene maps and spatial autocorrelation analyses suggest that populations with high frequencies of haplogroups A, B, and X experienced prehistoric population expansions in the North, Southwest, and Great Lakes region, respectively. Haplotype networks showing high levels of reticulation and high frequencies of nodal haplotypes support these results. The haplotype networks suggest the existence of additional founding lineages within haplogroups B and C; however, because of the hypervariability exhibited by the HVSI data set, similar haplotypes exhibited in Asia and America could be due to convergence rather than common ancestry. The hypervariability and reticulation preclude the use of estimates of genetic diversity within haplogroups to argue for the number of migrations to the Americas.

Nonhuman primates offer unique opportunities to study the effects of genes, environments, and their interaction, on physiology and complex behavior. We examined genotype and early environment contributions to CNS function in a large sample of rhesus monkeys. In humans, length variation of the serotonin (5-HT) transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) that results in allelic variation in 5-HTT expression is associated with decreased serotonergic function and 5-HT-mediated psychopathology. We report that an analogous variation of the gene's regulatory region in monkeys interacts with early experience to affect central 5-HT functioning. Monkeys with deleterious early rearing experiences were differentiated by genotype in cerebrospinal fluid concentrations of the 5-HT metabolite, 5-hydroxyindoleacetic acid, while monkeys reared normally were not. These findings demonstrate an environment-dependent effect of the rh5-HTTLPR genotype on CNS 5-HT function and suggest nonhuman primates may provide an important avenue for investigating gene/environment interactions using candidate genes for physiological and behavioral traits.

We studied the allelic and genotypic distribution of the major histocompatibility class-II locus DQA1 observed in a random sample of Indian rhesus macaques (Macaca mulatta) from a major breeding facility in the United States. The DNA was isolated from whole blood samples collected between 1991 and 1994 from 65 Indian rhesus monkeys. Polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP), which involves use of specific amplification of DQA1 exon 2 and subsequent restriction digestion of the 242-base pair fragment, was used to genotype the animals for the 20 known macaque (Mamu)-DQA1 alleles. Frequencies for four alleles (DQA1*240x, *2502, *2503 and *0102) differed significantly from those reported in a smaller sample of rhesus macaques from the German Primate Center. The modest genetic survey of Mamu-DQA1 genotypes presented here will be particularly useful in designing epidemiologic studies that investigate associations between immunogenetic background and disease susceptibility in macaque models of human disease.

Background: The purpose of this study was to assess the impact of early rearing and stress-induced rise of plasma cortisol collected during infancy as a biological predictors of adult alcohol consumption in nonhuman primates., Methods: Ninety-seven female and male rhesus macaques (Macaca mulatta) were investigated. They were reared for their first 6 months of life either without mothers or other adults but with constant access to same-aged peers (peer-reared), or as controls with their mothers (mother-reared). When subjects reached 6 months of age, they underwent a series of four sequential weeks of 4-day social separations. Blood was drawn 1 and 2 hr after initiation of the 4-day separation periods, and the plasma was assayed for plasma cortisol concentrations. When the subjects were young adults (approximately 50 months of age), they were tested for voluntary intake of alcohol for 1 hr per day, 4 days a week, during a period of 5 to 7 weeks under normal living conditions., Results: The social separation challenge increased infant plasma cortisol concentrations, with peer-reared subjects exhibiting higher stress-induced cortisol concentrations than mother-reared animals. Subjects that responded to the social separation challenge with high cortisol levels consumed significantly more alcohol per kilogram of body weight as adults than subjects with a low cortisol response to the separation challenge, regardless of rearing condition. In addition, male and peer-reared subjects consumed significantly more alcohol than female and mother-reared subjects, respectively., Conclusions: These findings suggest that early rearing experiences, such as adult absence, and high plasma cortisol concentrations early in life after a social separation stressor, are useful psychobiological predictors of future high alcohol consumption among nonhuman primates.

Mitochondrial DNA (mtDNA) samples of 70 Native Americans, most of whom had been found not to belong to any of the four common Native American haplogroups (A, B, C, and D), were analyzed for the presence of Dde I site losses at np 1715 and np 10394. These two mutations are characteristic of haplogroup X which might be of European origin. The first hypervariable segment (HVSI) of the non-coding control region (CR) of mtDNA of a representative selection of samples exhibiting these mutations was sequenced to confirm their assignment to haplogroup X. Thirty-two of the samples exhibited the restriction site losses characteristic of haplogroup X and, when sequenced, a representative selection (n = 11) of these exhibited the CR mutations commonly associated with haplogroup X, C --> T transitions at np 16278 and 16223, in addition to as many as three other HVSI mutations. The wide distribution of this haplogroup throughout North America, and its prehistoric presence there, are consistent with its being a fifth founding haplogroup exhibited by about 3% of modern Native Americans. Its markedly nonrandom distribution with high frequency in certain regions, as for the other four major mtDNA haplogroups, should facilitate establishing ancestor/descendant relationships between modern and prehistoric groups of Native Americans. The low frequency of haplogroups other than A, B, C, D, and X among the samples studied suggests a paucity of both recent non-Native American maternal admixture in alleged fullblood Native Americans and mutations at the restriction sites that characterize the five haplogroups as well as the absence of additional (undiscovered) founding haplogroups., (Copyright 1999 Wiley-Liss, Inc.)

The distributions of mtDNA diversity within and/or among North American haplogroups, language groups, and tribes were used to characterize the process of tribalization that followed the colonization of the New World. Approximately 400 bp from the mtDNA control region of 1 Na-Dene and 33 Amerind individuals representing a wide variety of languages and geographic origins were sequenced. With the inclusion of data from previous studies, 225 native North American (284 bp) sequences representing 85 distinct mtDNA lineages were analyzed. Mean pairwise sequence differences between (and within) tribes and language groups were primarily due to differences in the distribution of three of the four major haplogroups that evolved before settlement of the New World. Pairwise sequence differences within each of these three haplogroups were more similar than previous studies based on restriction enzyme analysis have indicated. The mean of pairwise sequence differences between Amerind members of haplogroup A, the most common of the four haplogroups in North America, was only slightly higher than that for the Eskimo, providing no evidence of separate ancestry, but was about two-thirds higher than that for the Na-Dene. However, analysis of pairwise sequence divergence between only tribal-specific lineages, unweighted for sample size, suggests that random evolutionary processes have reduced sequence diversity within the Na-Dene and that members of all three language groups possess approximately equally diverse mtDNA lineages. Comparisons of diversity within and between specific ethnic groups with the largest sample size were also consistent with this outcome. These data are not consistent with the hypothesis that the New World was settled by more than a single migration. Because lineages tended not to cluster by tribe and because lineage sharing among linguistically unrelated groups was restricted to geographically proximate groups, the tribalization process probably did not occur soon after settlement of the New World, and/or considerable admixture has occurred among daughter populations.

The mtDNA of most Native Americans has been shown to cluster into four lineages, or haplogroups. This study provides data on the haplogroup affiliation of nearly 500 Native North Americans including members of many tribal groups not previously studied. Phenetic cluster analysis shows a fundamental difference among 1) Eskimos and northern Na-Dene groups, which are almost exclusively mtDNA haplogroup A, 2) tribes of the Southwest and adjacent regions, predominantly Hokan and Uto-Aztecan speakers, which lack haplogroup A but exhibit high frequencies of haplogroup B, 3) tribes of the Southwest and Mexico lacking only haplogroup D, and 4) a geographically heterogeneous group of tribes which exhibit varying frequencies of all four haplogroups. There is some correspondence between language group affiliations and the frequencies of the mtDNA haplogroups in certain tribes, while geographic proximity appears responsible for the genetic similarity among other tribes. Other instances of similarity among tribes suggest hypotheses for testing with more detailed studies. This study also provides a context for understanding the relationships between ancient and modern populations of Native Americans.

The deletion of a 9-bp segment from the intergenic region between the mtDNA cytochrome oxidase II gene and the lysine tRNA gene has been documented mainly in individuals of East Asian ancestry and in individuals from East Asian-derived populations (e.g., Polynesia). Among Native Americans the deletion is absent among Eskimos and northern Na-Dene populations and present among most Amerind populations [sensu Greenberg (1987); i.e., all Native Americans except Eskimo-Aleut and Na-Dene] that have been studied. To better characterize the frequency and distribution of the 9-bp deletion in North America, we surveyed more than 400 individuals from 59 tribes representing a variety of linguistic groups. The absence of the deletion among Eskimo and northern Na-Dene populations is confirmed. Among Amerind groups the deletion is present in all groups represented by more than six individuals. The geographic distribution of the frequencies of the deletion appears to be clinal in North America. The deletion is absent in the Artic and Subartic and reaches its highest frequency in the Southwest. This distribution is consistent with the hypothesis that the ancestors of the Amerinds and Na-Dene arrived in the New World by means of separate migrations. The presence of the 9-bp deletion in high frequencies in all the major linguistic groups in the Southwest suggests that migration among tribes was common.