Cecilia Penedo

Genetics, Molecular Biology
37.96

Publications

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    ABSTRACT: Within the United States (US), Peninsular bighorn sheep (Ovis canadensis nelsoni, PBS) are listed as federally endangered. Despite known metapopulation structure, little is known regarding functional connectivity across the international border with Mexico. Increasing threats to connectivity associated with highway expansion, renewable energy development, and completion of the US–Mexico border fence, led us to conduct a study of genetic variation and spatial structure. Blood and fecal samples were collected (n = 224) on both sides of the border from 1992 to 2013. Genetic data was obtained for 25 microsatellite loci and 515 base pairs of the mitochondrial DNA control region. Microsatellite diversity (observed heterozygosity = 0.56; allelic richness = 4.1; inbreeding coefficient = 0.01) was substantial despite past demographic declines. STRUCTURE analysis indicated the presence of three genetic populations, one of which spanned the international border. This pattern of genetic structure was supported by analysis of molecular variance for both microsatellites and mitochondrial DNA (P < 0.01), and low-moderate pairwise fixation indices (FST = 0.09–0.15; ΦST = 0.18–0.27) indicated substantial gene flow among populations. Migrant detection tests indicated natal dispersal occurred within both sexes, with no evidence of sex bias. Despite the severe reductions in population abundance which led to federal listing in the US, these data suggest PBS have retained substantial genetic variation and show little evidence of a recent genetic bottleneck. Patterns of genetic spatial structure indicate gene flow throughout the ranges is common, and construction of a US–Mexico border fence or wind energy infrastructure would disrupt connectivity of the metapopulation. Future conservation efforts should focus on identifying dispersal corridors and maintaining functional connectivity to facilitate recolonization of unoccupied habitat.
    Biological Conservation 04/2015; 184. DOI:10.1016/j.biocon.2015.01.006 · 4.04 Impact Factor
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    ABSTRACT: Preimplantation genetic diagnosis has great potential in the horse, but information on evaluation of equine embryo biopsy samples is limited. Blastocysts were biopsied using a Piezo drill and methods for whole-genome amplification (WGA) investigated. Results for 33 genetic loci were then compared between biopsy samples from in vitro-produced (IVP) and in vivo-recovered (VIV) blastocysts. Under the experimental conditions described, WGA using the Qiagen Repli-g Midi kit was more accurate than that using the Illustra Genomiphi V2 kit (98.2% vs 25.8%, respectively). Using WGA with the Qiagen kit, three biopsy samples were evaluated from each of eight IVP and 19 VIV blastocysts, some produced using semen from stallions carrying the genetic mutations associated with the diseases hereditary equine regional dermal asthenia (HERDA), hyperkalemic periodic paralysis (HYPP) or polysaccharide storage myopathy 1 (PSSM1). Three of 81 biopsy samples (3.7%) returned 95% overall accuracy in IVP and VIV embryos, and this technique is suitable for use in a clinical setting.
    Reproduction Fertility and Development 03/2015; DOI:10.1071/RD14419 · 2.58 Impact Factor
  • Michael S. Mooring, M. Cecilia T. Penedo
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    ABSTRACT: Accurate measures of fitness are important for both basic research on sexual selection and applied conservation actions to promote genetic diversity. For polygynous mammals, good estimates of male reproductive success are often critically important, but especially difficult to obtain. Because the genetic contribution of males is impossible to directly measure in the field, investigators have developed surrogate measures of fitness based on behavioral observations. Such measures are founded on the assumption that observed mating success can reliably predict reproductive success, yet only a few studies have been in a position to validate the accuracy of this assumption. We studied the bison herd at Fort Niobrara National Wildlife Refuge for 8 years, conducting intensive behavioral observations on breeding behavior during the rut (2003-2009) and collecting tissue samples of calves born the following year (2004-2010) for genetic paternity analysis. Our results reveal 2 major trends also observed in other studies: Estimates of mating success were positively correlated with reproductive success when we pooled the entire herd across age classes or years. However, copulatory success did a poor job of predicting the actual number of offspring sired by individual males. For example, 44% of observed matings did not result in the birth of offspring, and 60% of the copulations that did produce a calf did not accurately predict the sire bull. Generalized linear mixed model analysis revealed that observation of mating by a given bull in itself had no predictive power regarding likelihood of paternity, whereas total copulations per season, dominance status, and age of bull or dam significantly influenced the probability of siring offspring. Although use of behavioral data was unable to predict the sire for particular cows, it did give insights into patterns of reproductive success that use of genetic data alone could not provide, such as the role of alternate mating strategies and sperm competition for male reproductive success. We conclude that both behavioral and genetic measures of fitness are needed to understand sexual selection and meet the challenges faced by species of conservation concern.
    Journal of Mammalogy 10/2014; 95(5):913-924. DOI:10.1644/13-MAMM-A-209 · 2.23 Impact Factor
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    ABSTRACT: Coat colours and patterns are highly variable in cats and are determined mainly by several genes with Mendelian inheritance. A 2-bp deletion in agouti signalling protein (ASIP) is associated with melanism in domestic cats. Bengal cats are hybrids between domestic cats and Asian leopard cats (Prionailurus bengalensis), and the charcoal coat colouration/pattern in Bengals presents as a possible incomplete melanism. The complete coding region of ASIP was directly sequenced in Asian leopard, domestic and Bengal cats. Twenty-seven variants were identified between domestic and leopard cats and were investigated in Bengals and Savannahs, a hybrid with servals (Leptailurus serval). The leopard cat ASIP haplotype was distinguished from domestic cat by four synonymous and four non-synonymous exonic SNPs, as well as 19 intronic variants, including a 42-bp deletion in intron 4. Fifty-six of 64 reported charcoal cats were compound heterozygotes at ASIP, with leopard cat agouti (A(P) (be) ) and domestic cat non-agouti (a) haplotypes. Twenty-four Bengals had an additional unique haplotype (A2) for exon 2 that was not identified in leopard cats, servals or jungle cats (Felis chaus). The compound heterozygote state suggests the leopard cat allele, in combination with the recessive non-agouti allele, influences Bengal markings, producing a darker, yet not completely melanistic coat. This is the first validation of a leopard cat allele segregating in the Bengal breed and likely affecting their overall pelage phenotype. Genetic testing services need to be aware of the possible segregation of wild felid alleles in all assays performed on hybrid cats.
    Animal Genetics 08/2014; 45(6). DOI:10.1111/age.12206 · 2.21 Impact Factor
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    ABSTRACT: Background/Question/Methods Peninsular bighorn sheep (Ovis canadensis nelsoni, PBS) are a federally endangered metapopulation of desert bighorn sheep endemic to the Peninsular Ranges of southern California, extending to the U.S./Mexico border. This metapopulation declined to <300 animals prior to listing in 1999, and is currently managed within a series of recovery regions approximating ewe home range groups. The goal of this project was to examine genetic diversity and spatial structure within the metapopulation and determine the extent of gene flow among selected recovery regions. Genetic data was generated by amplifying 39 microsatellite loci and a 515 bp fragment of the mtDNA control region from blood samples collected from sheep (n= 165) captured in seven recovery regions from 1992 to 2013. Results/Conclusions STRUCTURE analysis of microsatellite genotypes clustered sheep into two distinct genetic groups (north vs. south). Significant pairwise FST estimates among sheep from seven recovery regions (0.03 to 0.12) generally supported the presence of two genetic groups, with the possibility of additional substructure in the north (pairwise FST = 0.03 to 0.04, amova P = 0.02). Mitochondrial DNA analyses revealed five distinct haplotypes and indicated a similar pattern of north vs. south population structure (pairwise ΦST = 0.27 to 0.50). Considerable microsatellite diversity was found within both northern and southern groups (mean HO = 0.496; allelic richness = 3.47; FIS = 0.02), comparable to published accounts for desert bighorn sheep in other regions. We identified first-generation migrants of both sexes using GENECLASS2, but significantly lower assignment indices (AIc) among rams (Mann-Whitney U-test: P < 0.01) suggested dispersal was primarily male biased. Despite past population declines and ongoing deterministic threats, PBS have retained substantial genetic variation and gene flow among regions. Future conservation efforts should not only focus on sustaining population numbers, but also maintaining functional connectivity so the recovering metapopulation can expand into available habitat throughout the Peninsular Ranges.
    99th ESA Annual Convention 2014; 08/2014
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    ABSTRACT: For centuries, domestic horses have represented an important means of transport and served as working and companion animals. Although their role in transportation is less important today, many horse breeds are still subject to intense selection based on their pattern of locomotion. A striking example of such a selected trait is the ability of a horse to perform additional gaits other than the common walk, trot and gallop. Those could be four-beat ambling gaits, which are particularly smooth and comfortable for the rider, or pace, used mainly in racing. Gaited horse breeds occur around the globe, suggesting that gaitedness is an old trait, selected for in many breeds. A recent study discovered that a nonsense mutation in DMRT3 has a major impact on gaitedness in horses and is present at a high frequency in gaited breeds and in horses bred for harness racing. Here, we report a study of the worldwide distribution of this mutation. We genotyped 4396 horses representing 141 horse breeds for the DMRT3 stop mutation. More than half (2749) of these horses also were genotyped for a SNP situated 32 kb upstream of the DMRT3 nonsense mutation because these two SNPs are in very strong linkage disequilibrium. We show that the DMRT3 mutation is present in 68 of the 141 genotyped horse breeds at a frequency ranging from 1% to 100%. We also show that the mutation is not limited to a geographical area, but is found worldwide. The breeds with a high frequency of the stop mutation (>50%) are either classified as gaited or bred for harness racing. Introduction Few animals have been of such great value to humans as horses when it comes to means of transportation. All over the world, horses have been used for everyday transporta-tion, in military settings, cattle herding and agricultural power, pulling carriages and carts, pleasure riding or racing. Over the centuries, horse populations and breeds
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    ABSTRACT: For centuries, domestic horses have represented an important means of transport and served as working and companion animals. Although their role in transportation is less important today, many horse breeds are still subject to intense selection based on their pattern of locomotion. A striking example of such a selected trait is the ability of a horse to perform additional gaits other than the common walk, trot and gallop. Those could be four-beat ambling gaits, which are particularly smooth and comfortable for the rider, or pace, used mainly in racing. Gaited horse breeds occur around the globe, suggesting that gaitedness is an old trait, selected for in many breeds. A recent study discovered that a nonsense mutation in DMRT3 has a major impact on gaitedness in horses and is present at a high frequency in gaited breeds and in horses bred for harness racing. Here, we report a study of the worldwide distribution of this mutation. We genotyped 4396 horses representing 141 horse breeds for the DMRT3 stop mutation. More than half (2749) of these horses also were genotyped for a SNP situated 32 kb upstream of the DMRT3 nonsense mutation because these two SNPs are in very strong linkage disequilibrium. We show that the DMRT3 mutation is present in 68 of the 141 genotyped horse breeds at a frequency ranging from 1% to 100%. We also show that the mutation is not limited to a geographical area, but is found worldwide. The breeds with a high frequency of the stop mutation (>50%) are either classified as gaited or bred for harness racing.
    Animal Genetics 01/2014; 45(2). DOI:10.1111/age.12120 · 2.21 Impact Factor
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    ABSTRACT: Determining the value of livestock breeds is essential to define conservation priorities, manage genetic diversity and allocate funds. Within- and between-breed genetic diversity need to be assessed to preserve the highest intra-specific variability. Information on genetic diversity and risk status is still lacking for many Creole cattle breeds from the Americas, despite their distinct evolutionary trajectories and adaptation to extreme environmental conditions. A comprehensive genetic analysis of 67 Iberoamerican cattle breeds was carried out with 19 FAO-recommended microsatellites to assess conservation priorities. Contributions to global diversity were investigated using alternative methods, with different weights given to the within- and between-breed components of genetic diversity. Information on Iberoamerican plus 15 worldwide cattle breeds was used to investigate the contribution of geographical breed groups to global genetic diversity. Overall, Creole cattle breeds showed a high level of genetic diversity with the highest level found in breeds admixed with zebu cattle, which were clearly differentiated from all other breeds. Within-breed kinships revealed seven highly inbred Creole breeds for which measures are needed to avoid further genetic erosion. However, if contribution to heterozygosity was the only criterion considered, some of these breeds had the lowest priority for conservation decisions. The Weitzman approach prioritized highly differentiated breeds, such as Guabala, Romosinuano, Cr. Patagonico, Siboney and Caracu, while kinship-based methods prioritized mainly zebu-related breeds. With the combined approaches, breed ranking depended on the weights given to the within- and between-breed components of diversity. Overall, the Creole groups of breeds were generally assigned a higher priority for conservation than the European groups of breeds. Conservation priorities differed significantly according to the weight given to within- and between-breed genetic diversity. Thus, when establishing conservation programs, it is necessary to also take into account other features. Creole cattle and local isolated breeds retain a high level of genetic diversity. The development of sustainable breeding and crossbreeding programs for Creole breeds, and the added value resulting from their products should be taken into consideration to ensure their long-term survival.
    Genetics Selection Evolution 09/2013; 45(1):35. DOI:10.1186/1297-9686-45-35 · 3.75 Impact Factor
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    ABSTRACT: Variants in the EDNRB, KIT, MITF, PAX3 and TRPM1 genes are known to cause white spotting phenotypes in horses, which can range from the common white markings up to completely white horses. In this study, we investigated these candidate genes in 169 horses with white spotting phenotypes not explained by the previously described variants. We identified a novel missense variant, PAX3:p.Pro32Arg, in Appaloosa horses with a splashed white phenotype in addition to their leopard complex spotting patterns. We also found three novel variants in the KIT gene. The splice site variant c.1346+1G>A occurred in a Swiss Warmblood horse with a pronounced depigmentation phenotype. The missense variant p.Tyr441Cys was present in several part-bred Arabians with sabino-like depigmentation phenotypes. Finally, we provide evidence suggesting that the common and widely distributed KIT:p.Arg682His variant has a very subtle white-increasing effect, which is much less pronounced than the effect of the other described KIT variants. We termed the new KIT variants W18-W20 to provide a simple and unambiguous nomenclature for future genetic testing applications.
    Animal Genetics 05/2013; 44(6). DOI:10.1111/age.12057 · 2.21 Impact Factor
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    ABSTRACT: Intense selective pressures applied over short evolutionary time have resulted in homogeneity within, but substantial variation among, horse breeds. Utilizing this population structure, 744 individuals from 33 breeds, and a 54,000 SNP genotyping array, breed-specific targets of selection were identified using an F(ST)-based statistic calculated in 500-kb windows across the genome. A 5.5-Mb region of ECA18, in which the myostatin (MSTN) gene was centered, contained the highest signature of selection in both the Paint and Quarter Horse. Gene sequencing and histological analysis of gluteal muscle biopsies showed a promoter variant and intronic SNP of MSTN were each significantly associated with higher Type 2B and lower Type 1 muscle fiber proportions in the Quarter Horse, demonstrating a functional consequence of selection at this locus. Signatures of selection on ECA23 in all gaited breeds in the sample led to the identification of a shared, 186-kb haplotype including two doublesex related mab transcription factor genes (DMRT2 and 3). The recent identification of a DMRT3 mutation within this haplotype, which appears necessary for the ability to perform alternative gaits, provides further evidence for selection at this locus. Finally, putative loci for the determination of size were identified in the draft breeds and the Miniature horse on ECA11, as well as when signatures of selection surrounding candidate genes at other loci were examined. This work provides further evidence of the importance of MSTN in racing breeds, provides strong evidence for selection upon gait and size, and illustrates the potential for population-based techniques to find genomic regions driving important phenotypes in the modern horse.
    PLoS Genetics 01/2013; 9(1):e1003211. DOI:10.1371/journal.pgen.1003211 · 8.17 Impact Factor
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    ABSTRACT: Horses were domesticated from the Eurasian steppes 5,000-6,000 years ago. Since then, the use of horses for transportation, warfare, and agriculture, as well as selection for desired traits and fitness, has resulted in diverse populations distributed across the world, many of which have become or are in the process of becoming formally organized into closed, breeding populations (breeds). This report describes the use of a genome-wide set of autosomal SNPs and 814 horses from 36 breeds to provide the first detailed description of equine breed diversity. F(ST) calculations, parsimony, and distance analysis demonstrated relationships among the breeds that largely reflect geographic origins and known breed histories. Low levels of population divergence were observed between breeds that are relatively early on in the process of breed development, and between those with high levels of within-breed diversity, whether due to large population size, ongoing outcrossing, or large within-breed phenotypic diversity. Populations with low within-breed diversity included those which have experienced population bottlenecks, have been under intense selective pressure, or are closed populations with long breed histories. These results provide new insights into the relationships among and the diversity within breeds of horses. In addition these results will facilitate future genome-wide association studies and investigations into genomic targets of selection.
    PLoS ONE 01/2013; 8(1):e54997. DOI:10.1371/journal.pone.0054997 · 3.53 Impact Factor
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    ABSTRACT: To assist cattle producers transition from microsatellite (MS) to single nucleotide polymorphism (SNP) genotyping for parental verification we previously devised an effective and inexpensive method to impute MS alleles from SNP haplotypes. While the reported method was verified with only a limited data set (N = 479) from Brown Swiss, Guernsey, Holstein, and Jersey cattle, some of the MS-SNP haplotype associations were concordant across these phylogenetically diverse breeds. This implied that some haplotypes predate modern breed formation and remain in strong linkage disequilibrium. To expand the utility of MS allele imputation across breeds, MS and SNP data from more than 8000 animals representing 39 breeds (Bos taurus and B. indicus) were used to predict 9410 SNP haplotypes, incorporating an average of 73 SNPs per haplotype, for which alleles from 12 MS markers could be accurately be imputed. Approximately 25% of the MS-SNP haplotypes were present in multiple breeds (N = 2 to 36 breeds). These shared haplotypes allowed for MS imputation in breeds that were not represented in the reference population with only a small increase in Mendelian inheritance inconsistancies. Our reported reference haplotypes can be used for any cattle breed and the reported methods can be applied to any species to aid the transition from MS to SNP genetic markers. While ~91% of the animals with imputed alleles for 12 MS markers had ≤1 Mendelian inheritance conflicts with their parents' reported MS genotypes, this figure was 96% for our reference animals, indicating potential errors in the reported MS genotypes. The workflow we suggest autocorrects for genotyping errors and rare haplotypes, by MS genotyping animals whose imputed MS alleles fail parentage verification, and then incorporating those animals into the reference dataset.
    Frontiers in Genetics 01/2013; 4:176. DOI:10.3389/fgene.2013.00176
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    ABSTRACT: Source-filter theory provides a framework to interpret the acoustic structure of vertebrate vocalizations in relation to biophysical production, and it predicts that specific acoustic parameters can encode information about callers. Because formant frequencies are determined by vocal tract dimensions, with longer vocal tracts producing lower formants, they can be reliable indicators of body size, as well as other important traits. In polygynous species, reliable acoustic cues to fitness-related traits are expected to be under strong sexual selection pressure through male competition and/or female choice. This study investigates whether formant frequencies of male North American bison bellow vocalizations encode information about fitness-related caller attributes. Bison exhibit male-dominance female-defence polygyny, with dominance displays involving bellows. We hypothesized that physical attributes (mass, age) would predict formants and that formants would in turn predict quality indices (dominance, copulations, offspring sired). Our results showed that heavier bulls produced lower formants and that lower formants predicted higher mating success (copulations), even when controlling for mass. Given positive associations between mating success, dominance and reproductive success (offspring sired) in bison, we conclude that bellows with lower formants reflect greater fitness in bulls. We discuss the importance of reliable acoustic cues to size and quality indices in sexual selection contexts.
    Animal Behaviour 12/2012; 84(6). DOI:10.1016/j.anbehav.2012.08.037 · 3.07 Impact Factor
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    ABSTRACT: American Creole cattle presumably descend from animals imported from the Iberian Peninsula during the period of colonization and settlement, through different migration routes, and may have also suffered the influence of cattle directly imported from Africa. The introduction of European cattle, which began in the 18th century, and later of Zebu from India, has threatened the survival of Creole populations, some of which have nearly disappeared or were admixed with exotic breeds. Assessment of the genetic status of Creole cattle is essential for the establishment of conservation programs of these historical resources. We sampled 27 Creole populations, 39 Iberian, 9 European and 6 Zebu breeds. We used microsatellite markers to assess the origins of Creole cattle, and to investigate the influence of different breeds on their genetic make-up. The major ancestral contributions are from breeds of southern Spain and Portugal, in agreement with the historical ports of departure of ships sailing towards the Western Hemisphere. This Iberian contribution to Creoles may also include some African influence, given the influential role that African cattle have had in the development of Iberian breeds, but the possibility of a direct influence on Creoles of African cattle imported to America can not be discarded. In addition to the Iberian influence, the admixture with other European breeds was minor. The Creoles from tropical areas, especially those from the Caribbean, show clear signs of admixture with Zebu. Nearly five centuries since cattle were first brought to the Americas, Creoles still show a strong and predominant signature of their Iberian ancestors. Creole breeds differ widely from each other, both in genetic structure and influences from other breeds. Efforts are needed to avoid their extinction or further genetic erosion, which would compromise centuries of selective adaptation to a wide range of environmental conditions.
    PLoS ONE 11/2012; 7(11):e49066. DOI:10.1371/journal.pone.0049066 · 3.53 Impact Factor
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    ABSTRACT: Spermatogonial stem cells (SSCs) maintain spermatogenesis throughout a man's life and may have application for treating some cases of male infertility, including those caused by chemotherapy before puberty. We performed autologous and allogeneic SSC transplantations into the testes of 18 adult and 5 prepubertal recipient macaques that were rendered infertile with alkylating chemotherapy. After autologous transplant, the donor genotype from lentivirus-marked SSCs was evident in the ejaculated sperm of 9/12 adult and 3/5 prepubertal recipients after they reached maturity. Allogeneic transplant led to donor-recipient chimerism in sperm from 2/6 adult recipients. Ejaculated sperm from one recipient transplanted with allogeneic donor SSCs were injected into 85 rhesus oocytes via intracytoplasmic sperm injection. Eighty-one oocytes were fertilized, producing embryos ranging from four-cell to blastocyst with donor paternal origin confirmed in 7/81 embryos. This demonstration of functional donor spermatogenesis following SSC transplantation in primates is an important milestone for informed clinical translation.
    Cell stem cell 11/2012; 11(5):715-26. DOI:10.1016/j.stem.2012.07.017 · 22.15 Impact Factor
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    ABSTRACT: Pigtailed macaques (Macaca nemestrina) provide an important model for biomedical research on human disease and for studying the evolution of primate behavior. The genetic structure of captive populations of pigtailed macaques is not as well described as that of captive rhesus (M. mulatta) or cynomolgus (M. fascicularis) macaques. The Washington National Primate Research Center houses the largest captive colony of pigtailed macaques located in several different housing facilities. Based on genotypes of 18 microsatellite (short tandem repeat [STR]) loci, these pigtailed macaques are more genetically diverse than captive rhesus macaques and exhibit relatively low levels of inbreeding. Colony genetic management facilitates the maintenance of genetic variability without compromising production goals of a breeding facility. The periodic introduction of new founders from specific sources to separate housing facilities at different times influenced the colony's genetic structure over time and space markedly but did not alter its genetic diversity significantly. Changes in genetic structure over time were predominantly due to the inclusion of animals from the Yerkes National Primate Research Center in the original colony and after 2005. Strategies to equalize founder representation in the colony have maximized the representation of the founders' genomes in the extant population. Were exchange of animals among the facilities increased, further differentiation could be avoided. The use of highly differentiated animals may confound interpretations of phenotypic differences due to the inflation of the genetic contribution to phenotypic variance of heritable traits. Am. J. Primatol. 74:1017-1027, 2012. © 2012 Wiley Periodicals, Inc.
    American Journal of Primatology 11/2012; 74(11):1017-27. DOI:10.1002/ajp.22055 · 2.14 Impact Factor

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