The genetic dissection of complex traits in a founder population

We estimated broad heritabilities (H(2)) and narrow heritabilities (h(2)) and conducted genomewide screens, using a novel association-based mapping approach for 20 quantitative trait loci (QTLs) among the Hutterites, a founder population that practices a communal lifestyle. Heritability estimates ranged from.21 for diastolic blood pressure (DBP) to.99 for whole-blood serotonin levels. Using a multipoint method to detect association under a recessive model we found evidence of major QTLs for six traits: low-density lipoprotein (LDL), triglycerides, lipoprotein (a) (Lp[a]), systolic blood pressure (SBP), serum cortisol, and whole-blood serotonin. Second major QTLs for Lp(a) and for cortisol were identified using a single-point method to detect association under a general two-allele model. The heritabilities for these six traits ranged from.37 for triglycerides to.99 for serotonin, and three traits (LDL, SBP, and serotonin) had significant dominance variances (i.e., H(2) > h(2)). Surprisingly, there was little correlation between measures of heritability and the strength of association on a genomewide screen (P>.50), suggesting that heritability estimates per se do not identify phenotypes that are influenced by genes with major effects. The present study demonstrates the feasibility of genomewide association studies for QTL mapping. However, even in this young founder population that has extensive linkage disequilibrium, map densities <5 cM may be required to detect all major QTLs.     

SASQuant: a SAS software program to estimate genetic effects and heritabilities of quantitative traits in populations consisting of 6 related generations

Plant breeders are interested in the analysis of phenotypic data to measure genetic effects and heritability of quantitative traits and predict gain from selection. Measurement of phenotypic values of 6 related generations (parents, F(1), F(2), and backcrosses) allows for the simultaneous analysis of both Mendelian and quantitative traits. In 1997, Liu et al. released a SAS software based program (SASGENE) for the analysis of inheritance and linkage of qualitative traits. We have developed a new program (SASQuant) that estimates gene effects (Hayman's model), genetic variances, heritability, predicted gain from selection (Wright's and Warner's models), and number of effective factors (Wright's, Mather's, and Lande's models). SASQuant makes use of traditional genetic models and allows for their easy application to complex data sets. SASQuant is freely available and is intended for scientists studying quantitative traits in plant populations.     

The beta-binomial model for estimating heritabilities of binary traits

Calculations of individual narrow-sense heritability and family mean heritability of a binary trait in stochastically simulated sib trials in completely randomized block experiments showed that in some situations estimates of realized heritabilities obtained from the mixed linear threshold model could be improved by application of a proposed beta-binomial model. The proposed model adopts the beta-binomial as the conjugate-prior for the distribution of probabilities of observing the binary trait in a genetic entry. Estimation of the beta parameters allows an estimation of selection response and, by linkage to a threshold model for the individual observations, the desired heritabilities can be obtained. The average bias in the betabinomial estimates of heritability and family mean heritability was less than 2%. Improvements over existing procedures were especially manifest at heritabilities above 0.3 and at low overall probabilities of observing the trait (p < 0.30). The lowest root mean square errors were consistently obtained with the algorithm proposed by Harville and Mee (1984). The beta-binomial framework, although restricted to a single random additive genetic effect, further facilitates general analysis, estimation of selection response, and calculation of reliable family mean heritability. Intraclass correlations can be estimated directly from the beta-binomial parameters.     

Mapping quantitative trait Loci underlying fitness-related traits in a free-living sheep population

We searched for quantitative trait loci (QTL) underlying fitness-related traits in a free-living pedigree of 588 Soay sheep in which a genetic map using 251 markers with an average spacing of 15 cM had been established previously. Traits examined included birth date and weight, considered both as maternal and offspring traits, foreleg length, hindleg length, and body weight measured on animals in August and jaw length and metacarpal length measured on cleaned skeletal material. In some cases the data were split to consider different age classes separately, yielding a total of 15 traits studied. Genetic and environmental components of phenotypic variance were estimated for each trait and, for those traits showing nonzero heritability (N= 12), a QTL search was conducted by comparing a polygenic model with a model including a putative QTL. Support for a QTL at genome-wide significance was found on chromosome 11 for jaw length; suggestive QTL were found on chromosomes 2 and 5 (for birth date as a trait of the lamb), 8 (birth weight as a trait of the lamb), and 15 (adult hindleg length). We discuss the prospects for refining estimates of QTL position and effect size in the study population, and for QTL searches in free-living pedigrees in general.     

The phenotypic distribution of quantitative traits in a wild mouse F1 population

The human complex diseases such as hypertension, precocious puberty, and diabetes have their own diagnostic thresholds, which are usually estimated from the epidemiological data of nature populations. In the mouse models, numerous phenotypic data of complex traits have been accumulated; however, knowledge of the phenotypic distribution of the natural mouse populations remains quite limited. In order to investigate the distribution of quantitative traits of wild mice, 170 F1 progeny aged 8-10?weeks and derived from wild mice collected from eight spots in the suburbs of Shanghai were tested for their values of anatomic, blood chemical, and blood hematological parameters. All the wild mice breeders were of Mus. m. musculus and Mus. m. castaneus maternal origin according to the single nucleotide polymorphism (SNP) markers of the mitochondrial DNA. The results showed that phenotypes in wild mice had a normal distribution with four to six times the standard deviation. For the majority of the traits, the wild outbred mice and laboratory inbred mice have significantly different ranges and mean values, whereas the wild mice did not necessarily show more phenotypic diversity than the inbred ones. Our data also showed that natural populations may have some unique phenotypes related to sugar and protein metabolism, as the mean value of wild mice differ dramatically from the inbred mice in the levels of blood glucose, BUN (blood urea nitrogen), and total blood protein. The epidemiological information of the complex traits in the nature population from our study provided valuable reference for the application of mouse models in those complex disease studies.     

Maximum-likelihood variance components analysis of heritabilities of cranial nonmetric traits

Nonmetric traits of the cranium are often used to support hypotheses of the history and divergence of human populations. These studies rely on the assumption that nonmetric traits are heritable, yet few skeletal series exist with associated pedigree information that allow for the calculation of additive genetic variance, or heritability. In addition, traits for which heritabilities have been published represent dichotomous present/absent forms instead of the range of expression that can be observed for many nonmetric characters. In the present study I use a maximum-likelihood variance components analysis to calculate univariate narrow-sense heritability estimates on the skeletal series from Hallstatt, Austria, for 9 sutural bones, 27 multilevel traits, and dichotomized present/absent forms for 19 of these multilevel characters. Most of the trait heritabilities do not differ significantly from a model of h2 = 0, and they have large standard errors. In a heuristic comparison of multilevel versus dichotomous trait forms, most of the nonmetric characters showed no differences in heritability between the two methods used for parsing the phenotypic variation, although where differences were noted, the presence-absence version had higher heritabilities. These results have implications not only for the use of particular nonmetric traits in population studies but also for the practice of character dichotomization in data collection.     

Associations between quantitative traits and enzyme loci in the F2 population of a maize hybrid

Summary Univariate and multivariate analyses were used to identify associations between eight enzyme marker loci and 11 quantitative traits of maize (Zea mays L.). The material analyzed included inbred lines Wf9 and Pa405, single-cross hybrid Wf9 X Pa405, and the F2 generation of the selfed single-cross hybrid. Each enzyme locus assayed was associated with at least one quantitative trait, and all quantitative traits were associated with genotypes at particular enzyme loci. Significant associations also were found between the level of heterozygosity per individual and nine of 11 quantitative traits. The total contribution to heterosis, for seed yield per plant, of genes linked with the eight enzyme loci, was 27% of the F2 mean and 18% of the difference in mean between the F1 hybrid and the inbred parents. Genes linked with Glu1 accounted for nearly one third of the total dominance effect detected by the eight enzyme loci. The chromosome segments marked by loci with significant effects on seed yield were markedly overdominant. The large heterotic effects of chromosome segments marked by particular loci suggest that enzyme loci could be used to help transfer genes responsible for heterosis to inbred lines. We conclude that analyses of additional inbred lines, F1 hybrids, and F2 populations in more environments will halp identify specific associations between enzyme loci, or chromosome segments which they mark, and important agronomic traits.Cooperative investigations of the USDA, ARS and Dept. of Plant Sciences, South Dakota State Univ. (SDSU), Brookings, Journal Series No. 2039; and the Institute of Animal Resource Ecology, Univ. of British Columbia, Vancouver, B.C. V6T 1W5, Canada     

The effective founder effect in a spatially expanding population

The gradual loss of diversity and the establishment of clines in allele frequencies associated with range expansions are patterns observed in many species, including humans. These patterns can result from a series of founder events occurring as populations colonize previously unoccupied areas. We develop a model of an expanding population and, using a branching process approximation, show that spatial gradients reflect different amounts of genetic drift experienced by different subpopulations. We then use this model to measure the net average strength of the founder effect, and we demonstrate that the predictions from the branching process model fit simulation results well. We further show that estimates of the effective founder size are robust to potential confounding factors such as migration between subpopulations. We apply our method to data from Arabidopsis thaliana. We find that the average founder effect is approximately three times larger in the Americas than in Europe, possibly indicating that a more recent, rapid expansion occurred.     

On the survival of a gene represented in a founder population

Gene survival in a population which increases without density dependence is considered using a generalization of the Moran model for haploid individuals. It is shown that situations where ultimate homozygosity is certain and where there is a non-zero probability of balanced polymorphism are both possible. Necessary and sufficient conditions in terms of the mean of the population growth distribution are given which determine which of these situations holds.     

The use of quantitative traits in the study of human population structure

Studies of human population structure and history have tended to use demographic and/or serological data for analysis. This paper reviews the methods and studies that incorporate quantitative traits (usually polygenic traits) in such analyses. Methods of assessing the degree and pattern of among-group variation are discussed, and are characterized as being model-free or model-bound. Model-free methods deal with the measure of overall populational differentiation and with comparative methods for describing the pattern of differentiation. Model-bound methods are used for direct incorporation into theoretical models of population structure in order to estimate genetic parameters, such as those in admixture and isolation by distance models. To date, studies have indicated that quantitative traits may often be used successfully in studies of human population structure, and show effects of microevolutionary forces on quantitative variation among populations.     

Genetic parameters in a rubber tree population: heritabilities,genotype-by-environment interactions and multi-trait correlations

Rubber tree breeding programs are mainly driven by selection of individuals with high yield and quality of rubber. Data from 51 open-pollinated progenies tested on six sites in Brazil were analyzed over several traits to estimate the following: genetic parameters such as narrow-sense heritability and additive genetic variance in single- and multi-site analyses, type B correlations to determine the relevance of genotype-by-environment interactions and its effects on alternative selection strategies, additive genetic repeatability correlation for rubber yield based on three consecutive yearly measurements, and type A correlations to evaluate trait-to-trait genetic associations for all measured traits. Average rubber yield (RYm) showed an estimated narrow-sense heritability of 0.31, with an estimated type B correlation of 0.84, indicating low levels of genotype-by-environment interaction. The trait survival and number of latex vessel rings (RG) showed larger genotype-by-environment interaction and the lowest heritabilites. High to moderate type B correlation was found for most traits, with a value of 0.85 between diameter (or girth) and RYm; therefore, it is possible to achieve interesting rubber yield genetic gains (over 3 years of measurements) from indirect selection based on diameter at age 2.     

Re-creation of the genetic composition of a founder population

Human ethnic groups are frequently comprised of two or more founder populations. One of these founding populations is often available for contemporary sampling. We describe a method for reconstructing the composition of a missing founder population using the highly informative haplotypes comprising the HLA system. An application of the method is demonstrated using bone marrow registry samples of African Americans. We use contemporary samples of African Americans and European Americans to derive haplotypes of the West African founder populations. This approach may also be useful for reconstructing ancestral haplotypes for regions elsewhere in the genome.     

Effects of various breeding strategies on diploid drone frequency and quantitative traits in a honey bee population

When selecting in a finite population of honeybees there is a conflict between gain in a quantitative trait and increasing homozygosity, and therefore the frequency of inviable diploid drones. The consequences when using different mating, import, and selection strategies on diploid drone frequency and genetic gain, was explored with Monte Carlo computer simulations.Within a closed population breeding structure, mass selection gave the highest genetic gain in the quantitative trait, but also the largest increase in percentage diploid drones and queens with unacceptably-low brood viability. Mass selection combined with truncation selection against queens having more than 15% diploid drones gave a comparable genetic gain and was the best strategy of the ones studied to avoid diploid drones. Within-family selection (one replacement per sib group) gave the least genetic gain, and a frequency of diploid drones comparable to random (no) selection. It was intermediate between mass selection and mass selection combined with viability selection concerning the frequency of diploid drones.Insemination with pooled and homogenized semen originating from all breeder queens (30), as compared to natural mating with 12 randomly-selected drones, had little effect on the genetic gain and on the overall frequency of diploid drones (10 to 15% by generation 20).The effect of opening the closed breeding population for the import of external queens every generation, by exchanging breeder queens of lowest performance with a corresponding number of new queens (5, 10and 15 out of 30), was also investigated. Under mass selection (natural mating as well as artificial insemination) the frequency of diploid drones and the proportion of queens discarded were reduced because of low brood viability. However, artificial insemination was superior to natural mating considering the latter criterion. If the imported queens were at the same genetic level for the quantitative trait under selection as the whole breeding population at that generation, or 10% better, the genetic gain was respectively slightly reduced and approximately maintained. If the imported queens were of inferior quality (equal to the initial population) the import of queens slowed genetic progress considerably.     

广义与狭义植物内生生物的定义及其研究进展

本文从比较植物内生生物的概念入手,提出了广义与狭义两种植物内生生物的定义;归纳了植物内生生物的物种多样性、分布、及其代谢特点;分析了植物内生生物与寄主植物的关系;探讨了部分植物内生生物潜在的价值和应用前景。     

A population genetics model for multiple quantitative traits exhibiting pleiotropy and epistasis

We study a population genetics model of an organism with a genome of L(tot)loci that determine the values of T quantitative traits. Each trait is controlled by a subset of L loci assigned randomly from the genome. There is an optimum value for each trait, and stabilizing selection acts on the phenotype as a whole to maintain actual trait values close to their optima. The model contains pleiotropic effects (loci can affect more than one trait) and epistasis in fitness. We use adaptive walk simulations to find high-fitness genotypes and to study the way these genotypes are distributed in sequence space. We then simulate the evolution of haploid and diploid populations on these fitness landscapes and show that the genotypes of populations are able to drift through sequence space despite stabilizing selection on the phenotype. We study the way the rate of drift and the extent of the accessible region of sequence space is affected by mutation rate, selection strength, population size, recombination rate, and the parameters L and T that control the landscape shape. There are three regimes of the model. If LTL(tot), there are many small peaks that can be spread over a wide region of sequence space. Compensatory neutral mutations are important in the population dynamics in this case.     

Sexually dimorphic inflorescence traits in a wind-pollinated species: heritabilities and genetic correlations in Schiedea adamantis (Caryophyllaceae)

Sexual dimorphism may be especially pronounced in wind-pollinated species because they lack the constraints of biotically pollinated species that must present their pollen and stigmas in similar positions to ensure pollen transfer. Lacking these constraints, the sexes of wind-pollinated species may diverge in response to the different demands of pollen dispersal and receipt, depending on the magnitude of genetic correlations preventing divergence between sexes. Patterns of sexual dimorphism and genetic variation were investigated for inflorescence traits in Schiedea adamantis (Caryophyllaceae), a species well adapted to wind-pollination, and compared to S. salicaria, a species with fewer adaptations to wind pollination. For S. adamantis, dimorphism was pronounced for inflorescence condensation and its components, including lateral flower number and pedicel length. Within sexes, genetic correlations between traits may constrain the relative shape of the inflorescence. Correlations detected across sexes may retard the evolution of sexual dimorphism in inflorescence structure, including features favoring enhanced dispersal and receipt of pollen. Despite genetic correlations across sexes, common principal components analysis showed that genetic variance-covariance matrices (G matrices) differed significantly between the sexes, in part because of greater genetic variation for flower number in hermaphrodites than in females. G matrices also differed between closely related S. adamantis and S. salicaria, indicating the potential for divergent evolution of inflorescence structure despite general similarities in morphology and pollination biology.     

Molecular mapping of quantitative trait loci for three kernel-related traits in maize using a double haploid population

Kernel size and kernel weight are important factors possibly involved in the determination of grain yield in maize, so identifying the genetic basis of kernel-related traits provides insights into the breeding of high-yield maize varieties. Kernel length (KL), kernel width (KW) and hundred kernel weight (HKW) were evaluated in three various planting conditions for the 240 field-grown double haploid (DH) lines derived from the single-cross hybrid Xianyu335. Variations in KL, KW and HKW were observed among DH lines, and all three traits showed a broad sense heritability of 76%. A total of 964 single nucleotide polymorphisms (SNPs) from the MaizeSNP3072 chip was utilised to create a high-density genetic map of 1546.4 cM and to identify quantitative trait loci (QTLs). Using composite interval mapping, a total of five, seven and five QTLs have been mapped for KL, KW and HKW, respectively. qkl1-2 and qkl4-1 explained 17.8% and 14.2% of the phenotypic variation in KL, respectively, and the other three QTLs contributed 3.2–4.0%. The phenotypic variation explained (PVE) of seven QTLs responsible for KW ranged from 3.3 to 9.5%. Three QTLs for HKW, qhkw1, qhkw5 and qhkw10 each explained more than 10% of the phenotypic variation, and qhkw4 and qhkw9 accounted for 3.0% and 6.0%, respectively. Due to their detection in multiple planting environments, the loci mapped here appear to be potential targets for the improvement of maize grain yield.     

Mapping of quantitative trait loci for carcass traits in a Japanese Black (Wagyu) cattle population

To detect quantitative trait loci (QTL) that influence economically important traits in a purebred Japanese Black cattle population, we performed a preliminary genome-wide scan using 187 microsatellite markers across a paternal half-sib family composed of 258 offspring. We located six QTL at the 1% chromosome-wise level on bovine chromosomes (BTA) 4, 6, 13, 14 and 21. A second screen of these six QTL regions using 138 additional paternal offspring half-sib from the same sire, provided further support for five QTL: carcass weight on BTA14 (22-39 cM), one for rib thickness on BTA6 (27-58 cM) and three for beef marbling score (BMS) on BTA4 (59-67 cM), BTA6 (68-89 cM) and BTA21 (75-84 cM). The location of QTL for subcutaneous fat thickness on BTA13 was not supported by the second screen (P > 0.05). We determined that the combined contribution of the three QTLs for BMS was 10.1% of the total variance. The combined phenotypic average of these three Q was significantly different (P < 0.001) from those of other allele combinations. Analysis of additional half-sib families will be necessary to confirm these QTL.