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PubMed2006

Using genomic inbreeding coefficient estimates for homozygosity mapping of rare recessive traits: application to Taybi-Linder syndrome.

The use of inbred patients whose exact genealogy may not be available is of primary interest in mapping genes involved in rare recessive diseases. We show here that this can be achieved by estimating inbreeding coefficients from the patients' genomic information and using these estimates to perform homozygosity mapping. We show the interest of the approach by mapping a gene for Taybi-Linder syndrome to chromosome 2q, with the use of a key patient with no genealogical information.

Chromosomes, Human, Pair 2↗
PubMed2006

Intrinsic parent-offspring correlation in inbreeding level in a song sparrow (Melospiza melodia) population open to immigration.

The extent to which offspring resemble their parents in genotype and phenotype underpins patterns of genetic and phenotypic variation, selection, and evolution in natural populations. Genetic and phenotypic resemblance can clearly result from additive genetic variance and can be shaped by nongenetic parental and common environmental influences. In contrast, there is no straightforward expectation that inbreeding coefficient (f), a nonadditive component of genetic "quality," should be correlated across parents and offspring in sexually reproducing species or consequently cause resemblance across generations. Here, we report a significant parent f-offspring f correlation within a free-living pedigreed population of song sparrows (Melospiza melodia) on Mandarte Island, Canada. Across 15 years, relatively inbred parents had relatively inbred offspring on average. We show that rather than requiring nonrandom pairing with respect to f and kinship, parent f-offspring f correlations arise as an intrinsic consequence of random pairing within Mandarte's open population, where immigrants interbreed with Mandarte-hatched natives. However, on Mandarte, parent f-offspring f correlations may have been exacerbated because relatively inbred individuals paired with more closely related mates than expected by chance. Such intrinsic parent f-offspring f correlations have major implications for the understanding of resemblance, selection, and evolution in natural populations.

Animal Migration↗
PubMed1984

Additive by additive variance with inbreeding and linkage.

Two-locus coancestries, which provide the coefficients of the additive by additive component in the variance and covariance of relatives for a quantitative trait, were formulated generally in terms of two-locus probabilities of identity by descent for combinations of parental and recombinant gametes. Explicit expressions, with linkage, were developed for all relatives of self-fertilization, for selfed and outbred relatives and for full and half sibs from unrelated inbred parents. The relative effect of linkage on the two-locus coancestry decreases rapidly as inbreeding and relatedness of the relatives increase. It was concluded that the error caused by ignoring linkage would probably be small in the estimation of genetic variances or in the projection of selection response with self-fertilization.

Epistasis, Genetic↗
PubMed1995

The inbreeding effective population number in dioecious populations.

The inbreeding effective population number in a dioecious population with discrete, nonoverlapping generations is investigated for both autosomal and X-linked loci. The recursion relations for the probabilities of genic identity, and the effective population numbers are analyzed and compared in two cases: (i) the offspring identified by sex in the calculation of the probability of common parentage and (ii) the offspring not so identified. Case i gives the correct evolution of the probabilities of identity, but case ii has been more widely studied and applied. A general symmetric framework that reduces the number of parameters is developed and used to examine a wide variety of models of panmixia and monogamy. Cases i and ii agree in many, but not all, models.

Animals↗
PubMed1995

Exact inbreeding coefficient and effective size of finite populations under partial sib mating.

An exact recurrence equation for inbreeding coefficient is derived for a partially sib-mated population of N individuals mated in N/2 pairs. From the equation, a formula for effective size (Ne) taking second order terms of 1/N into consideration is derived. When the family sizes are Poisson or equally distributed, the formula reduces to Ne = [(4 - 3 beta) N/(4 - 2 beta)] + 1 or Ne = [(4 - 3 beta) N/(2 - 2 beta)] - 8/(4 - 3 beta), approximately. For the special case of sib-mating exclusion and Poisson distribution of family size, the formula simplifies to Ne = N + 1, which differs from the previous results derived by many authors by a value of one. Stochastic simulations are run to check our results where disagreements with others are involved.

Animals↗
PubMed1998

Early effect of inbreeding as revealed by microsatellite analyses on Ostrea edulis larvae.

This paper reports new experimental evidence on the effect of inbreeding on growth and survival in the early developmental phase of a marine bivalve, the flat oyster Ostrea edulis. Two crosses between full sibs were analyzed using four microsatellite markers. Samples of 96 individuals were taken just after spawning (day 1), at the end of the larval stage before metamorphosis (day 10) and at the postlarval stage (day 70). Significant departure from Mendelian expectation was observed at two loci in the first cross and two loci in the second. Departure from 1:1 segregation occurred in one parent of the first cross at three loci and genotypic selection, which resulted in highly significant heterozygote excesses, was recorded at three out of four loci in cross C1 and at two out of three loci in cross C2. Across the four markers, there were similar significant excesses of multilocus heterozygosity, and significant multilocus heterozygosity-growth correlations were recorded for both crosses at all stages. These results suggest that microsatellite markers, often assumed to be neutral, cosegregated with fitness-associated genes, the number of which is estimated to be between 15 and 38 in the whole genome, and that there is a potentially high genetic load in Ostrea edulis genome. This load provides a genetic basis for heterosis in marine bivalves.

Animals↗
PubMed2000

A general procedure for predicting rates of inbreeding in populations undergoing mass selection.

Predictions of rates of inbreeding (DeltaF), based on the concept of long-term genetic contributions assuming the infinitesimal model, are developed for populations with discrete or overlapping generations undergoing mass selection. Phenotypes of individuals are assumed to be recorded prior to reproductive age and to remain constant over time. The prediction method accounts for inheritance of selective advantage both within and between age classes and for changing selection intensities with age. Terms corresponding to previous methods that assume constant selection intensity with age are identified. Predictions are accurate (relative errors < or =8%), except for cases with extreme selection intensities in females in combination with high heritability. With overlapping generations DeltaF reaches a maximum when parents are equally distributed over age classes, which is mainly due to selection of the same individuals in consecutive years. DeltaF/year decreases much more slowly compared to DeltaF/generation as the number of younger individuals increases, whereas the decrease is more similar as the number of older individuals increases. The minimum DeltaF (per year or per generation) is obtained when most parents were in the later age classes, which is mainly due to an increased number of parents per generation. With overlapping generations, the relationship between heritability and DeltaF is dependent on the age structure of the population.

Inbreeding↗
PubMed2001

Quantitative trait locus analysis in crosses between outbred lines with dominance and inbreeding.

We provide a theoretical framework for quantitative trait locus (QTL) analysis of a crossed population where parental lines may be outbred and dominance as well as inbreeding are allowed for. It can be applied to any pedigree. A biallelic QTL is assumed, and the QTL allele frequencies can be different in each breed. The genetic covariance between any two individuals is expressed as a nonlinear function of the probability of up to 15 possible identity modes and of the additive and dominance effects, together with the allelic frequencies in each of the two parental breeds. The probabilities of each identity mode are obtained at the desired genome positions using a Monte Carlo Markov chain method. Unbiased estimates of the actual genetic parameters are recovered in a simulated F(2) cross and in a six-generation complex pedigree under a variety of genetic models (allele fixed or segregating in the parental populations and additive or dominance action). Results from analyzing an F(2) cross between Meishan and Large White pigs are also presented.

Alleles↗
PubMed2001

Heterosis, marker mutational processes and population inbreeding history.

Genotype-fitness correlations (GFC) have previously been studied using allozyme markers and have often focused on short-term processes such as recent inbreeding. Thus, models of GFC usually neglect marker mutation and only use heterozygosity as a genotypic index. Recently, GFC have also been reported (i) with DNA markers such as microsatellites, characterized by high mutation rates and specific mutational processes and (ii) using new individual genotypic indices assumed to be more precise than heterozygosity. The aim of this article is to evaluate the theoretical impact of marker mutation on GFC. We model GFC due to short-term processes generated by the current breeding system (partial selfing) and to long-term processes generated by past population history (hybridization). Various mutation rates and mutation models corresponding to different kinds of molecular markers are considered. Heterozygosity is compared to other genotypic indices designed for specific marker types. Highly mutable markers (such as microsatellites) are particularly suitable for the detection of GFC that evolve in relation to short-term processes, whereas GFC due to long-term processes are best observed with intermediate mutation rates. Irrespective of the marker type and population scenario, heterozygosity usually provides higher correlations than other genotypic indices under most biologically plausible conditions.

Alleles↗
PubMed2002

Selection, load and inbreeding depression in a large metapopulation.

The subdivision of a species into local populations causes its response to selection to change, even if selection is uniform across space. Population structure increases the frequency of homozygotes and therefore makes selection on homozygous effects more effective. However, population subdivision can increase the probability of competition among relatives, which may reduce the efficacy of selection. As a result, the response to selection can be either increased or decreased in a subdivided population relative to an undivided one, depending on the dominance coefficient F(ST) and whether selection is hard or soft. Realistic levels of population structure tend to reduce the mean frequency of deleterious alleles. The mutation load tends to be decreased in a subdivided population for recessive alleles, as does the expected inbreeding depression. The magnitude of the effects of population subdivision tends to be greatest in species with hard selection rather than soft selection. Population structure can play an important role in determining the mean fitness of populations at equilibrium between mutation and selection.

Animals↗
PubMed2003

Maximum-likelihood and markov chain monte carlo approaches to estimate inbreeding and effective size from allele frequency changes.

Maximum-likelihood and Bayesian (MCMC algorithm) estimates of the increase of the Wright-Malécot inbreeding coefficient, F(t), between two temporally spaced samples, were developed from the Dirichlet approximation of allelic frequency distribution (model MD) and from the admixture of the Dirichlet approximation and the probabilities of fixation and loss of alleles (model MDL). Their accuracy was tested using computer simulations in which F(t) = 10% or less. The maximum-likelihood method based on the model MDL was found to be the best estimate of F(t) provided that initial frequencies are known exactly. When founder frequencies are estimated from a limited set of founder animals, only the estimates based on the model MD can be used for the moment. In this case no method was found to be the best in all situations investigated. The likelihood and Bayesian approaches give better results than the classical F-statistics when markers exhibiting a low polymorphism (such as the SNP markers) are used. Concerning the estimations of the effective population size all the new estimates presented here were found to be better than the F-statistics classically used.

Gene Frequency↗
PubMedDate not supplied

The inbreeding effective population number and the expected homozygosity for an X-linked locus.

Assuming random mating and discrete nonoverlapping generations, the inbreeding effective population number, N(i)e, is calculated for an X-linked locus. For large populations, the result agrees with the variance effective population number. As an application, the maintenance of genetic variability by the joint action of mutation and random drift is investigated. It is shown that, if every allele mutates at rate u to new types, then the probabilities of identify in state (and hence the expected homozygosity of females) converge to the approximate value (1 + 4N(i)eu)-1 at the approximate asymptotic rate exp(-[2u + (2N(i)e)-1]t).

Animals↗
PubMedDate not supplied

Inbreeding, mortality, and sex ratio in gaur (Bos gaurus) under captivity.

The average inbreeding coefficient for gaur (Bos gaurus H. Smith) born in captivity has ranged from 0.139 to 0.234 per year since 1969. Juvenile mortality is significantly higher among inbred young, and a significantly higher proportion of males occur in inbred than in noninbred offspring.

Animals↗
PubMedDate not supplied

Inbreeding, coancestry, and covariance between relatives for X-chromosomal loci.

Knowledge about the relationships between relatives for X-chromosomal loci is necessary to compute genetic variances and covariances for the genetic evaluation of individuals for economically important traits in livestock and poultry. Using a unified approach, we derived explicitly the coefficient of inbreeding for individuals and the coefficient of coancestry between collateral and lineal relatives of the same or different sex, assuming that the male is heterogametic and the female is homogametic. Collateral relatives include full sibs, paternal and maternal half-sibs, paternal and maternal single first cousins, and double first cousins. Lineal relatives include parent-offspring, paternal and maternal grandparent-grandoffspring, and aunt- or uncle-niece or -nephew. We also defined additive and dominance relationships to compute genetic covariance between relatives, assuming random mating equilibrium, and clarified misinterpretations and corrected errors in the literature. Our results are also applicable to organisms that have few autosomal loci, such as Drosophila, in which X-chromosomal loci can account for a large amount of genetic variance, and to haplodiploid organisms, such as the honeybee, in which the entire genome is equivalent to being X-chromosomal.

Animals↗
PubMed2005

Spawning, copulation and inbreeding coefficients in marine invertebrates.

Patterns of population genetic variation have frequently been understood as consequences of life history covariates such as dispersal ability and breeding systems (e.g. selfing). For example, marine invertebrates show enormous variation in life history traits that are correlated with the extent of gene flow between populations and the magnitude of differentiation among populations at neutral genetic markers (FST). Here we document an unexpected correlation between marine invertebrate life histories and deviation from Hardy-Weinberg equilibrium (non-zero values of FIS, the inbreeding coefficient). FIS values were significantly higher in studies of species with free-spawned planktonic sperm than in studies of species that copulate or have some form of direct sperm transfer to females or benthic egg masses. This result was robust to several different analytical approaches. We note several mechanisms that might contribute to this pattern, and appeal for more studies and ideas that might help to explain our observations.

Animals↗
PubMed2000

The consequences of inbreeding for recognizing competitors.

Extreme inbreeding will compromise an animal's ability to discriminate between individuals and, thus, assess familiarity and kinship with conspecifics. In rodents, a large component of individual recognition is mediated through chemical communication. The counter-marking of competitor males' scent marks provides a measure of discrimination between their own scent and that from other individuals. We investigated whether males in common outbred (ICR(CD-1) and TO) and inbred (BALB/c) strains of laboratory mice could recognize the urinary scents of other individuals by measuring their investigation and counter-marking responses. Dominant males of outbred strains investigated and counter-marked scents from other males, whether of the same or another strain. Dominant inbred BALB/c males investigated but did not counter-mark their own strain scents, counter-marking only those from another strain. They did not use environmentally induced status differences in odours to recognize scents from other males. The inability of the inbred mice to discriminate between their own scent marks and those of other males is likely to alter their competitive behaviour, which could influence responses in experiments and the welfare of caged laboratory mice.

Aggression↗
PubMed2004

Molecular evidence of post-copulatory inbreeding avoidance in the field cricket Gryllus bimaculatus.

Female promiscuity has broad implications for individual behaviour, population genetics and even speciation. In the field cricket Gryllus bimaculatus, females will mate with almost any male presented to them, despite receiving no recorded direct benefits. Previous studies have shown that female crickets can benefit from polyandry through increased hatching success of their eggs. There is evidence that this effect is driven by the potential of polyandrous females to avoid fertilizing eggs with sperm from genetically incompatible males. We provide direct evidence supporting the hypothesis that polyandry is a mechanism to avoid genetic incompatibilities resulting from inbreeding. Using microsatellite markers we examined patterns of paternity in an experiment where each female mated with both a related and an unrelated male in either order. Overall, unrelated males were more successful in gaining paternity than were related males, but this effect was driven by a much greater success of unrelated males when they were the first to mate.

Animals↗
PubMed2005

Hamilton and Zuk meet heterozygosity? Song repertoire size indicates inbreeding and immunity in song sparrows (Melospiza melodia).

Hamilton and Zuk's influential hypothesis of parasite-mediated sexual selection proposes that exaggerated secondary sexual ornaments indicate a male's addictive genetic immunity to parasites. However, genetic correlated of ornaments and immunity have rarely been explicitly identified. Evidence supporting Hamilton and Zuk's hypothesis has instead been gathered by looking for positive phenotypic correlations between ornamentation and immunity; such correlations are assumed to reflect causal, addictive relationships between these traits. We show that in a song sparrows, Melospiza melodia, male's song repertoire size, a secondary sexual trait, increased with his cell-mediated immune response (CMI) to an experimental challenge. However, this phenotypic correlation could be explained because both repertoire size and CMI declined with a male's inbreeding level. Repertoire size therefore primarily indicated a male's relative heterozygosity, a non-addictive genetic predictor of immunity. Caution may therefore be required when interpreting phenotypic correlations as support for Hamilton and Zuk's addictive model of sexual selection. However, our results suggest that female song sparrows choosing with large repertoires would on average acquire more outbred and therefore more heterozygous mates. Such genetic dominance effects on ornamentation are likely to influence evolutionary trajectories of female choice, and should be explicitly incorporated into genetic models of sexual selection.

Animals↗