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Comparison of selection methods at the same level of inbreeding.

Animal geneticists predict higher genetic responses to selection by increasing the accuracy of selection using BLUP with information on relatives. Comparison of different selection methods is usually made with the same total number tested and with the same number of parents and mating structure so as to give some acceptable (low) level of inbreeding. Use of family information by BLUP results in the individuals selected being more closely related, and the levels of inbreeding are increased, thereby breaking the original restriction on inbreeding. An alternative is to compare methods at the same level of inbreeding. This would allow more intense selection (fewer males selected) with the less accurate methods. Stochastic simulation shows that, at the same level of inbreeding, differences between the methods are much smaller than if inbreeding is unrestricted. If low to moderate inbreeding levels are targeted, as in a closed line of limited size, then selection on phenotype can yield higher genetic responses than selection on BLUP. Extra responses by BLUP are at the expense of extra inbreeding. The results derived here show that selection on BLUP of breeding values may not be optimal in all cases. Thus, current theory and teaching on selection methods are queried. Revision of the methodology and a reappraisal of the optimization results of selection theory are required.

Animals↗

Growth patterns of Angus, Hereford and shorthorn cattle. I. Comparison of inbred and noninbred lines, changes in patterns over time and effects of level of inbreeding and reproductive performance.

Mature weight (A) and rate of maturing (K) were estimated for 283 Angus, 140 Hereford and 280 Shorthorn cows utilizing the asymptotic regression equation Yt=A(1-Be-Kt). The Yt was weight of the individual at age t; and B was an estimate related to early life weight changes and provided for a Y-intercept (A-B). Each breed consisted of four inbred and two noninbred lines. Regression of estimated growth curve parameters on levels of inbreeding of the individuals and of their dams and effects of early reproductive performance (EREPRO) were studied as sources of variation in addition to line differences and trends in line values over years. Considered jointly with inbreeding of the dam and with EREPRO, inbreeding of the individual was negatively related (P less than .01) to estimates of A in the three breeds and unrelated (P greater than .10) to estimates of K. Each 1% increase in inbreeding of the individual was associated with about 2 kg decrease in estimated mature weight. An increase in inbreeding of the dam of an individual was negatively related to estimates of K in Angus (P less than .01) and Shorthorns (P less than .05). Inbreeding of dams was positively related to estimates of A in the three breeds, but only in Shorthorns could the relationship be declared significant. Estimates of A were about 46 kg heavier and estimates of K about .010 less for each year an individual failed to produce a calf during her first three opportunities. In general, A values declined in all three breeds during the study. Significant changes were observed in all Hereford analyses and after inbreeding was included in the Angus analysis, while inclusion of inbreeding in the Shorthorn analysis caused the change to become unimportant. The K values increased in all three breeds during the study; however, the change could be declared significant only in Herefords.

Analysis of Variance↗

Linear and curvilinear effects of inbreeding on production traits for walloon Holstein cows.

The nonlinear effects of inbreeding were studied by comparing linear and curvilinear regression models of phenotypic performances on inbreeding coefficients for production traits (milk, fat, and protein yields) of Holstein cows in their first lactation. Three different regression models (linear, quadratic, and cubic) were introduced separately into a single-trait, single-lactation, random regression test-day model. The significance of the different regression coefficients was studied based on a t-test after estimation of error variances and covariances associated with the different regression coefficients. All of the tested regression coefficients were significantly different from 0. The traditional regression coefficients of milk, fat, and protein yields on inbreeding were, respectively, -22.10, -1.10, and -0.72 kg for Holstein cows in their first lactation. However, the estimates of 305-d production losses for various classes of animals based on inbreeding coefficients showed that the effect of inbreeding was not a linear function of the percentage of inbreeding. The 305-d milk yield loss profiles attributable to inbreeding, obtained by the various regression models, were different. However, for inbreeding coefficients between 0 and 10%, these differences were small.

Animals↗

Inbreeding and the gene pool.

The trend in the artificial insemination industry in recent years has been to sample larger numbers of sons sired by the most popular bulls. This trend has caused concern in the dairy industry regarding inbreeding and the gene pool. The known detrimental effects of inbreeding on economically important traits are one reason for this concern, and these are reviewed here. Also reviewed and discussed are estimates of inbreeding in dairy cattle populations. These estimates indicate that for the populations studied, inbreeding has increased little if at all during the period of widespread use of artificial insemination. During the 1970's average inbreeding in United States Holsteins and British Friesians was on the order of 3 to 6% relative to their foundations. A recent study of inbreeding in United States Ayrshires suggests little inbreeding in that breed in spite of the relatively small population size. Inbreeding and preservation of genetic variation should be minor concerns in selecting sires.

Animals↗

Estimates of inbreeding and relationship among registered Holstein females in the United States.

The estimate of inbreeding for registered Holstein females born during 1990 was 5.1 +/- 0.4% for a random sample of 600 two-line pedigrees. Previously published estimates were 4.7% for 1970, 3.8% for 1976, and 4.3% for 1982 from similar samples of pedigrees. These estimates were calculated using a base of approximately 1884, or the initiation of herd-book registration in the US. The estimate of relationship between randomly paired females born during 1990 was 10.2 +/- 0.8%; relationships were 5.2% for 1970, 7.3% for 1976, and 9.8% for 1982. Average relationship within the breed increased significantly without a corresponding increase in inbreeding. Inbreeding was also estimated for alternative base years with 10-yr increments to determine the effect of base year on estimates of inbreeding. Using 1950 as the base year, inbreeding was estimated at 0.5% for 1970, 0.3% for 1976, 1.6% for 1982, and 2.1% for 1990. Estimates using 1920 as the base year were 2.0% for 1970, 1.9% for 1976, 2.3% for 1982, and 3.2% for 1990. More recent base years gave lower estimates of inbreeding, as expected, but showed an exaggerated percentage of increase in inbreeding from 1970 to 1990. However, the annual amount of increase of inbreeding from 1976 to 1990 was not significantly affected by time of base year and ranged from 0.08 to 0.12/yr. The five most influential bulls of the breed were Pawnee Farm Arlinda Chief 1427381, Round Oak Rag Apple Elevation 1491007, S-W-D Valiant 1650414, Osborndale Ivanhoe 1189870, and Sir Pietertje Ormsby Mercedes 44931; estimated direct relationships to the breed were 0.123, 0.122, 0.096, 0.083, and 0.074, respectively.

Animals↗

When not to avoid inbreeding.

Avoidance of incestuous matings is widely reported across many animal taxa, and the adaptive value of such behavior is explained through inbreeding depression. However, an old and somewhat neglected theoretical result predicts that inbred matings offer another, positive effect on the inclusive fitness of parents: an individual who mates with a relative will help that relative to spread genes identical by descent. This benefit can be substantial, if the additional mating achieved by the relative does not harm his mating success otherwise, and in the context of selfing in plants the phenomenon is well known. Here, we develop a model that derives expected values of inbreeding tolerance, that is, the magnitude of inbreeding depression that is required to make individuals avoid inbreeding, for different animal life histories and parental investment patterns. We also distinguish between simultaneous and sequential mate choice, and show that inbreeding tolerance should often be remarkably high in the latter scenario in particular, although egalitarian parental care will lead to lower tolerance. There is a mismatch between theory and data: the almost complete lack of cases where individuals prefer to mate incestuously is at odds with a large overlap between the predicted range of inbreeding tolerance and estimates of inbreeding depression found in nature. We discuss four different solutions to this enigma, and suggest that inbreeding tolerance, where it is found, should not always be attributed to a simple constraint that has prevented finding any other mate.

Animals↗

[The effect of inbreeding on the manifestations of some physiological traits in the Kladrub Black Horse strain].

Inbreeding was used in the regeneration process in the breeding of the Kladrub Black Horse. Inbreeding rate is realized in practice, as related to the manifestation of the selected characteristics of this unique horse population. The evaluation of the effect of inbreeding on conception rate and fertility did not demonstrate any differences between the group of inbred mares and non-inbred mares. The study was conducted in mares used for breeding for 10 years. The results provide evidence that inbreeding causes no depression in this characteristics in the Kladrub Black Horse which would otherwise be the first physiological function in the reproduction process to be altered as a result of inbreeding. The evaluation of the effect of inbreeding on growth rate by comparing it with the standard growth curves which were characterized by the exponential function y = A (1 -- e-k(t-to)) did not indicate any statistically significant differences in growth dynamics between foals with a zero Fx value and inbred foals. This study was based on the evaluation of growth rate in the basic body traits and weight. It is inferred that inbreeding does not reduce growth dynamics of different body measurements and weight. Similarly, the evaluation of the body dimensions and weight of inbred and non-inbred adults showed no significant differences. Similar results were obtained from the evaluation of the relation between inbreeding and body constitution, character, and temperament. All the correlation coefficients are very low, almost equal to zero.

Animals↗

Effect of the bubonic plague epidemic on inbreeding in 14th century Britain.

The purpose of the study reported here was to further investigate a new method of estimating inbreeding in large, relatively isolated populations over historic times, as reported by Pattison (1999, 2001). The method is based on modeling the genealogical "paradox" and produces values of Pearl's coefficients of inbreeding as a function of time for any given population curve. In particular, this study demonstrates that the new method of estimating inbreeding may be used to examine the effect of unusual features in population curves on levels of inbreeding in that population. As an example, the medieval population "bump" that spans the 13th and 14th centuries in the population of Britain, which terminated abruptly with the outbreak of bubonic plague in 1348 AD, is examined. It is first assumed that the whole population was the adult (breeding) population, corresponding to minimum inbreeding. For this case it is found that, for distant generations, about 90% of the whole population occurs in any present-day British pedigree. This value compares favorably with the values of 85% and 80% reported by Wachter (1980) and Derrida et al. (1999, 2000), respectively. The population bump causes the curves for Pearl's coefficient, for minimum inbreeding, to have a plateau of about 96% over the period from about 1220 AD to 1380 AD. The effect of introducing a single known estimate of inbreeding into the model is to produce a more realistic situation where the adult (breeding) population is considerably less than the whole population. It is found that the maximum number of different ancestors in any generation, in the average British pedigree, is about 22900 individuals and occurs about 1220 AD. More importantly, and possibly contrary to expectation, it is now found that the population bump had virtually no effect on the level of inbreeding.

Consanguinity↗

Inbreeding depression and partial selfing: evolutionary implications of mixed-mating in a coastal endemic, silene douglasii var. oraria (Caryophyllaceae)

Recent studies have found moderate to high levels of selfing in plants despite high inbreeding depression. Because both factors influence the evolution and persistence of rare plants, we conducted glasshouse and field studies of pollination and inbreeding in Silene douglasii var. oraria, a perennial tetraploid endemic to coastal prairies. We detected: (i) variation in reproduction or inbreeding depression among life stages, years and maternal families; (ii) partial selfing yet higher relative fitness in outcrossed than selfed progeny; (iii) differing values of selfing and inbreeding depression using population means vs. matched maternal families. Fruit and seed production varied significantly with pollination treatment and year in flowers manipulated in situ during three seasons of growth. Hand-pollinations providing pollen in excess of ovule production in 1996 yielded more seeds than marked, open-pollinated flowers, implying pollen limitation of seed production. However, among-year differences in reproductive success after open-pollination (i.e. values equivalent to autogamy, selfing or outcrossing) suggest that pollination levels also vary temporally. In pollinations matched by maternal family, selfing yielded significantly fewer seeds than outcrossing. Fitness differences between inbred and outbred progeny were significant (P < 0.05) for seed production, percentage germination, and biomass or fecundity, but not for survival. Maternal family data gave selfing rates intermediate between obligate outcrossers and predominant selfers (S = 0.34-0.51), but population-wide means gave unusually high values (S = 1.1-1.6). Cumulative inbreeding depression was 76% for maternal families, and 70-85% using population means; in all cases, inbreeding depression values were high in early and late life stages, and lowest for survival. Thus far, reproductive assurance offers the most cogent explanation for the coexistence of moderate selfing and high inbreeding depression in this strongly protandrous Silene once thought to be highly outcrossing. This possibility merits further study in other rare plants with mixed-mating systems, where inbreeding depression and pollinator scarcity may both compromise population persistence and raise the threshold below which selfing is favoured by evolution.

Journal Article↗

The effect of drought stress on inbreeding depression in four populations of the Mediterranean outcrossing plant Crepis sancta (Asteraceae).

The effect of physiological stress on the magnitude of inbreeding depression in plants has been the subject of few studies and is currently controversial because of contradictory results. We measured the inbreeding depression at three drought stress levels, precisely defined by a preliminary physiological experiment. We also tested the hypothesis that more highly self-compatible populations exhibit reduced inbreeding depression due to purging of deleterious mutations. The study was conducted on two populations of the annual and allogamous plant Crepis sancta collected from the French Mediterranean region and two other populations from marginal areas with various self-incompatibility levels. Drought stress did not increase inbreeding depression in terms of plant mortality but significantly increased the inbreeding depression for the date of first flowering, number of heads per plant and relative growth rate. The most self-fertile marginal population showed an absence of inbreeding depression in most of the measured traits indicating that purging could have taken place in this population. The three others populations showed relatively low and similar estimates of inbreeding depression (delta approximately 0.35). The relatively low values obtained compared to the results found in allogamous plants suggests that the absence of competition for C. sancta in our experiment probably underestimated the effects of inbreeding in natural populations where competition occurs.

Analysis of Variance↗

Inbreeding and prereproductive mortality in the Old Order Amish. II. Genealogic epidemiology of prereproductive mortality.

The effects of offspring and parental inbreeding on prereproductive mortality (death before age 20 years) in the historical population of the Lancaster County, Pennsylvania, Old Order Amish were investigated using the Amish genealogic registry, which contains information on 42,465 births dating to the time of the pioneer migrants in the 1700s. Inbreeding coefficients for offspring and parents were computed using the path method of tracing common ancestors in the multigenerational pedigrees. In this population, prereproductive mortality declined from about 15% in the late 1800s to about 5% after 1930. Offspring inbreeding was found to be an independent predictor of prereproductive mortality after multivariate adjustment for demographic risk factors for mortality. Moreover, the higher the coefficient, the higher the relative risk of prereproductive death, and the higher the risk of multiple deaths in the same sibship. There was no evidence of declining inbreeding effects over 10 generations of continuous inbreeding, nor of any significant parental inbreeding effects. Because of the high levels of inbreeding, it could be shown that inbreeding accounts for about 40% of all prereproductive deaths in the present population. Genetic load analysis showed an average of about 1.7 lethal equivalents and a mostly mutational load.

Adult↗

Consequences of life history for inbreeding depression and mating system evolution in plants.

Many plants are perennial, but most studies of inbreeding depression and mating system evolution focus on annuals. This paper extends a population genetic model of inbreeding depression due to recessive deleterious mutations to perennials. The model incorporates life history and mating system variation, and multiplicative selection across many genetic loci. In the absence of substantial mitotic mutation, perennials have higher mean fitness and lower, or even negative, inbreeding depression than annuals with the same mating system. As in annuals, self fertilization exposes deleterious recessive mutations to selection, increasing mean fitness and decreasing inbreeding depression. Including mitotic mutation decreases mean fitness while increasing inbreeding depression. Perenniality introduces a kind of selective sieve, such that strongly recessive mutations contribute disproportionately to mean fitness and inbreeding depression. In the presence of high mitotic mutation, this selective sieve may provide a mechanistic basis for high inbreeding depression observed in some long lived perennials. Without substantial mitotic mutation, it is difficult to reconcile genetically based models of inbreeding depression with the empirical generalization that perennials outcross while related annuals self fertilize.

Biological Evolution↗

Inbreeding depression in anthropometric traits among Telaga boys of Kharagpur, West Bengal, India.

Inbreeding depression in phenotypic variations as well as reproductive capacity was reported in animals. Depression of physical measurements in human beings especially among infants and adults due to inbreeding has also been reported all over the world. The present study is an attempt to examine the nature of inbreeding effect on growing children at each yearly age with increase of inbreeding intensity in a local endogamous population based on pedigree data. In general, mean values of measurements appear to be smaller in higher levels of inbreeding from that of lower levels of inbreeding in each yearly age. These differences are even more marked when grouped as low and high inbreeding level. The percent of inbreeding depression tends to be larger in post adolescent boys than in younger children.

Adolescent↗

Inbreeding as measured by isonymy, pedigrees, and population size in Törbel, Switzerland.

Törbel provides an interesting test case for the study of the relationship between inbreeding measured by pedigrees and inbreeding measured by isonymy. At the start of this investigation, we were aware that isonymy could introduce biases into the calculation of the inbreeding coefficient in either direction. However, it was expected that in Switzerland, inbreeding from isonymy would be an overestimate due to patrilocal residence and polyphyletic names. One way of dealing with this problem [13] was not to be concerned with the absolute value of inbreeding but only in the difference between estimates. Any bias introduced in the estimate itself disappears in such comparisons, so that a trend of inbreeding can be ascertained correctly. However, it was considered equally important to subject several populations to both a complete pedigree analysis and an isonymic analysis to determine the relationship between estimates of inbreeding. Despite the fact that several authors (Swedlund [18], for example) warned users of isonymy to exercise caution, the careless application of isonymy still persists. In the present study, estimates of inbreeding from isonymy were brought into line with other methods based on pedigree analysis and population size. However, it was possible to do this only in Törbel where pedigree depth was extensive and relatively complete. Similar corrections are possible only when the distribution of mono- and polyphyletic names is known and when migration data are reliable. If the trouble is taken to make these corrections, the same time and effort might as well be spent in pedigree analysis (when fairly complete ascertainment is possible) to achieve the same end result.

Consanguinity↗

Detecting inbreeding depression in structured populations.

Measuring inbreeding and its consequences on fitness is central for many areas in biology including human genetics and the conservation of endangered species. However, there is no consensus on the best method, neither for quantification of inbreeding itself nor for the model to estimate its effect on specific traits. We simulated traits based on simulated genomes from a large pedigree and empirical whole-genome sequences of human data from populations with various sizes and structures (from the 1,000 Genomes project). We compare the ability of various inbreeding coefficients ([Formula: see text]) to quantify the strength of inbreeding depression: allele-sharing, two versions of the correlation of uniting gametes which differ in the weight they attribute to each locus and two identical-by-descent segments-based estimators. We also compare two models: the standard linear model and a linear mixed model (LMM) including a genetic relatedness matrix (GRM) as random effect to account for the nonindependence of observations. We find LMMs give better results in scenarios with population or family structure. Within the LMM, we compare three different GRMs and show that in homogeneous populations, there is little difference among the different [Formula: see text] and GRM for inbreeding depression quantification. However, as soon as a strong population or family structure is present, the strength of inbreeding depression can be most efficiently estimated only if i) the phenotypes are regressed on [Formula: see text] based on a weighted version of the correlation of uniting gametes, giving more weight to common alleles and ii) with the GRM obtained from an allele-sharing relatedness estimator.

Humans↗

Inbreeding in outport Newfoundland.

We investigated inbreeding in 3 outport Newfoundland study areas in which persistent genetic isolation was demonstrated previously. The inbreeding coefficient of every person born in each area was calculated from reconstructed pedigree data. The average inbreeding coefficient for persons born between 1960 and 1979 is 0.0032 in Trepassey Parish (southern Avalon Peninsula), 0.0171 for a group of communities on the west coast of the Great Northern Peninsula, and 0.0007 for southeastern Labrador. Average inbreeding of these populations was higher earlier in this century. Averages are high compared to those reported for other populations, consistent with genetic isolation. Coefficients of kinship were calculated for large samples of pairs of births in each study area, and frequency distributions of inbreeding coefficients compared with frequency distributions of kinship coefficients, to evaluate random and nonrandom mating with respect to consanguinity. These comparisons show that matings between unrelated individuals are more frequent than expected, that matings between first cousins are not strongly avoided in 2 of the 3 study areas, that matings between first cousins once removed are favored, and that matings between distantly related individuals are becoming more frequent. To gain an impression of the potential contribution of inbreeding to the prevalence of recessive disease, we calculated indirect estimates of the expected excess of prereproductive mortality due to inbreeding. These estimates are 15% for Trepassey Parish, 49% for the West Coast study area, and 2% for southeastern Labrador. It is unlikely that genetic isolation of outport Newfoundland populations will decrease. Elevated prevalences of recessive disease, due primarily to matings between persons unaware of their distant consanguinity, therefore require consideration in health care planning in Newfoundland.

Consanguinity↗

Selection for scrapie resistance and simultaneous restriction of inbreeding in the rare sheep breed "Mergellander".

Scrapie is a fatal infectious neurodegenerative disease for which susceptibility is associated with polymorphisms in the ovine prion protein (PrP) gene. Scrapie-eradication programmes are based on eliminating the susceptible VRQ allele and/or breeding for the resistant ARR allele. In rare breeds or breeds with a low frequency of the ARR allele this can lead to unacceptably high inbreeding rates with associated increased risk of genetic defects and inbreeding depression. The conservation status of populations with inbreeding rates (DeltaF) above 1% is considered critical. In the Dutch rare sheep breed the Mergellander animals carrying ARR alleles are closely related to one another, and could reach 1.53% when only ARR/ARR animals are used as parents. Inbreeding rates can be reduced by selecting the set of parents according to their average co-ancestry. We minimised inbreeding rates by calculating the optimal contribution of each ram and selection of ewes. This resulted in inbreeding rates of -0.17% with exclusive use of homozygous ARR rams, and -0.38% if use of heterozygous rams was allowed as well. Thus sophisticated breeding programs can prevent unacceptably high inbreeding rates when breeding for scrapie resistance.

Alleles↗

A simulation study on detecting purging of inbreeding depression in captive populations.

Inbreeding depression threatens the survival of small populations of both captive and wild outbreeding species. In order to fully understand this threat, it is necessary to investigate what role purging plays in reducing inbreeding depression. Ballou (1997) undertook such an investigation on 25 mammalian populations, using an ancestral inbreeding regression model to detect purging. He concluded that there was a small but highly significant trend of purging on neonatal survival across the populations. We tested the performance of the regression model that Ballou used to detect purging on independently simulated data. We found that the model has low statistical power when inbreeding depression is caused by the build-up of mildly deleterious alleles. It is therefore possible that Ballou's study may have underestimated the effects of ancestral inbreeding on the purging of inbreeding depression in captive populations if their inbreeding depression was caused mainly by mildly deleterious mutations. We also developed an alternative regression model to Ballou's, which showed an improvement in the detection of purging of mildly deleterious alleles but performed less well if deleterious alleles were of a large effect.

Alleles↗