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Genetic selection strategies: computer modeling.

There are four primary factors to consider in genetic selection strategies: 1) accuracy of selection, 2) selection intensity, 3) effective population size, and 4) mating system. Current theory indicates that optimum response to selection is achieved by maximizing the first three factors and using a mating systems that allows optimization of reproductive characteristics in dam lines and production characteristics in sire lines. However, with limited resources, compromises among the first three factors are needed. Simulations are useful for examining those compromises. Unrealistic simplifying assumptions are necessary for analytic theoretical results and thus do not address real world breeding problems. Using simulations, the relationship between selection accuracy, which is increased by use of family selection indices or Best Linear Unbiased Prediction (BLUP), and response to selection was examined. Results show that those procedures place a great restriction on effective population size, which offsets most of their advantage, i.e., there is too little emphasis on effective population size. A revision of the methodology and a reappraisal of the results of selection theory for optimization of genetic response is required. Another relationship that is of fundamental importance in breeding programs is that between selection intensity and effective population size. Analytical results for the additive case have been developed but have never been extended to heterotic traits. A gene level simulation program was developed to examine that relationship. Results show that the optimal selection strategy depends on the trait being selected. For additive traits and in the short term (20 generations), one should maximize selection intensity. For heterotic traits, an intermediate proportion (25% of each sex) gives optimal response. In all breeding strategies, primary attention must be given to the rate of inbreeding, which is increased by increasing either accuracy of selection or selection intensity. Inbreeding reduces response to selection in two ways. First, for both additive and nonadditive traits, inbreeding is a measure of the amount of random genetic drift that has occurred. Genetic drift causes loss of favorable alleles. Once lost, those alleles can never be recovered and thus genetic drift lowers the selection limit. Second, for heterotic traits, inbreeding results in a depression of the mean caused by directional dominance.

Animals↗

What should we weigh to estimate heterozygosity, alleles or loci?

The interest to study the effects of inbreeding in natural populations has increased in the last years. Several microsatellite-derived metrics have recently been developed to infer inbreeding from multilocus heterozygosity data without requiring detailed pedigrees that are difficult to obtain in open populations. Internal relatedness (IR) is currently the most widespread used index and its main attribute is that allele frequency is incorporated into the measure. However, IR underestimates heterozygosity of individuals carrying rare alleles. For example, descendants of immigrants paired with natives (normally more outbred) bearing novel or rare alleles would be considered more homozygous than descendants of native parents. Thus, the analogy between homozygosity and inbreeding that generally is carried out would have no logic in those cases. We propose an alternative index, homozygosity by loci (HL) that avoids such problems by weighing the contribution of each locus to the homozygosity index depending on their allelic variability. Under a wide range of simulated scenarios, we found that our index (HL) correlated better than both IR and uncorrected homozygosity (H(O)), measured as proportion of homozygous loci) with genome-wide homozygosity and inbreeding coefficients in open populations. In these populations, which are likely to prevail in nature, the use of HL instead of IR reduced considerably the sample sizes required to achieve a given statistical power. This is likely to have important consequences on the ability to detect heterozygosity fitness correlations assuming the relationship between genome-wide heterozygosity and fitness traits.

Alleles↗

Selection on individual phenotype and best linear unbiased predictor of breeding value in a closed swine herd.

Computer simulation of a closed 100-sow and 4-boar swine herd was used to analyze effects of selection method on genetic change, inbreeding and genetic variance over 10 yr for traits with heritabilities (h2) of .10, .30 and .60. Selection of replacement animals was either on individual phenotype or best linear unbiased predictor (BLUP) of breeding value using an animal model. For both methods, culling of existing breeding animals was at random on age and reproductive performance. The effect of additional culling of existing breeding animals when a replacement with better individual phenotype or BLUP of breeding value was available also was evaluated. Genetic gain was greater for selection on BLUP than on individual phenotype, but relative differences narrowed with increasing heritability. At yr 10 the relative advantage of selection on BLUP was 55% for h2 = .10, 25% for h2 = .30 and 10% for h2 = .60. Culling when a replacement with better individual phenotype or BLUP of breeding value was available resulted in considerably increased genetic progress (34% to 57%). The proportional effect of culling on rate of genetic gain was relatively independent of heritability and type of selection. Inbreeding (F) was higher with selection on BLUP (F = .27 to .38 at yr 10) than on individual phenotype (F = .17 to .22 at yr 10). As heritability increased, rate of inbreeding increased for selection on individual phenotype, but rate of inbreeding tended to decrease with increasing heritability for selection on BLUP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Husbandry↗

External form and internal anatomy of Holsteins and Jerseys.

Body weights, external dimensions, and postmortem measures of internal body dimensions or weights of organs and glands of Holsteins and Jerseys were used to establish norms, interrelationships of traits, and effects of sire and inbreeding on changes in external form. Sires differed in nearly all measures of external body form. Sire effects increased with advancing age whereas effects of inbreeding (greater than 12.5, 3.0 to 12.4, or less than 3.0% of inbreeding) declined. Skeletal dimensions were smallest in the greater than 12.5% inbred group. Differences due to inbreeding were largest at 3 and 6 mo of age and in first lactation. Body heights and head dimensions were nearer to mature size at 3 and 6 mo than other measures. In both breeds, most rapid development was between 3 and 6 mo, but Jersey matured 1 to 2% faster. Age (2 to 3, 4 to 5, 6 to 10, greater than 10 yr) was significant for most postmortem measurements. Correlations among measures of external form were .30 to .93. Correlations between external form and internal features or between internal dimensions and organs were lower. External and internal features were positively correlated, but few external features showed strong enough association with internal features for use as predictors of size of organs, glands, or digestive capacity.

Age Factors↗

Self-pollination and its costs in a monoecious fig (Ficus aurea, Moraceae) in a highly seasonal subtropical environment.

The unusual floral phenology of most monoecious figs, related to their highly specialized pollination mutualism with agaonid wasps, combines pronounced dichogamy at the level of inflorescences and individuals with population-level asynchrony in flowering. This floral phenology ensures that outcrossing strongly predominates. Fig populations may thus be expected to possess deleterious recessive alleles that lead to inbreeding depression when selfing does occur. However, whether monoecious figs are self-compatible and whether selfing results in inbreeding depression have never been investigated. Using wasps as "pollination tools" and exploiting infrequent overlap in male and female phases on the same tree, we conducted controlled selfed and outcrossed pollination experiments in Ficus aurea. Our results show that this species is totally self-compatible. No negative effects of selfing could be demonstrated on syconium retention, number of vacant ovaries, seed set, or seed germination. However, wasp production had a tendency to be higher after self-pollination. While it is possible that inbreeding depression is expressed at later developmental stages, its absence at the early stages we examined is nonetheless surprising for a plant expected to be highly outcrossed. It is likely that selection pressures other than avoidance of inbreeding are responsible for the evolution and maintenance of the unusual floral phenology of figs.

Journal Article↗

Cardiovascular risk factors and relatedness in an Icelandic subpopulation.

Theoretical and empirical studies suggest adverse effects of inbreeding on general vigour. The genetic architecture of physiological and biochemical cardiovascular risk factors is, furthermore, an unsolved issue. Our aim with this study is to investigate potential effects of inbreeding on stated risk factors in a relatively well demarcated Icelandic subpopulation. We used genealogical records to calculate coefficient of inbreeding and estimated the potential association of the coefficient with stated risk factors with known statistical methods. The results suggest absence of inbreeding depression with exception of HDL cholesterol.

Blood Glucose↗

[The RYR1 genotype of Chinese inbred pigs].

OBJECTIVE: Porcine stress syndrome (PSS) is one kind of molecular genetics defect diseases of pig which will cause malignant hyperthermia syndrome (MHS) and is the first index should be excluded in screening of a pig species for xenotransplantation. It was reported that mutation of pig rynodine receptor(RYR1) gene is the main reason for PSS. In this study, RYR1 genotypes of the Chinese Banna mini pig inbred line and inbreeding closed colony Wuzhishan pig were investigated with polymerase chain reaction-restriction endonuclease fragment length polymorphism (PCR-RFLP) technique. METHODS: Antevenocaval whole blood samples were collected from 50 Banna mini-pig inbred-line(BMI), 15 inbreeding Wuzhishan pig (WZSP) and 25 Neijiang pigs (NJP) as negative control, the primer were designed and synthesized, PCR reaction was conducted following the sequence of 94 degrees C (1 min), 58 degrees C (1 min) and 72 degrees C (1 min) for 30 cycles. The PCR products were digested with restriction endonuclease HhaI and then electrophoresis check. RESULTS: A 659 bp DNA fragment was amplified with these two primers, the HALNN sample fragment was cut into fragments as 493 bp and 166 bp individually after the digestion, indicates no point mutation at site 1,843 in RYR1 gene in all tested BMI pig and WZSP. Namely, the RYR1 genotype of 50 cases of BMI and 15 cases of WZSP were HALNN, therefore their phenotype is PSS negative. CONCLUSION: It indicates that the genotype of Banna mini pig inbred line and inbreeding Wuzhishan pig are HALNN therefore PSS absolutely negative, the group penetrance is 0. This is consistent with experimental observation. It suggests that Banna mini pig inbred line and inbreeding Wuzhishan pig may be the alternative donor for xenotransplantation.

Animals↗

The frequency of consanguineous matings due to multiple use of donors in artificial insemination.

The amount of inadvertent inbreeding as a result of donor anonymity in artificial insemination has been estimated. A child from a first-cousin mating or closer is expected approximately once every 41/2 years in the United States as a result of artificial insemination by donor. Since a child with unknown paternity seems less likely to mate with paternal relatives than is a child with known paternity, artificial insemination by donor may actually reduce the average inbreeding of the population. Nevertheless, to reduce recessive diseases, inbreeding should be kept to a minimum by limiting the number of children produced by a single donor. Formulas are presented for local risks of inbreeding based on the number of children per donor.

Consanguinity↗

Genetic implications of mating structure in a Caribbean isolate.

Mating patterns in the population of St. Barthélémy, French West Indies, are examined to evaluate the expected genetic consequences of consanguinity avoidance and of failure to mate due to celibacy and emigration. Nearly 60% of all individuals reaching mating age on "St. Bart" never contribute to the gene pool of succeeding generations. This greatly reduces the effective population size and, therefore, increases genetic drift or random inbreeding. The consequent loss of heterozygosity is partially countered by the fact that the individuals who fail to reproduce within the population tend to be more closely related to the population than are those who do reproduce. This nonrandom failure to mate results in nonrandom inbreeding, which reduces total pedigree inbreeding. Total inbreeding is also reduced by consanguinity avoidance. However, the effect of avoiding close consanguineous matings is, to some extent, reversed by an apparent preference for more distant relationships, especially with second cousins. Generally similar results are found for the related Northside French population of St. Thomas. U.S. Virgin Islands. A recently developed mathematical model predicts the expected effect on heterozygosity of partial or complete avoidance of, or preference for, any combination of consanguineous matings, and also takes into account nonrandom failure to mate. Application of this model to these two populations suggests that under some circumstances nonrandomness in celibacy and emigration may have a greater influence on genotype distributions than does consanguinity avoidance.

Consanguinity↗

Human genetic studies in areas of high natural radiation. VIII. Genetic load not related to radiation.

The genetic load disclosed by inbreeding has been analyzed in a multiple regression model for a population involving several localities in the state of Espírito Santo, Brazil. The inbreeding load has been estimated for number of pregnancies, abortions, stillbirths, children born alive, anomalies in general, sex ratio, infant mortality, post-infant mortality, and sterility and infertility of the couple. There was no evidence of either maternal or paternal inbreeding effects on the variables analyzed. The effect of inbreeding of the zygote was significant only for anomalies in general (B = 2.29 +/- 0.45) and infant mortality (B = 3.19 +/- 1.39). The latter result must be accepted with caution because of the many environmental causes affecting infant mortality. The B/A ratio suggested a predominantly mutational load for anomalies in general (B/A = 25), but with respect to infant mortality (B/A = 6), the ratio is regarded as an underestimate because of the environmental contribution to A and therefore not supportive of the segregational interpretation.

Abnormalities, Radiation-Induced↗

Association studies in consanguineous populations.

To study the genetic determinism of multifactorial diseases in large panmictic populations, a strategy consists in looking for an association with markers closely linked to candidate genes. A distribution of marker genotypes different in patients and controls may indicate that the candidate gene is involved in the disease. In panmictic populations, the power to detect the role of a candidate gene depends on the gametic disequilibrium with the marker locus. In consanguineous populations, we show that it depends on the inbreeding coefficient F as well. Inbreeding increases the power to detect the role of a recessive or quasi-recessive disease-susceptibility factor. The gain in power turns out to be greater for small values of the gametic disequilibrium. Moreover, even in the absence of gametic disequilibrium, the presence of inbreeding may allow to detect the role of a recessive factor. Ignoring inbreeding when it exists may lead to reject falsely a recessive model if the mode of inheritance is inferred on the distribution of genotypes among patients.

Case-Control Studies↗

Evolution of consanguinity in the Archbishopric of Santiago de Compostela (Spain) during 1900-1979.

We present a study of the frequencies of the different types of consanguineous marriages, up to the level of second cousins, using as a source the ecclesiastical dispensations given from 1900 to 1979 in the Archbishopric of Santiago de Compostela (Galicia, Spain). We also report the rate of consanguinity, the average coefficient of inbreeding, and its evolution. From 1900 to 1979, 15,739 consanguineous marriages were registered, corresponding to 25 different categories of relationship. The rate of consanguinity of the total number of consanguineous marriages is 5.13% and the average coefficient of inbreeding is 1.94 x 10(-3), values that are within the wide range of variability found in other Spanish populations. Spain is characterized, with regard to the rest of Western Europe, by a high level of inbreeding with a late and rapid decrease in this factor. The most relevant aspect of the structure of consanguinity lies in the high frequency of marriages between close relatives: 0.16% uncle-niece or aunt-nephew marriages and 1.62% marriages between first cousins, both values with respect to the total number of marriages. This phenomenon appears to be generalized throughout northern Spain. The evolution of the total consanguinity lends itself to a polynomial curve model. The fitted curve of the evolution of the average coefficient of inbreeding has an ascending branch and a descending branch, with the inflection point situated in the year 1918; the regression lines, for both the ascending and the descending branches, have regression coefficients significantly different from 0 (p < 0.001).

Catholicism↗

Changes over 100 years in degree of isolation of 21 parishes of the Lima Valley, Italy, assessed by surname isonymy.

Changes over 100 years (1887-1986) in degree of isolation of 21 parishes of the Lima valley, Italy, were assessed using surname analysis. Crow and Mange's inbreeding coefficients and Lasker and Kaplan's repeated pair values were calculated using 8026 marriage records; temporal changes were assessed by dividing birth cohorts into 4 time periods of 25 years each: 1887-1911, 1912-1936, 1937-1961, and 1962-1986. Analysis was carried out at 2 hierarchical levels: the population of the valley as a whole and the valley's subdivision into 21 parishes. The relationship between population size and level of isonymy during the breakdown of isolates was investigated. The results show that there is a small difference in inbreeding coefficients between the first 2 periods at either hierarchical level of analysis and a substantial decrease in marital isonymy during the study period is mostly due to the change in male random isonymy. Furthermore, the Fn value at the higher hierarchical level almost coincides with the mean F value at the lower hierarchical level, indicating that over time the parish remained the fundamental reproductive unit. Regression analysis showed that geographic isolation became increasingly important in differentiation among the parishes in population size and in levels of inbreeding. The marked deviation from equilibrium between drift and migration that characterizes the breakdown of isolates of almost all the rural populations is an important disturbing factor in assessing the relationship between level of inbreeding and population size. Comparison over time allows us to better describe the evolutionary forces at the basis of the changes in genetic structure of a population.

Cohort Studies↗

A study of some genetic characteristics of the Fur and Baggara tribes of the Sudan.

The average inbreeding coefficients of the highly consanguineous Fur and Baggara tribes of Western Sudan were 0.04167 and 0.04450, respectively. Two hundred ninety-eight subjects from the two tribes were tested for polymorphism of hemoglobins, seven red cell enzymes, and four serum proteins. The Baggara showed a higher gene frequency of HbS and TfD and lower gene frequency of GdA and PC compared to the Fur. Both tribes showed a low gene frequency of PGM1 and high frequency of G6PD deficiency when compared to other Sudanese tribes. In spite of the high degree of inbreeding, no significant deviation from the Hardy-Weinburg equilibrium was observed in either tribe. The effects of inbreeding seem to be offset by mixing between the two tribes on Gabal Marra Plateau. The flow of the sickle gene from the Baggara into the Fur and other Sudanese tribes is discussed.

Acid Phosphatase↗

Genetic load in an isolated tribal population of South India.

The Kota of Nilgiri Hills, Tamilnadu, are an isolated tribal population and occupy the lowest stratum in the local social hierarchy. They have developed an economic symbiotic relationship with other tribes of the Nilgiri Hills (e.g., Toda, Kurumba, Badaga), but have almost no social relationship with other communities, such as the Hindu and Muslim, communities, etc. The total population of the Kota is about 1200. Consanguineous marriages are highly favoured in this group. This paper presents data on prenatal, infant and adolescent mortality in relation to the degree of inbreeding. No perceptible difference has been found in mortality figures between consanguineous and non-consanguineous marriages. This may be due to the long history of inbreeding among the Kota. No case of visible congenital malformation has been noticed. The estimates of genetic load as revealed by inbreeding data indicate that genetic load in the Kota is low (perhaps about 1 lethal equivalent per gamete); it is also low in comparison with that in other Indian populations.

Abortion, Spontaneous↗

Telomere-associated RFLPs and electrophoretic karyotyping reveal lineage relationships among race-specific strains of Ustilago hordei.

The inheritance of telomere-associated restriction fragment length polymorphisms (tel-RFLP) and chromosome-length polymorphisms (CLPs) were criteria used for the identification of strains of Ustilago hordei that form a direct lineage. Teliospore collections of race 8 strains and strains reported to be derived from race 8 through inbreeding were used in these analyses. None of the race 8 strains examined in this study, representing three consecutive inbred generations, was polymorphic for any terminal BamHI and BglII chromosomal loci, nor did they have any apparent CLPs. Strains from a teliospore collection obtained in 1971 and designated 447, representing the first inbred generation of race 8 strains and a shift to increased virulence on cultivar Hannchen, had tel-RFLP arrays indistinguishable from the race 8 strains isolated in this study; and they had no obvious CLPs. Strains from the presumed second inbred generation, the 1279 teliospore line, which was pathogenic on six additional cultivars, had numerous CLPs and a tel-RFLP array that differed from race 8 strains at more than 50% of the terminal chromosomal BamHI and BglII restriction sites. The tel-RFLP array of each 1279 strain was identical and indistinguishable from the arrays of strains representing races 10 and 13, indicating that they share a direct lineage. A race 14 strain, also presumed to be derived from race 8 strains by inbreeding, had a unique tel-RFLP array and an electrophoretic karyotype that distinguished it from all other strains. The tel-RFLP arrays alone eliminate the 1279 and race 14 strains from being direct descendants from race 8 strains by inbreeding and suggest that this approach can identify a strain lineage among other inbred sexually reproducing fungi, or isolates that comprise different asexual clonal populations.

Blotting, Southern↗

Reversed selection responses in small populations of the housefly (Musca domestica L.).

We compared the efficacy of artificial and natural selection processes in purging the genetic load of perpetually small populations. We subjected replicate lines of the housefly (Musca domestica L.), recently derived from the wild, to artificial selection for increased mating propensity (i.e., the proportion of male-female pairs initiating copulation within 30 min) in efforts to cull out the inbreeding depression effects of long-term small population size (as determined by a selection protocol for increased assortative mating). We also maintained parallel non-selection lines for assessing the spontaneous purge of genetic load due to inbreeding alone. We thus evaluated the fitness of artificially and 'naturally' purging populations held at census sizes of 40 individuals over the course of 18 generations. We found that the artificially selected lines had significant increases in mating propensity (up to 46% higher from the beginning of the protocol) followed by reversed selection responses back to the initial levels, resulting in non-significant heritabilities. Nevertheless, the 'naturally' selected lines had significantly lower fitness overall (a 28% reduction from the beginning of the protocol), although lower effective population sizes could have contributed to this effect. We conclude that artificial selection bolstered fitness, but only in the short-term, because the inadvertent fixation of extant genetic load later resulted in pleiotropic fitness declines. Still, the short-term advantage of the selection protocol likely contributed to the success of the speciation experiment since our recently-derived housefly populations are particularly vulnerable to inbreeding depression effects on mating behavior.

Animal Population Groups↗

Effects of coancestry on accuracy of individual assignments to population of origin: examples using Great Lakes lake trout (Salvelinus namaycush).

Methods for assigning individuals to population of origin are widely used in ecological genetics, resources management, and forensics. Characteristics of genetic data obtained from putative source populations that enhance accuracy of assignment are well established. How non-independence within and among unknown individuals to be classified [i.e., gene correlations within individual (inbreeding) and gene correlations among individuals within group (coancestry)] affect assignment accuracy is poorly understood. We used empirical data for six microsatellite loci and offspring from full-sib crosses of hatchery strains of lake trout (Salvelinus namaycush; Salmonidae) representing known levels of coancestry (mean theta = 0.006 and 0.06) within families to investigate how gene correlations can affect assignment. Additional simulations were conducted to further investigating the influence of allelic diversity (2, 6 or 10 alleles per locus) and inbreeding (F = 0.00, 0.05, and 0.15) on assignment accuracy for cases of low and high inter-population variance in allele frequency (mean F (st) = 0.01 and 0.1, respectively). Inbreeding had no effect on accuracy of assignments. In contrast, variance in assignment accuracy across replicated simulations, and for each empirical case study increased with increasing coancestry, reflecting non-independence of probabilities of correct assignment among members of kin groups. Empirical estimates of assignment error rates should be interpreted with caution if appreciable levels of coancestry are suspected. Additional emphasis should be placed on sampling designs (spatially and temporally) that define or minimize the potential for sampling related individuals.

Animal Population Groups↗