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PubMed1980

A note on the frequency of consanguineous marriages in Reading, England in 1972/1973.

A random sample was taken of marriages celebrated in 1972/1973 in and around Reading, Berksshire, in order to investigate marital mobility and population structure. Respondents were asked whether they were related before marriage and isonymous marriages were noted. Eight consanguineous marriages were recorded. The inbreeding coefficient for the next generation is estimated to be 0.00017 from consanguineous marriages, 0.00021 from isonymy. These values are similar to those obtained from other modern Western societies.

Consanguinity↗

PubMed1989

Mortality of wild and captive chimpanzees.

Mortality of chimpanzees in the wild (Gombe National Park) and in captivity (Taronga Zoo, Sydney and Melbourne Zoo) was compared using standard cohort life table techniques. Overall mortality probabilities up to age 30 were compared using a logrank test. No significant difference in overall mortality was revealed, and the mortality curves did appear to be surprisingly similar, but there were nevertheless some differences in the distribution of mortality. Perinatal mortality was higher in the zoo, while post-perinatal and infant mortality were higher in the wild. Survivorship in the older zoo animals (over age 27) was better than the wild. These differences were attributed to the more sheltered zoo environment, including the availability of veterinary care, which could be expected to improve survival in infants and older adults. The higher perinatal mortality experienced by zoo infants could be reflecting higher levels of inbreeding among the zoo animals.

Animals↗

PubMedDate not supplied

Marker assisted selection with optimised contributions of the candidates to selection.

The benefits of marker assisted selection (MAS) are evaluated under realistic assumptions in schemes where the genetic contributions of the candidates to selection are optimised for maximising the rate of genetic progress while restricting the accumulation of inbreeding. MAS schemes were compared with schemes where selection is directly on the QTL (GAS or gene assisted selection) and with schemes where genotype information is not considered (PHE or phenotypic selection). A methodology for including prior information on the QTL effect in the genetic evaluation is presented and the benefits from MAS were investigated when prior information was used. The optimisation of the genetic contributions has a great impact on genetic response but the use of markers leads to only moderate extra short-term gains. Optimised PHE did as well as standard truncation GAS (i.e. with fixed contributions) in the short-term and better in the long-term. The maximum accumulated benefit from MAS over PHE was, at the most, half of the maximum benefit achieved from GAS, even with very low recombination rates between the markers and the QTL. However, the use of prior information about the QTL effects can substantially increase genetic gain, and, when the accuracy of the priors is high enough, the responses from MAS are practically as high as those obtained with direct selection on the QTL.

Genetic Markers↗

PubMedDate not supplied

A combination of walk-back and optimum contribution selection in fish: a simulation study.

The aim of this paper was to study the performance of a novel fish breeding scheme, which is a combination of walk-back and optimum contribution selection using stochastic simulation. In this walk-back selection scheme, batches of different sizes (50, 100, 1,000, 5,000 and 10,000) with the phenotypically superior fish from one tank with mixed families were genotyped to set up the pedigree. BLUP estimated breeding values were calculated. The optimum contribution selection method was used with the rate of inbreeding (DeltaF) constrained to 0.005 or 0.01 per generation. If the constraint on DeltaF could not be held, a second batch of fish was genotyped etc. Compared with the genotyping of all selection candidates (1000, 5,000 or 10,000), the use of batches saves genotyping costs. The results show that two batches of 50 fish were often necessary. With a batch size of 100, genetic level was 76-92% of the genetic level achieved for schemes with all fish being genotyped and thus candidates for the optimum contribution selection step. More parents were selected for schemes with larger batches, resulting in a higher genetic gain, especially when all selection candidates were genotyped. There was little extra genetic gain in genotyping of 1,000 fish instead of 100 for the larger schemes of 5,000 and 10,000 candidates. The accuracy of breeding values was similar for all batch sizes (approximately 0.30), but higher (approximately 0.5) when all candidates were included. Since only the phenotypically most superior fish were genotyped, BLUP-EBV were biased. Compared with genotyping of all selection candidates, the use of batches saves genotyping costs, while simultaneously maintaining high genetic gains.

Animals↗

PubMed2006

Efficient computation of the inverse of gametic relationship matrix for a marked QTL.

Best linear unbiased prediction of genetic merits for a marked quantitative trait locus (QTL) using mixed model methodology includes the inverse of conditional gametic relationship matrix (G-1) for a marked QTL. When accounting for inbreeding, the conditional gametic relationships between two parents of individuals for a marked QTL are necessary to build G-1 directly. Up to now, the tabular method and its adaptations have been used to compute these relationships. In the present paper, an indirect method was implemented at the gametic level to compute these few relationships. Simulation results showed that the indirect method can perform faster with significantly less storage requirements than adaptation of the tabular method. The efficiency of the indirect method was mainly due to the use of the sparseness of G-1. The indirect method can also be applied to construct an approximate G-1 for populations with incomplete marker data, providing approximate probabilities of descent for QTL alleles for individuals with incomplete marker data.

Algorithms↗

PubMed2006

Parallel computations on pedigree data through mapping to configurable computing devices.

Pedigree data structures have a number of applications in genetics, including the estimation of allelic or haplotype probabilities in humans and agricultural species, and the estimation of breeding values in agricultural species. Sequential algorithms for general purpose CPU-based computers are commonly used, but are inadequate for some tasks on large data sets. We show that pedigree data can be directly represented on Field Programmable Gate Arrays (FPGA), allowing highly efficient massively parallel simulation of the flow of genes. Operating on the whole pedigree in parallel, the transmission of genes can occur for all individuals in a single clock cycle. By using FPGA, the algorithms to estimate inbreeding coefficients and allelic probabilities are shown to operate hundreds to thousands of times faster than the corresponding sequentially based algorithms. Where problems can be largely represented in an integer form, FPGA provide an efficient platform for computations on pedigree data.

Algorithms↗

PubMed2004

A new set of BXD recombinant inbred lines from advanced intercross populations in mice.

BACKGROUND: Recombinant inbred (RI) strains are an important resource for mapping complex traits in many species. While large RI panels are available for Arabidopsis, maize, C. elegans, and Drosophila, mouse RI panels typically consist of fewer than 30 lines. This is a severe constraint on the power and precision of mapping efforts and greatly hampers analysis of epistatic interactions. RESULTS: In order to address these limitations and to provide the community with a more effective collaborative RI mapping panel we generated new BXD RI strains from two independent advanced intercrosses (AI) between C57BL/6J (B6) and DBA/2J (D2) progenitor strains. Progeny were intercrossed for 9 to 14 generations before initiating inbreeding, which is still ongoing for some strains. Since this AI base population is highly recombinant, the 46 advanced recombinant inbred (ARI) strains incorporate approximately twice as many recombinations as standard RI strains, a fraction of which are inevitably shared by descent. When combined with the existing BXD RI strains, the merged BXD strain set triples the number of previously available unique recombinations and quadruples the total number of recombinations in the BXD background. CONCLUSION: The combined BXD strain set is the largest mouse RI mapping panel. It is a powerful tool for collaborative analysis of quantitative traits and gene function that will be especially useful to study variation in transcriptome and proteome data sets under multiple environments. Additional strains also extend the value of the extensive phenotypic characterization of the previously available strains. A final advantage of expanding the BXD strain set is that both progenitors have been sequenced, and approximately 1.8 million SNPs have been characterized. This provides unprecedented power in screening candidate genes and can reduce the effective length of QTL intervals. It also makes it possible to reverse standard mapping strategies and to explore downstream effects of known sequence variants.

Animals↗

PubMed2002

Isonymy and isolation by distance in the Netherlands.

The isonymy structure of the Netherlands was studied using the surname distribution of 2.4 million private telephone users selected from a 1996 commercial CD-ROM containing the names of 6.3 million users in the country. The users were distributed in 226 towns selected on a geographic basis to form an approximately regular grid throughout the Netherlands. Names of telephone users in each town were downloaded from the CD-ROM, with private users being selected for inclusion in the analysis. The shortest linear distance between several nearest neighboring towns was less than 2 km (e.g., Kampen and Ijsselmuiden, Krommen and Zaandijk, Hendrikdo and Papendrecht) and the longest distance was 326 km (Delfzijl and Oostburg ZL). The number of different surnames revealed by the analysis was 126,485. Lasker's distance, the negative value of the logarithm of isonymy between localities, was found to be significantly correlated with linear geographic distance, with r = 0.47 +/- 0.006. A dendrogram built using the matrix of isonymy distances, using the nearest neighbor-joining method, separates the Dutch towns into several clusters, most of them correlated with traditional Dutch regions. Comparisons with the results of previous analyses of the structure of other European countries are given. From the present analysis, isolation by distance emerges clearly, and it is relevant, although much weaker than in Switzerland, Austria, Italy, and Germany. The random component of inbreeding estimated from isonymy indicates a considerable degree of homogeneity in the Netherlands.

CD-ROM↗

PubMed2003

Population structure of São Miguel Island, Azores: a surname study.

The knowledge of a population structure may constitute a powerful tool for mapping genes underlying susceptibility to Mendelian and complex diseases. To obtain a better understanding of the population structure of São Miguel Island (Azorean Archipelago, Portugal), we carried out a surname survey using the surnames listed in the most recent telephone book (2001). We identified 1315 different surnames in a total of 27,621 subscribers. The frequency of the different surnames was used to calculate the following parameters: isonymy (I), random component of inbreeding (FST), genetic diversity according to Fisher (alpha), migration rate according to Karlin-McGregor (v) and Nei's genetic distance. Eleven localities were selected, according to population size and geographic distribution, for analysis using the above parameters. Our results show that 51% of Salga's population and 52% of Sete Cidades's population are represented by six and eight surnames, respectively. These figures demonstrate the effective isolation of these two small places, which are located at opposite ends of São Miguel Island. Salga, Achada, and Sete Cidades present the lowest values of Fisher's alpha, indicating less genetic diversity. In contrast, the capital, Ponta Delgada, presents the highest value of alpha (78.13), indicating more genetic diversity. Our data indicate that the clustering of the localities corresponds to the geographic features of the island, where localities close together tend to share similar surnames. In conclusion, the population of São Miguel is relatively homogeneous and may constitute an ideal model for genetic mapping studies.

Azores↗

PubMed2001

Spontaneous neoplasms in captive African cane rats (Thryonomys swinderianus Temminck, 1827).

Despite the increasing importance of cane rat (Thryonomys swinderianus) farming in Africa, diseases of these animals in captivity are not well known. A survey of a colony in Gabon averaging 235 cane rats over a period of 36 months allowed the observation of several suspected tumors and the confirmation of three cases of neoplasms. Within a period of 8 months, a chondroma in an adult female, a hemangiosarcoma in a subadult male, and a chondrosarcoma in an elderly female were diagnosed. This incidence (1.3%) of neoplasms in the cane rat colony in such a short period is uncommon. Neoplasms in rodents might be induced by such factors as a high inbreeding coefficient, an oncogenic virus, or chemical agent intoxication. Although the etiology remains undetermined, these cases are described to provide baseline data on the pathology of this species in captivity.

Animals↗

PubMed2006

Bayesian estimation of the timing and severity of a population bottleneck from ancient DNA.

In this first application of the approximate Bayesian computation approach using the serial coalescent, we demonstrated the estimation of historical demographic parameters from ancient DNA. We estimated the timing and severity of a population bottleneck in an endemic subterranean rodent, Ctenomys sociabilis, over the last 10,000 y from two cave sites in northern Patagonia, Argentina. Understanding population bottlenecks is important in both conservation and evolutionary biology. Conservation implications include the maintenance of genetic variation, inbreeding, fixation of mildly deleterious alleles, and loss of adaptive potential. Evolutionary processes are impacted because of the influence of small populations in founder effects and speciation. We found a decrease from a female effective population size of 95,231 to less than 300 females at 2,890 y before present: a 99.7% decline. Our study demonstrates the persistence of a species depauperate in genetic diversity for at least 2,000 y and has implications for modes of speciation in the incredibly diverse rodent genus Ctenomys. Our approach shows promise for determining demographic parameters for other species with ancient and historic samples and demonstrates the power of such an approach using ancient DNA.

Animals↗

PubMed2006

Selection for heterozygosity gives hope to a wild population of inbred wolves.

Recent analyses have questioned the usefulness of heterozygosity estimates as measures of the inbreeding coefficient (f), a finding that may have dramatic consequences for the management of endangered populations. We confirm that f and heterozygosity is poorly correlated in a wild and highly inbred wolf population. Yet, our data show that for each level of f, it was the most heterozygous wolves that established themselves as breeders, a selection process that seems to have decelerated the loss of heterozygosity in the population despite a steady increase of f. The markers contributing to the positive relationship between heterozygosity and breeding success were found to be located on different chromosomes, but there was a substantial amount of linkage disequilibrium in the population, indicating that the markers are reflecting heterozygosity over relatively wide genomic regions. Following our results we recommend that management programs of endangered populations include estimates of both f and heterozygosity, as they may contribute with complementary information about population viability.

Animals↗

PubMed1998

Characteristics of the semen of three endangered species of gazelles (Gazella dama mhorr, G. dorcas neglecta and G. cuvieri).

As part of a captive breeding programme for three species of endangered gazelles (Gazella dama mhorr, G. dorcas neglecta and G. cuvieri) the semen parameters for each species were characterized. The volume of ejaculated semen varied widely within species (G. dama: 565-5569 microliters; G. dorcas: 0-1454 microliters; G. cuvieri: 50-1411 microliters), as did sperm concentration (G. dama: 14-1629 x 10(6) ml-1; G. dorcas: 197-2836 x 10(6) ml-1; G. cuvieri: 228-927 x 10(6) ml-1). Sperm motility and viability were high in the three species. G. dama had a significantly lower proportion of normal spermatozoa, with a significantly higher proportion having abnormal heads and midpieces and more spermatozoa with cytoplasmic droplets. In addition, G. dama tended to have a lower proportion of spermatozoa with normal acrosomes. Sperm heads in G. dama and G. cuvieri were pear-shaped, whereas they were oval in G. dorcas. Spermatozoa from G. cuvieri were the longest. These data were also analysed in the context of three hypotheses that could explain inter-species differences in semen characteristics. Differences in testes size were due largely to differences in body size between species. However, no semen characteristic could be explained by allometric relationships. The three gazelle species differed in the intensity of sperm competition (as measured by relative testes mass), a factor that could explain differences in the proportion of normal spermatozoa. Finally, although the three species have reached different levels of inbreeding, this factor did not explain differences in semen characteristics in the population.

Animals↗

PubMed2005

Kin selection is implicated in partial sib-mating populations with constant viability differences before mating.

The change in the frequency of a rare mutant allele under constant sex-differentiated viability selection in an infinite, partial full-sib mating population is studied. The diplo-diploid and haplo-diploid polygynous models are considered with a Poisson distribution for the number of offspring produced by every mated female. Reproduction is followed by weak selection among the offspring and then mating to form the next generation. It is shown that the rate of change with respect to the frequency of the mutant allele and the intensity of selection can be expressed in terms of costs or benefits of substituting the mutant type for the wild type, which correspond to average excesses in viability in females and males, multiplied by coefficients of relatedness to the individuals affected by such a substitution and reproductive values associated to the sexes of these individuals. This reveals hidden interactions between mated individuals and between males for mating, the former having positive effects on the reproductive success of related individuals and the latter having negative effects. Such interactions are the result of reproductive constraints when a fixed proportion of females must mate with a male sib and all females are fertilized as long as one mate is available. However, they affect the change in allele frequency because there is inbreeding or relatedness between mates and more generally relatedness between interacting individuals. Surprisingly, the effects of these interactions cancel out in a diploid population when the number of offspring is large enough so that the possibility for a female to have no male sib to mate with can be neglected and the viability differences are the same in both sexes.

Algorithms↗

PubMed2005

Epistasis in monkeyflowers.

Epistasis contributes significantly to intrapopulation variation in floral morphology, development time, and male fitness components of Mimulus guttatus. This is demonstrated with a replicated line-cross experiment involving slightly over 7000 plants. The line-cross methodology is based on estimates for means. It thus has greater power than the variance partitioning approaches historically used to estimate epistasis within populations. The replication of the breeding design across many pairs of randomly extracted, inbred lines is necessary given the diversity of multilocus genotypes residing within an outbred deme. Male fitness is shown to exhibit synergistic epistasis, an accelerating decline in fitness with inbreeding. Synergism is a necessary, but not sufficient, condition for a mutational deterministic hypothesis for the evolutionary maintenance of sexual reproduction. Unlike male fitness measures, flower morphology and development time yield positive evidence of epistasis but not of synergism. The results for these traits suggest that epistatic effects are variable across genetic backgrounds or sets of interacting loci.

Crosses, Genetic↗

PubMed2005

Positive assortative mating with family size as a function of predicted parental breeding values.

While other investigations have described benefits of positive assortative mating (PAM) for forest tree breeding, the allocation of resources among mates in these studies was either equal or varied, using schemes corresponding only to parental rank (i.e., more resources invested in higher-ranking parents). In this simulation study, family sizes were proportional to predicted midparent BLUP values. The distribution of midparent BLUP values was standardized by a constant, which was varied to study the range of distributions of family size. Redistributing progenies from lower- to higher-ranking families to a point where an equal number of progenies were still selected out of each family to the next generation caused minimal change in group coancestry and inbreeding in the breeding population (BP), while the additive genetic response and variance in the BP were both greatly enhanced. This generated additional genetic gains for forest plantations by selecting more superior genotypes from the BP (compared to PAM with equal family sizes) for production of improved regeneration materials. These conclusions were verified for a range of heritability under a polygenic model and under a mixed-inheritance model with a QTL contributing to the trait variation.

Analysis of Variance↗

PubMed2006

Increase of the spontaneous mutation rate in a long-term experiment with Drosophila melanogaster.

In a previous experiment, the effect of 255 generations of mutation accumulation (MA) on the second chromosome viability of Drosophila melanogaster was studied using 200 full-sib MA1 lines and a large C1 control, both derived from a genetically homogeneous base population. At generation 265, one of those MA1 lines was expanded to start 150 new full-sib MA2 lines and a new C2 large control. After 46 generations, the rate of decline in mean viability in MA2 was approximately 2.5 times that estimated in MA1, while the average degree of dominance of mutations was small and nonsignificant by generation 40 and moderate by generation 80. In parallel, the inbreeding depression rate for viability and the amount of additive variance for two bristle traits in C2 were 2-3 times larger than those in C1. The results are consistent with a mutation rate in the line from which MA2 and C2 were derived about 2.5 times larger than that in MA1. The mean viability of C2 remained roughly similar to that of C1, but the rate of MA2 line extinction increased progressively, leading to mutational collapse, which can be ascribed to accelerated mutation and/or synergy after important deleterious accumulation.

Animals↗

PubMed2006

Unexpected high polymorphism at the FABP4 gene unveils a complex history for pig populations.

Fatty acid bing protein 4 (FABP4) plays a key role in fat regulation in mammals and is a strong positional candidate gene for the FAT1 quantitative trait locus located on porcine chromosome 4. DNA resequencing of the FABP4 gene region in 23 pigs from 10 breeds and wild boar revealed 134 variants in 6.4 kb, representing a silent nucleotide diversity of piS=0.01, much higher than reported so far in animal domestic species. Moreover, this diversity was highly structured. Also strikingly, the FABP4 phylogenetic tree did not show any geographical or breed origin clustering, with distant breeds sharing similar haplotypes and some of the most heterozygous samples pertaining to highly inbred animals like Iberian Guadyerbas (inbreeding coefficient approximately 0.3) or British Tamworth. In contrast, the cytochrome b (mtDNA) phylogenetic tree was coherent with geographical origin. The estimated age of the most recent common ancestor for the most divergent Iberian or Tamworth haplotypes was much older than domestication. An additional panel of 100 pigs from 8 different breeds and wild boar from Spain, Tunisia, Sardinia, and Japan was genotyped for seven selected single nucleotide polymorphisms and shows that high variability at the porcine FABP4 is the rule rather than the exception. Pig populations, even highly inbred, can maintain high levels of variability for surprisingly long periods of time.

Animals↗