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Genetic analysis of discrete reproductive traits in sheep using linear and nonlinear models: II. Goodness of fit and predictive ability.

The performance of linear and nonlinear sire and animal models in the analyses of reproductive traits (fertility, litter size, and ovulation rate) in two sheep populations (Rambouillet and Finnsheep) was compared in terms of goodness of fit and predictive ability. Linear sire (LSM) and animal (LAM) models were used with all traits. Nonlinear models were the threshold, Poisson, and negative binomial. Threshold sire (TSM) and animal (TAM) models were also used with all traits. Litter size and ovulation rate were analyzed also with Poisson and negative binomial sire (PSM and NBSM, respectively) and animal (PAM and NBAM, respectively) models. Variance components were those reported in the companion article. For PAM a new set of variance components derived from estimates found with the linear animal model also was used (PAM-L). Mean squares error (MSE) and correlations between fitted and observed values were used to assess goodness of fit. Predictive ability was assessed by partitioning the data sets for the different traits into two subsets with the restriction that all levels of fixed effects were represented in each subset. Parameters from one subset were employed to predict observations in the other, and then MSE and correlations between observed and predicted values were used as criteria for model comparison. Within estimation procedure, breed, and trait, goodness of fit of sire and animal models was similar. Linear and threshold models resulted in similar fit, and both outperformed Poisson and negative binomial models. In terms of predictive ability, linear and threshold models performed only slightly better than Poisson and negative binomial models. Goodness of fit and predictive ability generally were better when models included permanent environmental effects.

Animals↗

Genetic parameter estimates for reproductive traits of male and female littermate swine.

Reproductive traits of purebred and crossbred pigs produced in a four-breed diallel mating system using the Duroc, Landrace, Spotted and Yorkshire breeds were collected for five consecutive farrowing seasons (two farrowing seasons/year) beginning in fall 1976. Paternal half-sib heritabilities and genetic correlations for testicular traits (120 boars from 36 sires), serum testosterone (TE) and luteinizing hormone (LH) concentrations before and after treatment with gonadotropin releasing hormone (GnRH; 131 boars from 37 sires) and breeding performance traits (151 boars from 38 sires) were estimated. Heritability estimates were generally small to moderate except for sperm/gram testis (SGT), LH concentrations before (LHO) and at 3 h (LH3) after treatment with GnRH (.73 +/- .48, .61 +/- .46 and 1.19 +/- .45, respectively). A large positive genetic correlation was found for LHO with LH3 (.94 +/- .39), while a negative relationship existed for LH3 with TE concentrations at 3 h after GnRH injection. The genetic correlation between a boar's average first service conception rate and average conception rate also was significant (.82 +/- .54). Genetic correlations among littermate traits would suggest that selection for decreased age at puberty in gilts could cause an increase in LH concentrations in boar offspring, before and after GnRH injection, and may also have adverse effects on their ability to settle females. Selection for increased weight at puberty of gilts could cause TE concentrations of boar offspring to increase while having little effect on their breeding performance.

Animals↗

Genetics of growth and reproduction in the turkey. 13. Effects of repeated backcrossing of an egg line to two sire lines.

The objective of the present study was to determine the feasibility of rapidly increasing the BW of dam lines by repeated backcrossing of a dam line to a sire line. A line (E) selected long-term for increased egg production was backcrossed to a line (F) selected long-term for increased 16-wk BW (BC1) and to a commercial sire line (BC2). The BW of the F and commercial sire lines were about twice as large as that of the E line. Egg production of the E line was more than double the egg production of either of the sire lines. Large gains in BW and breast width were observed in both backcrosses. Based on additive genetic variation, gains in BW were less than expected in the first generation for females in the BC1 and for both sexes in the BC2. Values observed for males of the BC1 were similar to expected values at 8 and 16 wk and larger than expected values at 20 wk of age. Slower than expected BW gains in Generation 1 may have been attributable to the small egg size of E females. After Generation 1, BW at 16 and 20 wk of age were equal to, or greater than, expected. Egg production was reduced in both backcrosses relative to the E line. Fertility and hatchability were reduced relative to the E line by backcrossing in BC1 but not in BC2. Results of the present study suggest limited repeated backcrossing of a dam line to a sire line may be an economically feasible method to greatly increase the BW of dam lines without unduly sacrificing reproduction capability.

Aging↗

The biological significance of meiosis.

Four possible biological functions of meiosis are considered. First, the conventional view that it generates by recombination and sexual reproduction the genetic diversity on which natural selection can act. Second, that recombination at meiosis plays an important role in the repair of genetic defects in germ line cells. Third, that it is essential, at least in animals, for the reprogramming of gametes which give rise to the fertilized egg. Fourth, that it helps maintain the immortality of the germ line, possible by a process of rejuvenation involving the removal of faulty RNA and protein molecules, or by the elimination of defective meiocytes. A unified hypothesis is proposed which attempts to link these diverse functions. Evidence is now available which strongly indicates that the control of gene activity in higher organisms depends in part on the pattern of cytosine methylation in DNA, and that this pattern is inherited through the activity of a maintenance methylase. Epigenetic defects may arise by the loss of methyl groups which the methylase is unable to replace in somatic and also germ line cells, if de novo methylation cannot occur. There is also evidence that recombination at meiosis is largely confined to structural genes or adjacent DNA. It is proposed that the absence of a functionally important methyl group in a promotor or operater region produces a recombinator or signal for the initiation of recombination. The formation of hybrid DNA in this region then allows the lost methyl groups to be replaced by maintenance methylase activity. The removal of epigenetic defects by recombination during meiosis therefore becomes an essential part of a reprogramming and rejuvenation process. Assuming some epigenetic defects are nevertheless transmitted to the next generation, sexual reproduction and outbreeding would be advantageous because they provide the opportunity for their removal at the next meiosis. Inbreeding would be disadvantageous, because it increases the probability that epigenetic defects would become homozygous and could no longer be removed by recombination.

5-Methylcytosine↗

Preimplantation diagnosis after assisted reproduction techniques for genetically-determined male infertility.

One hundred and thirty-six cycles with a poor prognosis for full-term pregnancy underwent preimplantation genetic diagnosis (PGD) of aneuploidy. The mean maternal age was 31.8 +/- 2.5 years. Only patients younger than 36 years were included in the study with the aim of evaluating whether sperm indices have an effect on the chromosomal constitution of preimplantation embryos. No differences were detected in the percentage of aneuploid embryos; however a higher incidence of monosomies and trisomies was found in MESA-TESE embryos compared to the group of normospermic patients. In addition, an increase in the proportion of gonosomal aneuploidy seemed to be associated with the severity of the male factor parameters. The rate of de-novo chromosomal abnormalities in embryos from patients with a normal karyotype suggested an increased frequency proportional to the severity of the male factor condition, the proportion of monosomic and trisomic embryos, and the percentage of gonosomal aneuploidy increased accordingly. In the case of couples with a male altered karyotype, comparable frequency of chromosomally abnormal embryos, and monosomy and trisomy were observed irrespective of semen indices, gonosomal aneuploidy was only observed in one case where the patient had a karyotype with gonosomal mosaicism. These data confirm that the severe male infertility condition determines an increase in the rate of de-novo abnormalities, as anticipate by the follow-up of the children born after ICSI.

Adult↗

Modification of heat-shock gene expression in Drosophila melanogaster populations via transposable elements.

We report multiple cases in which disruption of hsp70 regulatory regions by transposable element (TE) insertions underlies natural variation in expression of the stress-inducible molecular chaperone Hsp70 in Drosophila melanogaster. Three D. melanogaster populations from different continents are polymorphic for jockey or P element insertions in the promoter of the hsp70Ba gene. All three TE insertions are within the same 87-bp region of hsp70Ba promoter, and we suggest that the distinctive promoter architecture of hsp genes may make them vulnerable to TE insertions. Each of the TE insertions reduces Hsp70 levels, and RNase protection assays demonstrate that such insertions can reduce transcription of the hsp70Ba gene. In addition, the TEs alter two measures of organismal fitness, inducible thermotolerance and female reproductive success. Thus, transposition can create quantitative genetic variation in gene expression within populations, on which natural selection can act.

Analysis of Variance↗

Computer simulation model of swine production systems: III. A dynamic herd simulation model including reproduction.

A dynamic herd simulation model for a swine production unit has been developed. The model is discrete and stochastic and the appropriate random distributions have been defined from the literature or empirically estimated. Theoretical concepts and relationships presented previously are used to simulate growth and the overall life cycle of individual animals. Simulated animals are young pigs (from birth to slaughter age), gilts, and sows. Animal events are farrowing, weaning, mating, end-nursery (transfer from nursery to the growing-finishing facility), and slaughter and are processed individually using a next-event scheduling orientation package. Animals within the herd are culled for different health and reproductive reasons. Genetic parameters, diet composition, and herd management are input variables chosen by the user. The effects of nutrition, genetics, season, and other factors on several reproductive parameters are considered. Model evaluation is performed by studying the output of the model under specified herd situations. The herd model adequately simulates animal flow and dynamics of the herd.

Animal Nutritional Physiological Phenomena↗

Not just for experts: the public debate about reprogenetics in Germany.

When reproductive and genetic technologies spurred an extended German policy debate, the issues at stake went beyond the technologies to include the very meaning of "ethics" and the respective roles of ethicists and of the public in thinking about ethical questions.

Bioethical Issues↗

Cystic fibrosis newborn screening: impact on reproductive behavior and implications for genetic counseling.

OBJECTIVE: To evaluate the impact of newborn screening for cystic fibrosis (CF) on the reproductive knowledge and behavior of CF families and to determine if heterozygote detection with the immunoreactive trypsinogen (IRT) method in conjunction with DNA analysis (IRT/DNA) influences knowledge and attitudes about reproduction in false-positive families. METHODS: The Wisconsin CF Neonatal Screening Project investigated 650 340 infants from 1985 to 1994 in a comprehensive randomized controlled trial to study both benefits and risks of newborn screening and to determine if early diagnosis would improve the prognosis of children with CF. Assessments of reproductive knowledge, attitudes, and behaviors of 135 families of children diagnosed as having CF in both the early treatment group and control groups were made 3 months after diagnosis using a questionnaire which was completed by 100 families. The same questionnaire was administered 1 year later to evaluate retention of information. It was completed by 71 families. A follow-up assessment tool was also administered in 1994 and responses obtained from 73 families. Knowledge, attitudes, and behavior among false-positive families were also assessed at the time of the sweat test in 206 families who experienced IRT screening and 109 families tested with the IRT/DNA method. Follow-up assessments were completed 1 year later in 106 IRT families and 63 IRT/DNA families. RESULTS: In families with a CF child, 95% initially understood that there was a 1 in 4 risk in subsequent pregnancies, and there was good retention of this information 1 year later. At the 1994 assessment, 52% of families had not yet conceived more children, but 74% of these already had children. In the couples in whom CF was diagnosed in the first child, 70% (95% confidence interval = 54% to 85%) conceived more children. There were 43 subsequent pregnancies in 31 families. Prenatal diagnosis was used by 26% of the families (8/31) for 21% of the pregnancies (9/43). There were 3 pregnancies with CF detected, all of which were carried to term. In the false-positive groups, >95% of families initially understood that their child definitely did not have CF. There was no difference between false-positive IRT and IRT/DNA groups, and the information was retained at 1 year. Follow-up assessment 1 year after negative sweat tests revealed that 7% of the IRT and 10% of the IRT/DNA families still thought about the results often or constantly. When asked whether the experience of screening affected feelings about having more children, an affirmative response was obtained in 4% of IRT families but in 17% of IRT/DNA families. One year later, more than half of the false-positive IRT/DNA families did not understand that they were at increased risk of having a child with CF. CONCLUSIONS: We conclude that CF neonatal screening does not have a significant impact on the reproductive behavior of most families and that prenatal diagnosis is not used by the majority of CF families. IRT/DNA testing experiences seem to affect attitudes about having more children, and some parents are confused about the implications of the results, even with genetic counseling. However, persistent concerns about the sweat test result are limited. Questions raised by this study confirm the need for more research regarding the process of genetic counseling and its impact on reproductive attitudes and behavior in the newborn screening setting.

Cystic Fibrosis↗

Study of LH response to GnRH in the young male as a criterion of genetic merit for female reproduction in sheep.

A high and a low response line in sheep were selected on the basis of the mean concentration of LH in 10-week-old Finn-Dorset ram lambs after an i.v. injection of 5 micrograms GnRH. After 8 male generations the mean LH response of the high line was more than 5-fold that of the low line and the heritability of the selected trait was estimated at 0.44 +/- 0.015. Highly significant line differences in mean LH response to GnRH were also found in males at 20 weeks of age and females at 10 and 20 weeks of age and the genetic correlations between the four LH response traits appear to be close to unity. Large line differences in the mean FSH response to GnRH were also found in both males and females at 10 and 20 weeks of age. Selection had little effect on the physical characteristics of lambs. High-response line ewes entering their first breeding season at about 7 months of age showed oestrus earlier in the season and had higher ovulation rates and numbers of lambs born per ewe lambing than did low-response line ewes. In the second breeding season, at about 19 months of age, the only line difference was a higher ovulation rate early in the breeding season in high-line ewes. It is suggested that these changes may be mediated by a more rapid response in high-line ewes to increased GnRH stimulation at puberty or at the beginning of the breeding season.

Animals↗

Evaluation of subchronic (13 week), reproductive, and in vitro genetic toxicity potential of 2-ethylhexyl-2-cyano-3,3-diphenyl acrylate (Octocrylene).

Use of 2-ethylhexyl-2-cyano-3,3-diphenyl acrylate (Octocrylene) in commercial sunscreen products has increased considerably in recent years. To support larger scale human exposure to this compound, additional toxicological information was needed in several key areas. The present studies evaluated subchronic toxicity, developmental toxicity, and in vitro genotoxic potential of Octocrylene. In the subchronic study, male and female New Zealand white (NZW) rabbits treated topically with concentrations of octocrylene up to 534 mg/kg/day for 13 weeks showed slight to moderate dose-dependent skin irritation that correlated positively with a mild depression in body weight gain. Lack of associated histopathologic or clinical hematology abnormalities suggested that the body weight effect probably reflected a nonspecific response to topical irritation. In percutaneous developmental toxicity studies, NZW does were treated topically with Octocrylene at levels up to 267 mg/kg/day on Days 6 through 18 of gestation. Body weight gain, food consumption, and all maternal, reproductive, and offspring parameters evaluated were comparable between Octocrylene-treated and control animals. In the oral developmental toxicity assay, female CD-1 mice received oral doses of Octocrylene up to 1000 mg/kg/day on Days 8-12 of gestation. No evidence of maternal or developmental toxicity was seen at any dose tested. Genotoxicity was evaluated in vitro using the Chinese hamster ovary cell assay to assess clastogenicity and the mouse lymphoma cell assay to assess forward gene mutations. Octocrylene did not induce any significant increase in genotoxicity. This evaluation of toxicological potential supports the use of Octocrylene as a human photoprotectant.

Acrylates↗

Molecular and genetic dissection of a reproductive isolation gene, zygotic hybrid rescue, of Drosophila melanogaster.

Hybrids from the cross between males of Drosophila melanogaster and females of its sibling species (D. simulans, D. mauritiana, or D. sechellia) are embryonic lethal when they carry the wild type allele of zygotic hybrid rescue (zhr) from D. melanogaster. The zhr gene has been mapped in the proximal region of the X heterochromatin slightly distal to the proximal breakpoint of In(1)sc8, the region rich in 1.688 g/cm3 satellite DNA. Since this satellite DNA does not exist in the sibling species, the satellite DNA was considered to be involved in the hybrid lethality. We examined the hypothesis molecular cytogenetically. The results are (1) three Df(1)zhr chromosomes carried this satellite DNA, and (2) hybrids were viable even if the amount of the satellite DNA in hybrids was increased by adding minichromosomes Dp(1;f)1205 and Dp(1;f)1187 into the genome. These results do not support the above hypothesis.

Alleles↗

Reproductive isolation in Drosophila: how close are we to untangling the genetics of speciation?

Our understanding of the genetic basis of reproductive isolation in Drosophila has progressed rapidly over the past decade. Details of the genetic structure of hybrid sterility have been revealed and a general consensus has been reached concerning the genetic bases of Haldane's rule. Genetic analyses now reach beyond hybrid sterility and inviability, allowing us to make important comparisons across different traits involved in reproductive isolation. Expansion of genetic studies to include rescue of hybrid incompatibilities has opened the door for more detailed molecular and developmental analyses of reproductive isolation than has ever before been possible.

Animals↗