Genetic analysis of rumination time based on an analysis of 77,697 Israeli dairy cows.

Reduction of methane emission may become necessary for sustainable milk production. Several studies indicate a relationship between rumination time and the level of methane emission. The objectives of the current study were to estimate environmental factors affecting daily rumination time in high-yielding dairy cattle, genetic parameters for rumination time across parities, and environmental and genetic correlations between rumination time and economic traits, and to predict the consequence of inclusion of this trait in the Israeli breeding index. The data included more than 30 million daily records from 77,697 Israeli Holstein cows for rumination time and milk production. A lactation measure of daily rumination time per cow was computed as the mean of the residuals from a linear model analysis with rumination time as the dependent variable. The independent variables were parity and the square root, linear, quadradic and inverse of DIM by parity. Because of the shape of the lactation curve for rumination time, separate linear model analyses were performed for records up to 40 DIM and records with >40 DIM. The phenotypic correlation between first- and second-parity lactations for rumination time was almost 0.8, and close to 0.7 for milk. The heritability of lactation rumination time was close to 0.44 for parities 1 to 3. Heritability for milk production decreased from 0.5 in first parity to 0.3 in third parity. For both traits, genetic correlations among parities were all >0.9. Thus, for routine genetic analysis of rumination time, records in the different parities can be considered the same trait. The genetic correlation between rumination time and milk on first parity was 0.25 and increased slightly with increase in parity. Genetic correlations between rumination time, based on the first 40 DIM, were economically unfavorable with retained placenta but economically favorable with metritis, ketosis, and displaced abomasum. Genetic correlations between rumination time and the 9 traits included in the Israeli breeding index (milk, fat, and protein production; SCS; female fertility; herd-life; milk production persistency; calving ease; and calf mortality) were all economically favorable, except for the correlation of 0.17 with SCS. With the current index, daily rumination time with a current mean of 536 min and SD of 90 min is expected to increase by 11 min/d after 10 yr of selection. Inclusion of this trait with a positive index weight equivalent to 10% of the index should increase rumination time by 19 min. All changes in expected gains due to inclusion of rumination time in the index were economically positive, except for fat and SCS. Inclusion of rumination time in the index should result in 1 kg less gain in fat, a miniscule gain of 0.03 for SCS; and gains of 1.5 kg protein, 0.3% female fertility, and 5 d herd-life. Even though the case for a genetic correlation between rumination time and methane emission is still weak, inclusion of this trait in the commercial index may be justified, considering that equipment is now commercially available for routine recording at reasonable cost.

Genetic and Genomic Analysis of Cow Mortality in the Israeli Holstein Population.

"Livability" was defined as the inverse of the probability of death. The objectives of this study were to estimate the heritability, genetic and phenotypic trends for the livability of Israeli Holstein cows; estimate the genetic and environmental correlations between livability and the nine traits included in the Israeli breeding index; estimate the effect of the inclusion of livability in the Israeli breeding index on expected genetic gains; and compute a genome-wide association study (GWAS) for livability. Seven data sets were analyzed. All data were derived from the database of the Israeli dairy cattle herd-book. The mean livability for the complete data set of 523,954 cows born from 2000 through 2016 was 89.6%. Pregnancy reduced livability by 15%. Livability generally increased with parity and days in milk within parity. Heritability of livability was 0.0082. Phenotypic and genetic trends over the 14-year period from 2000 through 2013 were -0.42% and -0.22% per year. If livability is included in the Israeli breeding index, accounting for 9% of the index, livability would increase by 1.3% and protein production would decrease by 11 kg over the next decade, as compared to the current index. A marker in proximity to the oxytocin-vasopressin locus had the greatest effect in the GWAS. Oxytocin activity in cattle affects calving-associated pathologies and maternal death. Inclusion of livability in the Israeli breeding index is not recommended.

Breeding Dairy Cattle for Female Fertility and Production in the Age of Genomics.

Phenotypic and genetic changes for female fertility and production traits in the Israeli Holstein population over the last three decades were studied in order to determine if long term selection has resulted in reduced heritability and negative genetic correlations. Annual means for conception status, defined as the inverse of the number of inseminations to conception in percent, decreased from 55.6 for cows born in 1983 to 46.5 for cows born in 2018. Mean estimated breeding values increased by 1.8% for cow born in 1981 to cows born in 2018. Phenotypic records from 1988 to 2016 for the nine Israeli breeding index traits were divided into three time periods for multi-trait REML analysis by the individual animal model. For all traits, heritabilities increased or stayed the same for the later time periods. Heritability for conception status was 0.05. The first parity genetic correlation between conception status and protein yield was -0.38. Heritabilities decreased with the increase in parity for protein but remained the same for conception status. Realized genetic trends were greater than expected for cows born from 2008 through 2016 for somatic cell score, conception status and herd-life, and lower than expected for the production traits.

Genomic Prediction of Complex Traits in Animal Breeding with Long Breeding History, the Dairy Cattle Case.

In accordance with the infinitesimal model for quantitative traits, a very large number of genes affect nearly all economic traits. In only two cases has the causative polymorphism been determined for genes affecting economic traits in dairy cattle. Most current methods for genomic evaluation are based on the "two-step" method. Genetic evaluations are computed by the individual animal model, and functions of the evaluations of progeny-tested sires are the dependent variable for estimation of marker effects. With the adoption of genomic evaluation in 2008, annual rates of genetic gain in the US increased from ∼50-100% for yield traits and from threefold to fourfold for lowly heritable traits, including female fertility, herd-life and somatic cell concentration. Gradual elimination of the progeny test scheme has led to a reduction in the number of sires with daughter records and less genetic ties between years. As genotyping costs decrease, the number of cows genotyped will continue to increase, and these records will become the basic data used to compute genomic evaluations, most likely via application of "single-step" methodologies. Less emphasis in selection goals will be placed on milk production traits, and more on health, reproduction, and efficiency traits and "environmentally friendly" production. Genetic variance for economic traits is maintained by increase in frequency of rare alleles, new mutations, and changes in selection goals and management.

Genetic and genomic analysis of age at first insemination in Israeli dairy cattle.

We performed a genetic analysis of age at first insemination, including estimation of the heritability and genetic correlations with other economic traits, and the consequences of including this trait in the Israeli selection index. The genetic factors affecting age at first insemination were determined via GWAS. Five data sets were analyzed. Data sets 1, 2, and 3 were used to compute variance components among age at first insemination, first calving age, days from first insemination to calving, and the 9 traits included in the Israel breeding index. Heritabilities for age at first insemination, calving age, and days from first insemination to calving in Israeli Holsteins as computed by REML individual animal model analyses of 273,239 Israeli Holstein cows were 0.072, 0.042, and 0.014. The estimated genetic correlation between the first 2 traits was 0.88. In addition to the fact that heritability of age at first insemination is 1.7 times the heritability for calving, the former trait has the advantage that the number of records is greater, and the records are generated earlier. Absolute values of the genetic and residual correlations between age at first insemination and the 9 traits included in the Israeli index were all less than 0.2. Data set 4 included first insemination dates of 1,181,600 calves born from 1985 through 2018. Genetic evaluations were computed by a single trait animal model. Annual phenotypic and genetic trends for age at first calving for calves born since 1985 were "positive," that is, economically negative, at 0.320 ± 0.003 and 0.169 ± 0.005 d, respectively. Applying the GCTA-GREML software, 54% of variance in the transmitting ability of 1,585 sires could be explained by considering all 40,498 markers included in the GWAS analysis. The significant markers were mainly associated with milk production genes. The SNP UA-IFASA-8854 on chromosome 11 had the lowest probability value, 1.2 × 10-24. This marker is located between the genes RETSAT and ELMOD3, both of which are overexpressed in human mammary glands. The gene RETSAT is reported to be essential for lipid accumulation and adipogenesis promotion. Gene enrichment analysis found that genes in the genomic region flanking significant markers are associated with vasopressin receptor activity, which was shown to mediate puberty in humans. If age at first insemination is included in the index with a weighting to account for 9% of the index, reductions of 2.8 and 2.6 d for age at first insemination and first calving age after 10 yr of selection are predicted, as compared with reductions of 1.4 and 1.1 d with the current index. Gains for the other index traits are only marginally affected. We suggest selection on age at first insemination as an alternative to selection for early calving.

Broad phenotypic impact of the effects of transgenerational heat stress in dairy cattle: a study of four consecutive generations.

BACKGROUND: Global warming has increased the frequency of heat stress in livestock. Although heat stress directly leads to negative effects on production and reproduction traits in dairy cattle, the transgenerational transition of these changes is poorly understood. We hypothesized that heat stress in pregnant cows might induce epigenetic modifications in the developing embryo germ cells, which, in turn, might lead to phenotypic effects in the offspring. Here, we examined whether transgenerational effects of heat stress contribute to the phenotypic expression of economic traits in Israel dairy cattle. Since heat stress in Israel occurs specifically between June and October, first we examined the association of the month of birth of F1 cows (pregnancy of the F0 dam) with the performance of the F2 and F3 female offspring. Then, we calculated an annual heat stress index and examined the association of the heat stress index during the pregnancy of the F0 dam with the performance of her F2 and F3 offspring. Finally, we examined intergenerational interactions of heat stress by comparing the performance of F3 cows according to the pregnancy seasons of the F0 and F1 animals. RESULTS: We found a significant association of the month of birth, season of pregnancy, and heat stress index of F0 females, with the performance of their F2 and F3 progenies, which suggests a true transgenerational effect. The most significant transgenerational effects were on fat yield and concentration, dystocia, still-birth, and maturation. CONCLUSIONS: These findings suggest that heat stress during pregnancy affects the performance of offspring, regardless of life circumstances in at least the last three generations. Therefore, heat stress can reduce selection efficiency in breeding programs and may have economic significance in livestock.

Genetic and Genome-Wide Association Analysis of Yearling Weight Gain in Israel Holstein Dairy Calves.

Yearling weight gain in male and female Israeli Holstein calves, defined as 365 × ((weight - 35)/age at weight) + 35, was analyzed from 814,729 records on 368,255 animals from 740 herds recorded between 1994 and 2021. The variance components were calculated based on valid records from 2008 through 2017 for each sex separately and both sexes jointly by a single-trait individual animal model analysis, which accounted for repeat records on animals. The analysis model also included the square root, linear, and quadratic effects of age at weight. Heritability and repeatability were 0.35 and 0.71 in the analysis of both sexes and similar in the single sex analyses. The regression of yearling weight gain on birth date in the complete data set was -0.96 kg/year. The complete data set was also analyzed by the same model as the variance component analysis, including both sexes and accounting for differing variance components for each sex. The genetic trend for yearling weight gain, including both sexes, was 1.02 kg/year. Genetic evaluations for yearling weight gain was positively correlated with genetic evaluations for milk, fat, protein production, and cow survival but negatively correlated with female fertility. Yearling weight gain was also correlated with the direct effect on dystocia, and increased yearling weight gain resulted in greater frequency of dystocia. Of the 1749 Israeli Holstein bulls genotyped with reliabilities >50%, 1445 had genetic evaluations. As genotyping of these bulls was performed using several single nucleotide polymorhphism (SNP) chip platforms, we included only those markers that were genotyped in >90% of the tested cohort. A total of 40,498 SNPs were retained. More than 400 markers had significant effects after permutation and correction for multiple testing (pnominal < 1 × 10-8). Considering all SNPs simultaneously, 0.69 of variance among the sires' transmitting ability was explained. There were 24 markers with coefficients of determination for yearling weight gain >0.04. One marker, BTA-75458-no-rs on chromosome 5, explained ≈6% of the variance among the estimated breeding values for yearling weight gain. ARS-BFGL-NGS-39379 had the fifth largest coefficient of determination in the current study and was also found to have a significant effect on weight at an age of 13-14 months in a previous study on Holsteins. Significant genomic effects on yearling weight gain were mainly associated with milk production quantitative trait loci, specifically with kappa casein metabolism.

Genetic and environmental analysis of female calf survival in the Israel Holstein cattle population.

The objectives were to estimate the effects of various environmental factors on female calf survival of Israeli Holsteins, to estimate the economic value of calf survival under Israeli conditions, to estimate the genetic and environmental variance components for calf and cow survival using the individual animal model, to perform GWAS analyses of survival to first calving and herd life after first calving, to estimate the genetic and environmental trends for calf survival since 1985, to estimate genetic correlations of calf survival with the traits included in the current Israeli breeding index, and to estimate the consequences of inclusion of calf survival in the national selection index. Mean calf survival rate of Israeli Holsteins from 2001 through 2008 was 0.85, and the mean economic value of survival to first calving was $526. Birth month, gestation length, dystocia, and twin birth significantly affected calf survival rate. Dystocia and twin birth each reduced survival rate by 0.034. Survival rate was highest for calves born in October and lowest for calves born in February. The difference between these months was 3.4%. Maximum survival was at a gestation length of 276 d, the mean gestation length for this population. Survival rate was reduced to 0.76 for calves born after a gestation length of 260 d. The individual animal model was applied for all the genetic analyses. Heritability for calf survival to first calving, as estimated by REML, was 0.009, whereas heritability of herd life from first calving was 0.15. The complete data set for genetic analysis of survival to first calving included 1,235,815 calves born between 1985 and 2017. Annual genetic and phenotypic trends for calf survival were 0.019 and 0.015%, respectively. Correlations of transmitting abilities of 226 sires born since 2010 for calf survival with the traits included in the Israeli breeding index were significant only for the maternal effects of dystocia and stillbirth. The GWAS analysis was based on the transmitting abilities of 1,493 bulls with genotypes and reliabilities >0.5 for calf survival and cow herd life. There were 7 single nucleotide polymorphisms with coefficients of determination >0.03 for calf survival and 12 single nucleotide polymorphisms with coefficients of determination >0.05 for cow survival. There was no overlap between the genome-wide significant markers for the GWAS analyses of calf survival and cow herd life. This corresponds to the conclusion from the REML results and the low correlations between the sire evaluations that the genetic control of the 2 traits are not similar. Inclusion of calf survival in the Israeli breeding would result in a 0.5% increase in calf survival over 10 yr but reduce progress for the other traits by 8%.

Genetic and genomic analysis of long insemination interval in Israeli dairy cattle as an indicator of early abortions.

One of the causes of observed low fertility is embryo loss after fertilization. Previous findings suggested that more than half of fertilizations result in embryo loss before pregnancy is detected. We proposed reinsemination between 49 and 100 d after the first insemination as an indicator trait for early abortion (EA) in dairy cattle based on the mean estrus interval of 21 d. This trait was compared with conception rate from first insemination and conception status, computed as the inverse of the number of inseminations to conception. Animal model variance components were estimated by REML, including parents and grandparents of cows with records. First-parity heritability for first insemination conception rate was 3%. In the multitrait analysis of parities 1 to 3 for putative EA, heritabilities ranged from 8.9% for first parity to 10.4% for second parity. All genetic correlations were >0.9, whereas all environmental correlations were <0.12. The variance component for the service sire effect for putative EA rate was less than half the variance component for conception rate. Thus, genetic control of the 2 traits is clearly different, and analysis of EA rate by a single-trait animal model is justified. Genetic evaluation for putative EA was computed using this model, including all first- through third-parity cows with freshening dates from January 1, 1985, through December 31, 2016, that either became pregnant on first insemination or were reinseminated between 49 and 100 d after the first insemination. All known parents and grandparents of cows with records were included in the analysis. The regression of the breeding value for non-abortion rate on the cows' birth year was 0.083%/yr. The genetic correlation between first-parity EA and conception status was 0.995. The genetic correlations between first-parity EA and milk, fat, and protein production were all negative, whereas the genetic correlation between EA and herd life was 0.33. Inclusion of putative EA in the selection index instead of conception status resulted in 10 to 20% greater genetic gain for both fertility traits. In a genome-wide association study based on 1,200 dairy bulls with reliabilities >50% for abortion rate genotyped for 41,000 markers, 6 markers were found with nominal probabilities of <10-12 to reject the null hypothesis of no effect on EA rate. The markers with the lowest probabilities for EA rate were also included among the markers with the lowest probabilities for female fertility, but not vice versa. The marker explaining the most variance for abortion rate is located within the ABCA9 gene, which is found within an ATP-binding cassette (ABC) genes cluster. The ABC family is the major class of primary active transporters in the placenta.

Mapping of the Sex Determining Region on Linkage Group 12 of Guppy (Poecilia reticulata).

Poecilia reticulata is one of the most popular ornamental fish species with a higher demand for males due to their large colorful fins. The objectives of this study were mapping of the sex-determining (SD) region on linkage group 12 of guppy, and identification of a sex specific marker. We generated eight polymorphic microsatellite markers distributed along the distal 5.4 Mbp sequence of the previously identified SD region on linkage group (LG) 12. The markers were tested for association with sex in 156 individuals of the Red Blonde and Flame strains, and 126 progeny of four full-sibs Red Blonde families. A male-specific allele was found for microsatellite gu1066 at position of 25.3 Mbp on LG12 for both strains, and gu832 at position 24.4 Mbp for the Flame strain. Thus, a region of 0.9 Mbp between these markers, harboring 27 annotated genes, was selected for analysis. Based on association of copy number variation and sex determination we mapped a duplicated region between LGs 9 and 12, of 1.26 Mbp, containing 59 genes on LG12. The common interval between the segment bounded by gu1066 and gu832, and the duplicated region of 0.43 Mbp on LG12 harbors 11 genes of which 6 have multiple copies (54%). Growth arrest and DNA damage inducible gamma-like (GADD45G-like) is a plausible positional and functional candidate gene for its role in male fertility. We characterized the genomic structure of the gene in guppy, and found two isoforms; but no sex-biased differences were evident in genomic sequence and gene expression.

Genetic and environmental analysis of diseases with major economic impact in Israeli Holsteins.

Incidences of ketosis, metritis, mastitis, and retained placenta were studied in Israeli Holstein cows calving between 2008 and 2017. These diseases were selected based on their economic impact. Ketosis, metritis, and retained placenta were scored dichotomously. Mastitis was scored as absent, a single occurrence during the lactation, or more than 1 occurrence. Ketosis and metritis were recorded during the first 21 d after calving, retained placenta during the first 5 d after calving, and mastitis up to 305 d in milk. The effects of herd-year-season, calving age, month of calving, gestation length, and occurrence of dystocia were included in the first-parity analysis models. All effects were significant for metritis and retained placenta. For ketosis, all effects were significant, except for gestation length. For mastitis, only the effects of herd-year-season and calving age were significant. Variance components were computed by the multitrait animal model. The 4 diseases were analyzed jointly based on first-parity records, and each disease was analyzed separately for parities 1 to 3 with the different parities considered separate traits. The 4 disease traits in first parity were also analyzed jointly with the 6 major traits included in the Israeli breeding index: milk, fat, and protein production; somatic cell score; female fertility; and longevity. Heritability was highest for metritis and lowest for mastitis, but all heritabilities were <0.07, similar to previous studies. For all 4 diseases, genetic correlations among the first 3 parities were >0.65, and all residual correlations were <0.07. Selection of herd-years assumed to have more accurate recording of mastitis did not result in higher heritability estimates. Genetic correlations between the disease traits and milk, fat, and protein production were economically unfavorable, while correlations between the disease traits and somatic cell score, female fertility, and longevity were economically favorable. Expected genetic changes in the disease traits after 10 yr of selection with the current Israeli breeding index were all <1%, except for ketosis, which was predicted to increase by 1.5%. Inclusion of these traits in a proposed index with the disease traits constituting 7% of the index would result in only marginal improvements for the disease traits and adversely affect genetic gain for fat and protein production. Thus, inclusion of these traits in the breeding index cannot be justified economically.

Short communication: Selection for persistency by changing the shape of lactation curves with geometric morphometrics.

The objective was to simulate the response to selection by modifying the shape of the lactation curve to improve persistency in Israeli first-parity Holstein cattle using geometric morphometrics and multivariate quantitative genetics. The 2-dimensional Cartesian coordinates representing the shape of the lactation curve were characterized using geometric morphometrics. Genetic parameters of daily milk yield were estimated for the individual animal model using REML. Results of selection were simulated using the multivariate breeders' equation. We defined 6 selection regimens: (1) decrease in the third month in milk (MIM), (2) increase in the ninth MIM, (3) decrease in the third MIM and increase in the ninth MIM, (4) decrease in the first MIM, (5) decrease in the second MIM, and (6) decrease in the fourth MIM. The first 3 selection criteria targeted changes in the MIM of previous measurements of persistency in the Israeli Holstein population, and the last 3 targeted the months with the highest variability. All selection regimens attempted to modify the shape of the lactation curve while keeping total milk yield constant. The first 3 selection regimens showed greater total responses, with the highest response for decrease in the third MIM and increase in the ninth MIM. Magnitudes of correlated responses consistently surpassed direct responses in all selection criteria, suggesting that selection on specific parts of the lactation curve would produce correlated responses in other parts. Predicted responses to selections were depicted as shape changes from the mean shape in the data set. Most predicted responses demonstrated a fairly similar shape compared with the lactation curve. The predicted responses of lactation shapes of the last 3 selection regimens were overall lower in the first 3 MIM and decreased less in the last MIM, demonstrating a much flatter shape and thus improved persistency.

Using geometric morphometrics for the genetics analysis of shape and size of lactation curves in Israeli first-parity Holstein cattle.

Our objective was to combine the methods of geometric morphometrics and multivariate quantitative genetics to genetic evaluation of the size and shape of lactation curves of milk of 3,492 Israeli first-parity Holstein cattle. Lactation records were treated as morphological data, for which 2 different lactation shape functions were evaluated, one depicted by a line graph and the other by an orbital graph. The lactation curves from both shape functions were represented by 2-dimensional Cartesian landmark coordinates. The 2 sets of landmarks were then analyzed individually for each shape function with geometric morphometrics to separate variation into components of size and shape. The analysis yielded 2 size measures and 2 sets of shape variables, and they were the inputs to estimate variance components using the MTC REML individual animal model program. Variance components were also estimated for the 305-d lactation production as a reference. Shape variables showed negligible correlation with 305-d production, providing evidence of size and shape of lactation curve as separate characters. The size measure derived from the orbital-depicted lactation curve had equal heritability (0.39 ± 0.01; ± standard error) and complete genetic and environmental correlations with 305-d production, whereas the size measure derived from the line-depicted lactation curve showed low heritability (0.09 ± 0.01) and environmental correlation (0.02 ± 0.004) and relative high genetic correlation with 305-d production (0.48 ± 0.04). This may validate both the orbital graph to depict lactation records and the use of geometric morphometrics to split variation of lactation curve into size and shape components. The maximal heritability for shape of lactation curve was 0.55 for orbital- and 0.56 for line-depicted lactation curves. The respective patterns of variations were visualized as shape changes from the mean shape in the data set. Geometric morphometrics are well grounded within the theory of shape analysis and can be paired with conventional methods in the field to characterize the patterns of phenotypic and genetic variation of shape and size of lactation curve in dairy cattle.

Efficient inference of haplotypes from genotypes on a large animal pedigree.

We present a simple algorithm for reconstruction of haplotypes from a sample of multilocus genotypes. The algorithm is aimed specifically for analysis of very large pedigrees for small chromosomal segments, where recombination frequency within the chromosomal segment can be assumed to be zero. The algorithm was tested both on simulated pedigrees of 155 individuals in a family structure of three generations and on real data of 1149 animals from the Israeli Holstein dairy cattle population, including 406 bulls with genotypes, but no females with genotypes. The rate of haplotype resolution for the simulated data was >91% with a standard deviation of 2%. With 20% missing data, the rate of haplotype resolution was 67.5% with a standard deviation of 1.3%. In both cases all recovered haplotypes were correct. In the real data, allele origin was resolved for 22% of the heterozygous genotypes, even though 70% of the genotypes were missing. Haplotypes were resolved for 36% of the males. Computing time was insignificant for both data sets. Despite the intricacy of large-scale real pedigree genotypes, the proposed algorithm provides a practical rule-based solution for resolving haplotypes for small chromosomal segments in commercial animal populations.

Natural compounds derived from foods modulate nitric oxide production and oxidative status in epithelial lung cells.

The effects of natural antioxidants on nitric oxide (NO) modulation and oxidative status were determined in rat epithelial lung cells (L-2). Cells were stimulated with cytokines and treated with one of the following: resveratrol, soybean saponin group B (SSB), quercetin, genistein, olive leaf polyphenol concentrate (OLPC), or N-acetyl-L-cystein (NAC). NAC had no effect on NO levels, whereas resveratrol and OLPC were found to be effective in reducing nitrite levels, modifying iNOS mRNA, and decreasing free radical production. OLPC affected the levels of MnSOD while resveratrol did not, indicating that they act via different pathways. Quercetin and genistein reduced nitrite levels without affecting iNOS levels, presumably by scavenging NO. SSB did not affect nitrite levels, but exposure did reduce iNOS mRNA expression and protein levels, possibly due to antioxidant activity. Naturally occurring antioxidants, in particular resveratrol and OLPC, may have therapeutic potential in the treatment of inflammatory diseases.

Correcting for bias in estimation of quantitative trait loci effects.

Estimates of quantitative trait loci (QTL) effects derived from complete genome scans are biased, if no assumptions are made about the distribution of QTL effects. Bias should be reduced if estimates are derived by maximum likelihood, with the QTL effects sampled from a known distribution. The parameters of the distributions of QTL effects for nine economic traits in dairy cattle were estimated from a daughter design analysis of the Israeli Holstein population including 490 marker-by-sire contrasts. A separate gamma distribution was derived for each trait. Estimates for both the alpha and beta parameters and their SE decreased as a function of heritability. The maximum likelihood estimates derived for the individual QTL effects using the gamma distributions for each trait were regressed relative to the least squares estimates, but the regression factor decreased as a function of the least squares estimate. On simulated data, the mean of least squares estimates for effects with nominal 1% significance was more than twice the simulated values, while the mean of the maximum likelihood estimates was slightly lower than the mean of the simulated values. The coefficient of determination for the maximum likelihood estimates was five-fold the corresponding value for the least squares estimates.

An analytical formula to estimate confidence interval of QTL location with a saturated genetic map as a function of experimental design.

Analytical formulae are derived for the confidence interval for location of a quantitative trait locus (QTL) using a saturated genetic map, as a function of the experimental design, the QTL allele substitution effect, and the number of individuals genotyped and phenotyped. The formulae are derived assuming evenly spaced recombination events, rather than the actual unevenly spaced distribution. The formulae are useful for determining desired sample size when designing a wide variety of QTL mapping experiments, and for evaluating a priori the potential of a given mapping population for defining the location of a QTL. The formulae do not take into account the finite number of recombination events in a given sample.

Estimation of quantitative trait locus allele frequency via a modified granddaughter design.

A method is described on the basis of a modification of the granddaughter design to obtain estimates of quantitative trait loci (QTL) allele frequencies in dairy cattle populations and to determine QTL genotypes for both homozygous and heterozygous grandsires. The method is based on determining the QTL allele passed from grandsires to their maternal granddaughters using haplotypes consisting of several closely linked genetic markers. This method was applied to simulated data of 10 grandsire families, each with 500 granddaughters, and a QTL with a substitution effect of 0.4 phenotypic standard deviations and to actual data for a previously analyzed QTL in the center of chromosome 6, with substitution effect of 1 phenotypic standard deviation on protein percentage. In the simulated data the standard error for the estimated QTL substitution effect with four closely linked multiallelic markers was only 7% greater than the expected standard error with completely correct identification of QTL allele origin. The method estimated the population QTL allelic frequency as 0.64 +/- 0.07, compared to the simulated value of 0.7. In the actual data, the frequency of the allele that increases protein percentage was estimated as 0.63 +/- 0.06. In both data sets the hypothesis of equal allelic frequencies was rejected at P < 0.05.