@article{rocha_eisen_siewerdt_van vleck_pomp_2004, title={A large-sample QTL study in mice: III. Reproduction}, volume={15}, ISSN={["1432-1777"]}, DOI={10.1007/s00335-004-2364-6}, abstractNote={Using lines of mice having undergone long-term selection for high and low growth, a large-sample (n approximately to 1000 F2) experiment was conducted to gain further understanding of the genetic architecture of complex polygenic traits. Composite interval mapping on data from 10-week-old F2 females (n = 439) detected 15 quantitative trait loci (QTLs) on 5 chromosomes that influence reproduction traits characterized at day 16 of gestation. These QTL are broadly categorized into two groups: those where effects on the number of live fetuses (LF) were accompanied by parallel effects on the number of dead fetuses (DF), and those free of such undesirable effects. QTL for ovulation rate (OR) did not overlap with QTL for litter size, potentially indicating the importance of uterine capacity. Large dominance effects were identified for most QTL detected, and overdominance was also present. The QTL of largest effects were detected in regions of Chromosome 2, where large QTL effects for growth and fatness have also been found and where corroborating evidence from other studies exists. Considerable overlap between locations of QTL for reproductive traits and for growth traits corresponds well with the positive correlations usually observed among these sets of phenotypes. Some support for the relevance of QTL x genetic background interactions in reproduction was detected. Traits with low heritability demand considerably larger sample sizes to achieve effective power of QTL detection. This is unfortunate as traits with low heritability are among those that could most benefit from QTL-complemented breeding and selection strategies in food animal production.}, number={11}, journal={MAMMALIAN GENOME}, author={Rocha, JL and Eisen, EJ and Siewerdt, F and Van Vleck, LD and Pomp, D}, year={2004}, month={Nov}, pages={878–886} }
 @article{siewerdt_eisen_murray_2000, title={Correlated changes in fertility and fitness traits in lines of oMt1a-oGH transgenic mice selected for increased 8-week body weight}, volume={117}, ISSN={["0931-2668"]}, DOI={10.1111/j.1439-0388.2000x.00208.x}, abstractNote={Correlated responses in fitness and fertility traits were compared in transgenic and nontransgenic lines of mice selected for increased 8‐week body weight. Two replicates of lines which either carried or did not carry the sheep metallothionein‐1a sheep growth hormone transgene (oMt1a‐oGH) were established. Host lines had been previously selected for rapid growth or selected randomly. Within‐litter selection was carried out for 13 generations, and a randomly selected control line was kept for each set of replicate lines. Mice were genotyped every generation for the presence of the transgene, but this information was not used in selection decisions. The oMt1a‐oGH construct was activated by adding 25 mm ZnSO4 to the drinking water from 3 weeks (weaning) until 8 weeks of age. Zinc stimulation of the transgene was not carried out during mating, gestation and lactation. Correlated responses in fitness traits were measured by regression of least‐squares means (as deviations from the control lines) on generation number. Two fitness indexes were defined to combine the information on individual fitness traits. The proportion of infertile matings was higher in generations 7 to 13 than in generations 0 to 6. Correlated responses to selection showed an increase in the cohabitation to littering interval in nontransgenic lines and an increase in litter sizes in lines from the selected background. Preweaning pup survival did not change over generations. Overall fitness increased in the transgenic line from the selection background whereas no changes were observed in the transgenic line from the control background. The initial frequency of 0.5 of the transgene was reduced to less than 0.10 in the selected background, but increased to an average of 0.62 in the control lines. The comparison of specific mating groups involving transgenic and nontransgenic mates revealed that the only consistent disadvantage in having a transgenic parent was the increase in the length of the cohabitation to littering interval. Major fitness problems were not associated with the oMt1a‐oGH transgene, which makes this construct a potential choice for use in livestock breeding programmes.}, number={2}, journal={JOURNAL OF ANIMAL BREEDING AND GENETICS-ZEITSCHRIFT FUR TIERZUCHTUNG UND ZUCHTUNGSBIOLOGIE}, author={Siewerdt, F and Eisen, EJ and Murray, JD}, year={2000}, month={Apr}, pages={83–95} }
 @article{siewerdt_eisen_murray_parker_2000, title={Response to 13 generations of selection for increased 8-week body weight in lines of mice carrying a sheep growth hormone-based transgene}, volume={78}, DOI={10.2527/2000.784832x}, abstractNote={The purpose of this study was to evaluate selection in lines of transgenic mice. Two replicates of lines that either carried or did not carry the sheep metallothionein-1a sheep growth hormone transgene (oMt1a-oGH) were established. The host lines had been previously selected for rapid growth or selected randomly. Within-litter selection for increased 8-wk body weight was carried out for 13 generations. The frequency of oMt1a-oGH was monitored in all generations in the transgenic lines, but no genotypic information regarding the transgene was used as an aid to selection. The oMt1a-oGH was activated from weaning, at 3 wk, until 8 wk of age by adding ZnSO4 to the drinking water. Zinc stimulation of the transgene was not done during mating, gestation, or lactation. Data on body weights and weight gains were analyzed with a conventional mixed model and with an animal model. Genetic progress was achieved in all lines subjected to directional selection. In the control background, response to selection for 8-wk body weight was larger in the nontransgenic lines than in the transgenic lines, whereas no difference was found in the selected background. The frequency of the transgene was increased from the initial .5 to .62 in the randomly selected background but decreased to .04 in lines from a selected background. The REML estimates of variance components and genetic gain estimates varied greatly between the two methods. In general, there was better agreement between the realized heritability estimates and the heritability estimates obtained from the conventional mixed model analysis than between realized heritability estimates and results obtained using the animal model. Favorable correlated responses were obtained for 3- and 6-wk body weights and on 3- to 6- and 6- to 8-wk weight gains. Correlated responses to selection were larger in the selected than in the nonselected background but were not affected by the presence of the transgene. Results suggest that constructs similar to the oMt1a-oGH, which allow tight regulation, may be successfully incorporated into commercial livestock and should have larger effects in populations that have not been subject to selection.}, number={4}, journal={Journal of Animal Science}, author={Siewerdt, F. and Eisen, E. J. and Murray, J. D. and Parker, I. J.}, year={2000}, pages={832–845} }
 @inbook{siewerdt_eisen_murray_1999, title={Direct and correlated responses to short-term selection for 8-week body weight in lines of transgenic (oMt1a-oGH) mice}, booktitle={Transgenic animals in agriculture}, publisher={New York: CABI Publishing}, author={Siewerdt, F. and Eisen, E. J. and Murray, J. D.}, editor={J. D. Murray, G. B. Anderson and A. M. Oberbauer and McGloughlin, M. M.Editors}, year={1999} }
 @article{siewerdt_eisen_conrad-brink_murray_1998, title={Gene action of the oMt1a-oGH transgene in two lines of mice with distinct selection backgrounds}, volume={115}, ISSN={["0931-2668"]}, DOI={10.1111/j.1439-0388.1998.tb00344.x}, abstractNote={SummaryTen transgenic (sheep metallothionein 1a‐sheep growth hormone transgene, oMt1a‐oGH) homozygous male mice were mated to females of two lines with distinct selection backgrounds. Inter se matings yielded F2 mice in each line: selected background and control background. Genotypes with respect to the transgene insert were obtained in all mice. Weekly body weights were taken. Males were dissected at 8 weeks of age and fat pads and organs were weighed. Females were mated at 10 weeks; reproductive data were collected on the 16th day after detection of a copulatory plug. Gene action on body, fat pads and organs weights showed dominance effects. The oMt1a‐oGH transgene caused body and organ weights to increase and fat pad weights to reduce. No unfavourable effects of the transgene insert were found on reproductive traits. Results indicate that incorporation of the oMt1a‐oGH in populations of mice should be successful.}, number={3}, journal={JOURNAL OF ANIMAL BREEDING AND GENETICS-ZEITSCHRIFT FUR TIERZUCHTUNG UND ZUCHTUNGSBIOLOGIE}, author={Siewerdt, F and Eisen, EJ and Conrad-Brink, JS and Murray, JD}, year={1998}, month={Jun}, pages={211–226} }