J. Anim Sci.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J. Anim Sci. 2008. 86:2862-2871. doi:10.2527/jas.2008-1083
© 2008 American Society of Animal Science
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jas.2008-1083v1
86/11/2862    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lancaster, P. A.
Right arrow Articles by Welsh, T. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lancaster, P. A.
Right arrow Articles by Welsh, T. H., Jr.

ANIMAL GENETICS

Effects of divergent selection for serum insulin-like growth factor-I concentration on performance, feed efficiency, and ultrasound measures of carcass composition traits in Angus bulls and heifers

P. A. Lancaster*, G. E. Carstens*,1, F. R. B. Ribeiro*, M. E. Davis{dagger}, J. G. Lyons* and T. H. Welsh, Jr.*

* Department of Animal Science, Texas A&M University, College Station 77843; and {dagger} Department of Animal Sciences, The Ohio State University, Columbus 43210


   Abstract
Top
 Abstract
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 LITERATURE CITED
 
Angus bulls and heifers from lines divergently selected for serum IGF-I concentration were used to evaluate the effects of IGF-I selection line on growth performance and feed efficiency in 2 studies. In study 1, bulls (low line, n = 9; high line, n = 8; initial BW = 367.1 ± 22.9 kg) and heifers (low line, n = 9; high line, n = 13; initial BW = 286.4 ± 28.6 kg) were adapted to a roughage-based diet (ME = 1.95 Mcal/kg of DM) for 24 d and fed individually for 77 d by using Calan gate feeders. In study 2, bulls (low line, n = 15; high line, n = 12; initial BW = 297.5 ± 34.4 kg) and heifers (low line, n = 9; high line, n = 20; initial BW = 256.0 ± 25.1 kg) were adapted to a grain-based diet (ME = 2.85 Mcal/kg of DM) for 32 d and fed individually for 70 d by using Calan gate feeders. Blood samples were collected at weaning and at the start and end of each study, and serum IGF-I concentration was determined. Residual feed intake (RFI) was calculated, within study, as the residual from the linear regression of DMI on midtest BW0.75, ADG, sex, sex by midtest BW0.75 and sex by ADG. In study 1, calves from the low IGF-I selection line had similar initial and final BW and ADG, compared with calves from the high IGF-I selection line. In addition, DMI and feed conversion ratio were similar between IGF-I selection lines; however, calves from the low IGF-I selection line tended (P < 0.10) to have lesser RFI than calves from the high IGF-I selection line (–0.26 vs. 0.24 ± 0.31 kg/d). In study 2, IGF-I selection line had no influence on performance or feed efficiency traits. However, there was a tendency (P = 0.15) for an IGF-I selection line x sex interaction for RFI. Bulls from the low IGF-I selection line had numerically lesser RFI than those from the high IGF-I selection line, whereas in heifers, the IGF-I selection line had no effect on RFI. In studies 1 and 2, weaning and initial IGF-I concentrations were not correlated with either feed conversion ratio or RFI. However, regression analysis revealed a sex x IGF-I concentration interaction for initial IGF-I concentration in study 1 and weaning IGF-I concentration in study 2 such that the regression coefficient was positive for bulls and negative for heifers. These data suggest that genetic selection for postweaning serum IGF-I concentration had a minimal effect on RFI in beef cattle.

Key Words: beef cattle • carcass composition • divergent selection • insulin-like growth factor-I • residual feed intake


   INTRODUCTION
Top
 Abstract
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 LITERATURE CITED
 
Feed efficiency is an important trait to consider in developing selection programs to identify cattle that are more economically and environmentally sustainable to produce. Considerable genetic variation is known to exist in efficiency of feed utilization (Herd and Bishop, 2000Go), but the expense of measuring feed intake in cattle has limited the implementation of selection programs that target this trait. Moreover, the traditional measure of feed efficiency (feed conversion ratio; FCR) is inversely related to growth and mature size, such that selection for improved FCR leads to larger mature cow size (Archer et al., 1999Go). Residual feed intake (RFI) is an alternative measure of efficiency that facilitates selection for improved feed efficiency in cattle independent of growth traits and mature size.

Identification of physiological indicators that are predictive of RFI would facilitate early detection, and enhance accuracy of selection of animals with improved feed efficiency. The endocrine actions of IGF-I affect glucose and AA metabolism, protein accretion, and linear growth (Jones and Clemmons, 1995Go), suggesting a role for IGF-I in nutrient utilization. Research from Australia has demonstrated that serum concentrations of IGF-I are genetically correlated with RFI in pigs (Bunter et al., 2002Go) and cattle (Moore et al., 2005Go). Specifically, Moore et al. (2005)Go reported a strong genetic correlation (0.57) between RFI and serum IGF-I in bulls and heifers. Likewise, Brown et al. (2004)Go reported positive phenotypic correlations of serum IGF-I with RFI (0.38) and FCR (0.36) in growing bulls.

Since 1989, Davis and coworkers have conducted a divergent selection study based on postweaning serum IGF-I concentrations in Angus cattle. After 5 yr of selection, Davis and Simmen (1997)Go reported a negative genetic correlation (–0.30 to –0.50) between serum IGF-I concentration and postweaning BW gain. However, a more recent analysis (Davis and Simmen, 2006Go) revealed that IGF-I was positively correlated (0.10 to 0.30) with growth traits after 10 yr of divergent selection. These researchers have not evaluated feed efficiency traits in calves selected for low or high serum IGF-I concentration. Therefore, the primary objective of this study was to examine the effects of divergent selection for serum IGF-I on performance and feed efficiency traits in Angus calves. The central hypothesis tested was that calves from the low IGF-I selection line would have improved RFI compared with calves from the high IGF-I selection line.


   MATERIALS AND METHODS
Top
 Abstract
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 LITERATURE CITED
 
Animals and Management

Before the start of this study, all procedures were approved by the Institutional Animal Care and Use Committee of The Ohio State University and Texas A&M University.

Angus bull and heifer progeny from parents divergently selected for serum IGF-I concentration for approximately 13 yr at the Eastern Agricultural Research Station (EARS, The Ohio State University) were used in this study. Selection procedures are reported elsewhere (Davis et al., 1995Go). Briefly, each year the calves with the greatest (n = 4 bulls and 8 heifers) and least (n = 4 bulls and 8 heifers) residuals for IGF-I concentrations (adjusted for age of calf and age of dam) were used for subsequent breeding seasons for the respective selection lines. Selection was based on the average of 3 IGF-I serum samples taken at d 28, 42, and 56 of the 140-d postweaning performance test. The selected bulls and heifers were confirmed "satisfactory" based on a posttest breeding soundness exam or confirmed pregnant, respectively. All heifers were bred and selections were made from those confirmed pregnant. Eight cows from each respective line based on physical unsoundness, failure to conceive, and old age were replaced by the selected heifers. Heifers within the high IGF-I selection line were stratified such that 1 of the 4 heifers with the greatest IGF-I concentration, 1 of the 4 heifers with the next-greatest IGF-I concentration, and so on, was assigned to each of the 4 bulls from the high IGF-I selection line for mating. This mating procedure was duplicated for the low IGF-I selection line.

Calves used in this experiment were weaned on October 6, 2004, and October 5, 2005, and shipped to the O. D. Butler Jr. Animal Science Complex at Texas A&M University on February 10, 2005, and January 11, 2006, for studies 1 and 2, respectively. In study 1, on weaning, calves were adapted to a grain-based diet (30% shelled corn, 25% crimped oats, 10% ground corn-cobs, 10% dehydrated alfalfa, 10% wheat middlings, 10% soybean meal, 3% molasses, and 2% minerals, on an as-fed basis) at the EARS for 55 d, and growth traits were measured for 70 d; bulls were allowed ad libitum access to the diet, whereas heifers were limit fed to gain approximately 0.75 kg/d. On arrival at Texas A&M University, bulls (low line, n = 9; high line, n = 8; initial age = 352 ± 10.3 d; and BW = 367.1 ± 22.9 kg) and heifers (low line, n = 9; high line, n = 13; initial age = 359 ± 5.5 d; and BW = 286.4 ± 28.6 kg) were blocked by sex and BW, randomly assigned to pens (2 pens of 6 bulls and 1 pen of 5 bulls; 3 pens of 6 heifers and 1 pen of 4 heifers), and adapted to a roughage-based diet (ME = 1.95 Mcal/kg of DM) for 24 d. In study 2, on weaning calves were fed fescue hay ad libitum and offered a supplement (80% soybean hulls:20% shelled corn) at 2.7 kg·head–1·d–1 for 98 d before being shipped to Texas A&M University. On arrival, bulls (low line, n = 15; high line, n = 12; initial age = 324 ± 10.6 d; and BW = 297.5 ± 34.4 kg) and heifers (low line, n = 9; high line, n = 20; initial age = 326 ± 9.7 d; and BW = 256.0 ± 25.1 kg) were blocked by sex and BW, randomly assigned to pens (4 pens of 6 bulls and 1 pen of 3 bulls; 4 pens of 6 heifers and 1 pen of 5 heifers), and adapted to a grain-based diet (ME = 2.85 Mcal/kg of DM) for 32 d. Individual intakes were measured by using Calan gate feeders (American Calan, Northwood, NH) for 77 and 70 d in studies 1 and 2, respectively.

Diet ingredient samples were collected weekly throughout each study and composited by weight for chemical analyses. Moisture analysis was conducted by drying in a forced-air oven for 48 h at 105°C (AOAC, 1995Go). Chemical analysis was conducted by an independent laboratory (Cumberland Valley Analytical Services Inc., Hagerstown, MD), and ME concentrations of the experimental diets were computed by using the Cornell Net Carbohydrate and Protein System (version 5.0, Cornell University, Ithaca, NY). Ingredient and chemical composition of the experimental diets are presented in Table 1Go. Moisture analysis of diet ingredient samples was used to determine average daily DMI from as-fed feed intake data.


View this table:
[in this window]
[in a new window]

  		Table 1. Ingredient and chemical composition of diets fed to bulls and heifers in studies 1 and 2
 
Growth, Ultrasound, and IGF-I Measurements

Body weights were measured at 7-d intervals and growth rates of individual calves were modeled by linear regression of BW against day of study by using the general linear model (SAS Inst. Inc., Cary, NC). Regression coefficients were used to compute initial and final BW, ADG, and metabolic BW (MBW; midtest BW0.75). Ultrasound measures of 12th-rib backfat thickness (BF) and LM area (LMA) were obtained at the start and end of each study by a Ultrasound Guidelines Council field-certified technician using an Aloka 500-V instrument with a 17-cm 3.5-MHz transducer (Corometrics Medical Systems Inc., Wallingford, CT). Images were analyzed by using Beef Image Analysis Pro software (Designer Genes Inc., Harrison, AR) in study 1 and were sent to the National Centralized Ultrasound Processing Laboratory (Ames, IA) for analysis in study 2. In addition, hip height was measured at the start and end of each study.

To determine serum IGF-I concentrations at weaning, blood samples were collected via jugular venipuncture onto blood spot cards at 2 wk postweaning in study 1 and at weaning in study 2. The IGF-I analysis was conducted by Primegro Limited (Adelaide, Australia) using a commercially available ELISA assay (Diagnostic Systems Laboratories Inc., Webster, TX). The reported intraassay CV was <10%, and sensitivity for minimum detection was 0.01 ng/mL. At the start and end of each feed intake measurement period, blood samples were collected via jugular venipuncture using (10 mL) evacuated serum tubes (Becton, Dickinson and Company, Franklin Lakes, NJ), and serum was harvested by centrifugation (3,000 x g at 4°C for 20 min) after blood samples were allowed to clot overnight at 4°C. Serum samples were stored at –20°C for later analysis of IGF-I concentrations in duplicate by using enzyme immunoassay procedures (IDS Inc., Fountain Hills, AZ). The sensitivity of the assay was 3.1 ng/mL and intra- and interassay CV were 5.3 and 5.9%, respectively.

Calculations and Statistical Analysis

Preliminary analysis of RFI revealed significant effects of sex and sex x MBW and ADG interaction terms in study 2, but not in study 1. In addition, previous research (Crews et al., 2003Go) has demonstrated that although the genetic correlation (rg = 0.55) between RFI measured on roughage- versus grain-based diets is strong, these 2 RFI traits may not be biologically equivalent. Therefore, RFI was calculated separately within each study, and the fixed effect of sex and the interaction terms were included in the model to compute RFI for both studies. Residual feed intake was computed as the difference between actual DMI and that predicted from the regression of DMI on MBW and ADG by using the following model:


Formula

where β0 is the y-intercept, β1 is the partial regression coefficient of MBW, β2 is the partial regression coefficient of ADG, β3 is the partial regression coefficient of sex, β4 is the partial regression coefficient of the sex x MBW interaction, β5 is the partial regression coefficient of the sex x ADG interaction, and {euro} is the error term.

Data from each study were analyzed separately. The effects of IGF-I selection line and sex on performance, feed efficiency, and ultrasound measures of carcass composition traits were evaluated by using the GLM procedure of SAS. The model included fixed effects of IGF-I selection line, sex, and the interaction term. Least squares means were computed for the IGF-I selection line within sex groups, and pairwise comparisons were made by using Tukey’s W procedure. Phenotypic correlations among performance, feed efficiency, and ultrasound measures of carcass composition traits and serum IGF-I concentrations were computed by using the PROC CORR of SAS with the partial option used to adjust for the fixed effects of sex and IGF-I selection line. Additionally, regression analysis was used to evaluate the effect of sex on the relationship between RFI and serum IGF-I. The full model included the effects of sex, selection line, and sex x selection line interaction as class variables, serum IGF-I concentration as a covariate, and all interactions. Nonsignificant interaction terms were removed, and the final reduced model included sex, selection line, serum IGF-I, and the sex x serum IGF-I interaction.


   RESULTS
Top
 Abstract
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 LITERATURE CITED
 
The regression model to compute RFI explained 64 and 71% of the variation in DMI in study 1 and 2, respectively. The means ± SD for RFI were 0.00 ± 0.91 and 0.00 ± 0.90 kg/d for bulls and heifers, respectively, in study 1, and 0.00 ± 0.77 and 0.00 ± 0.61 kg/d for bulls and heifers, respectively, in study 2. The SD of RFI in study 1 were within the range (0.74 to 1.47 kg/d) previously reported for cattle fed roughage diets (Arthur et al., 2001bGo,cGo; Carstens et al. 2002Go; Schenkel et al., 2004Go). Similarly, the SD of RFI in study 2 was within the range (0.66 to 0.83 kg/d) reported for cattle fed a grain diet (Basarab et al., 2003Go; Nkrumah et al., 2004Go). These results indicate that the variation in RFI in our studies using calves divergently selected for serum IGF-I concentration was similar to previously reported studies using traditional contemporary groups.

As expected, serum concentrations of IGF-I were affected by selection line (Table 2Go). At weaning, calves from the high IGF-I selection line had 31 and 40% greater (P < 0.05) IGF-I concentrations than calves from the low selection line in studies 1 and 2, respectively. There was a sex x selection line interaction (P < 0.05) effect on IGF-I concentration at the start of study 1. High selection line bulls had 36% greater (P < 0.05) IGF-I concentrations than low selection line bulls, whereas heifers from the divergent selection lines had similar serum IGF-I concentrations at the start of study 1. At the end of study 1, and at the start and end of study 2, IGF-I concentrations were 16 to 23% greater (P < 0.05) in calves from the high selection line compared with those from the low selection line.


View this table:
[in this window]
[in a new window]

  		Table 2. Effects of sex and IGF-I selection line on serum IGF-I concentration in studies 1 and 2
 
In study 1, IGF-I selection line had little influence on ultrasound measurements of carcass composition (Table 3Go). In study 2, calves from the high IGF-I selection line had greater (P = 0.02) final BF (0.74 vs. 0.63 ± 0.06 cm; IGF-I selection line main effect means ± largest SEM) and gain in BF (0.37 vs. 0.27 ± 0.05 cm) than calves from the low IGF-I selection line. Final LMA and gain in LMA were similar between IGF-I selection lines in study 2.


View this table:
[in this window]
[in a new window]

  		Table 3. Effects of sex and IGF-I selection line on ultrasound measures of composition traits in studies 1 and 2
 
In study 1, calves from the low IGF-I selection line had similar initial and final BW, ADG, and final hip height compared with calves from the high IGF-I selection line (Table 4Go). Although IGF-I selection lines had similar FCR and DMI, calves from the low IGF-I selection line tended (P = 0.09) to have lesser RFI (–0.26 vs. 0.24 kg/d) than calves from the high IGF-I selection line. In study 2, IGF-I selection line had no effect on growth traits, DMI, FCR, or RFI. However, there was a tendency (P = 0.15) for an IGF-I selection line x sex interaction for RFI. Bulls from the low IGF-I selection line had numerically lesser RFI compared with bulls from the high IGF-I selection line, whereas RFI was similar between IGF-I selection lines in heifers. Even though a numeric trend was observed for RFI, a statistical difference between IGF-I selection lines could not be detected. The lack of a statistical difference was likely due to the small number of animals in both studies. Given the reported variance for RFI, 47 animals per IGF-I selection line would have been necessary to detect a significant difference ({alpha} = 0.05; β ≤ 0.10) between IGF-I selection lines in study 1, assuming no sex x selection line interaction.


View this table:
[in this window]
[in a new window]

  		Table 4. Effects of sex and IGF-I selection line on performance and feed efficiency traits in studies 1 and 2
 
For bulls in studies 1 and 2, the average RFI was –0.24 vs. 0.27 kg/d for the low and high selection lines, respectively. Assuming a heritability for RFI of 0.39 (Arthur et al., 2001aGo) and a mean RFI of 0.00 for breeding females, a feedlot with 10,000 cattle on feed for an average of 120 d would use 119,000 kg less feed if bulls from the low IGF-I selection line were used to sire the offspring compared with bulls from the high IGF-I selection line. Assuming a ration cost of $180 per ton, this would translate into $23,500 in feed cost savings for the same final BW and ADG. Thus, the consistent numeric differences in RFI of bulls in both studies, even though not statistically significant, have a large biological significance.

Phenotypic correlations among serum IGF-I concentrations at the various sampling times are presented in Table 5Go. Weaning IGF-I concentrations were not correlated with either initial or final IGF-I concentration, but initial IGF-I concentration was positively correlated with final IGF-I concentration (0.44 and 0.25 in study 1 and 2, respectively). The lack of correlation of weaning with initial or final IGF-I concentration may be due to different procedures for determining serum IGF-I concentration; weaning samples were collected by using a blood spot card and analyzed by using an ELISA by Primegro Inc., whereas initial and final blood samples were collected in evacuated serum vials and harvested serum was analyzed by using an enzyme immunoassay procedure in our laboratory.


View this table:
[in this window]
[in a new window]

  		Table 5. Phenotypic partial correlations between performance, feed efficiency, and ultrasound measurements of composition traits for bulls and heifers in studies 1 (above the diagonal) and 2 (below the diagonal)
 
In studies 1 and 2, DMI was strongly correlated with ADG and final BW (0.73 and 0.70 for study 1 and 2, respectively). As expected, RFI was strongly correlated with DMI, but not with ADG or final BW in either study. In contrast, FCR was negatively correlated with ADG in both studies, and positively correlated with DMI in study 2, but not in study 1. In both studies, RFI was strongly correlated with FCR. Gain in BF during studies 1 and 2 was moderately correlated with both ADG (0.37 and 0.40, respectively) and DMI (0.47 and 0.38, respectively). In both studies, gain in LMA was moderately correlated with ADG (0.40 and 0.41 for study 1 and 2, respectively), but was not correlated with DMI. Ultrasound measurements of carcass composition traits were not correlated with FCR or RFI in either study.

In study 1, serum IGF-I concentration was not correlated with ADG, DMI, or gain in BF at any of the blood sampling times, although IGF-I concentration sampled at the end of the study was positively correlated with gain in LMA. In study 2, serum IGF-I concentration was not correlated with ADG at any of the sampling times, but IGF-I concentration sampled at weaning and at the start of the study were positively correlated with DMI. Serum IGF-I concentration was not correlated with gain in BF or LMA at any sampling time.

In study 1, weaning and initial IGF-I concentrations were not correlated with FCR or RFI, but final IGF-I concentration was negatively correlated with both FCR (–0.49) and RFI (–0.40). Regression analysis revealed that sex influenced the relationship between initial serum IGF-I concentration and RFI (Table 6Go). The regression coefficient tended (P = 0.15) to be greater than zero for bulls, and less than zero for heifers (5.38 vs. –9.49 g/d, respectively). In study 2, serum IGF-I concentration was not correlated with FCR or RFI at any of the sampling times. However, there was a significant sex x weaning IGF-I concentration interaction. The regression coefficient between weaning IGF-I concentration and RFI was greater (P < 0.05) than zero for bulls, but was not different from zero for heifers (5.16 vs. –3.41 g/d, respectively).


View this table:
[in this window]
[in a new window]

  		Table 6. Regression coefficient estimates (±SE) for regression of RFI (g/d) on serum IGF-I and sex by serum IGF-I interaction in studies 1 and 2
 
The relationship between RFI and serum IGF-I concentration appeared to be affected by the age at the time of blood sampling for IGF-I. For heifers in study 1, the regression coefficients relating RFI to serum IGF-I concentration became more negative as age at time of blood sampling increased. The regression coefficient for IGF-I sampled at weaning was not significantly different from zero, whereas the regression coefficients for IGF-I sampled at the start (P = 0.15) and end (P < 0.05) of the study were less than zero (–1.14, –9.49, and –10.87 g/d, respectively). For bulls in study 2, the regression coefficients for IGF-I became less positive as age at time of blood sampling increased. The coefficients for IGF-I were greater than zero when sampled at weaning (P < 0.05) and the start (P = 0.11) of the study, but were not different from zero when sampled at the end of the study (5.16, 4.33, and 1.18 g/d, respectively). Similar trends for the relationship between RFI and serum IGF-I concentrations were not observed for heifers in study 2 or bulls in study 1.

Bulls had 30 and 48% greater (P < 0.05) IGF-I concentrations at weaning than heifers in studies 1 and 2, respectively (Table 2Go). Furthermore, bulls had 70 to 100% greater (P < 0.05) IGF-I concentrations at the start and end of studies 1 and 2 than heifers. As expected, bulls were heavier (P < 0.05) at the start and end of the study, and had greater (P < 0.05) ADG than heifers in both studies (Table 3Go). Likewise, bulls had improved (P < 0.05) FCR compared with heifers in study 1 (9.12 vs. 11.77 ± 0.47 DMI:gain) and study 2 (5.79 vs. 7.09 ± 0.26 DMI:gain). As expected, RFI was not affected by sex because sex was included in the model used to compute RFI.

Bulls in study 1 had greater (P < 0.05) LMA at the start (62.1 vs. 48.1 ± 2.11 cm2) and end (74.61 vs. 65.72 ± 2.53 cm2) of the study, but they gained (P < 0.05) less LMA during the study than heifers. However, bulls in study 1 gained (P < 0.05) less BF (0.18 vs. 0.53 ± 0.05 cm) during the study then heifers. As expected, bulls in study 2 gained (P < 0.01) more LMA (25.25 vs. 18.52 ± 1.81 cm2) and gained (P < 0.01) less BF (0.26 vs. 0.37 ± 0.05 cm) during the study compared with heifers. The lesser gain in LMA for bulls than heifers during study 1 was likely because heifers were limit fed, whereas bulls were fed ad libitum a high-grain diet for 125 d at the EARS station before the beginning of the study. In study 2, the previous plane of nutrition was similar for both bulls and heifers.


   DISCUSSION
Top
 Abstract
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
LITERATURE CITED
 
Residual feed intake is an alternative feed efficiency trait that has received considerable attention in recent years. Several review papers (Arthur et al., 2004Go; Herd et al., 2004Go; Richardson and Herd, 2004Go) have emphasized the potential use of RFI as a measure of feed efficiency in selection programs to improve feed utilization and the economics of beef production. However, adoption of feed efficiency technology by the beef industry is hindered by the high cost of measuring feed intake. Thus, biological markers that could assist in the identification of superior animals would be beneficial. Insulin-like growth factor-I is a hormone involved in growth and nutrient utilization by body tissues. Biological differences in the GH–IGF-I axis could be important factors influencing the variation in feed utilization by beef cattle. Understanding the relationships between serum IGF-I concentration and performance and feed efficiency traits is important to developing selection programs that incorporate IGF-I as a biological marker. This study found that 13 and 14 yr of divergent selection for postweaning serum IGF-I concentration resulted in similar growth, feed intake, and feed efficiency in Angus bulls and heifers. However, the relationship between serum IGF-I concentration and RFI was different between bulls and heifers.

IGF-I and Feed Efficiency

Previous studies have reported positive genetic correlations between postweaning IGF-I concentration and RFI in Bos taurus cattle fed roughage diets (Johnston et al., 2002Go, rg = 0.39; Moore et al., 2005Go, rg = 0.57). In these studies, RFI was measured postweaning at approximately 9 to 11 mo of age. Results from these studies led to the use of serum IGF-I as an indicator trait for genetic evaluation of RFI in Angus bulls by the Australian Angus Association (http://www.angusaustralia.com.au). The numerically lesser (P < 0.10) RFI for bulls from the low IGF-I selection line compared with bulls from the high IGF-I selection line in studies 1 and 2 supports the positive genetic correlations reported in these studies. However, Wolcott et al. (2006)Go reported negative genetic correlations between postweaning IGF-I concentration and RFI in Brahman (–0.12) and nonadapted tropical composite steers (–0.80). In the later study, RFI was measured in yearling steers (initial BW = 400 kg) fed a high-grain diet and implanted with Compudose (VetLife, Des Moines, IA). In our study, weaning and initial IGF-I concentrations were not correlated with RFI in either study 1 (roughage fed) or study 2 (grain fed). However, regression analysis revealed a sex x serum IGF-I concentration interaction for initial IGF-I concentration for study 1, and for weaning IGF-I concentration in study 2 such that relationships between IGF-I concentration and RFI were positive for bulls and negative for heifers. No previous studies have evaluated the relationship between IGF-I concentration and RFI in bulls compared with heifers, but the conflicting results between bulls vs. heifers may be related to differences in composition of gain.

Using prediction equations derived from carcass traits for bulls (Baker et al., 2006aGo) and heifers (Baker et al., 2006bGo), growth of empty-body fat was estimated from ultrasound measurements. As expected, bulls had a greater proportion of empty BW gain as fat-free empty BW compared with heifers in study 1 (76.0 vs. 68.6%) and study 2 (83.0 vs. 71.7%). This difference between bulls and heifers corresponded to the positive relationships for bulls and negative relationships for heifers between IGF-I concentration and RFI and the numerically greater difference in RFI between IGF-I selection lines in bulls compared with heifers. These data suggest that the relationship between serum IGF-I concentration and RFI may be more positive when RFI is measured in cattle that are experiencing greater lean tissue growth. Similarly, the Animal Genetics and Breeding Unit (2007)Go and Brown (2005)Go reported positive genetic and phenotypic correlations, respectively, in cattle fed a roughage-based diet (0.17 and 0.18, respectively) and negative genetic and phenotypic correlations, respectively, in cattle fed a grain-based diet (–0.22 and –0.12, respectively), where cattle would be expected to have a greater rate of lean tissue gain when younger and fed a roughage-based diet before a finishing phase. Arguably, rate of lean tissue gain may have influenced the positive relationships between IGF-I concentration and RFI observed by Moore et al. (2005)Go compared with the negative relationships observed by Wolcott et al. (2006)Go. In the study by Moore et al. (2005)Go, cattle were fed a roughage-based diet at 9 to 11 mo of age, whereas in the study by Wolcott et al. (2006)Go, cattle were fed a grain-based diet after a growing phase to reach an initial BW of 400 kg, indicating that these cattle were most likely much older and closer to maturity, and most likely had a lesser proportion of lean gain. These studies may indicate that diet type affected the relationship between serum IGF-I concentration and RFI; however, in our studies, bulls had positive relationships compared with negative relationships for heifers when fed a roughage-based diet in study 1 or a grain-based diet in study 2. Given the known biological actions of IGF-I to increase protein synthesis and accretion (Jones and Clemmons, 1995Go), the effect of lean tissue growth rate during the RFI measurement period on the relationship between IGF-I concentration and RFI seems plausible.

In study 1, the difference in RFI between IGF-I selection lines was less than expected based on previously reported genetic correlations (Johnston et al., 2002Go, rg = 0.39; Moore et al., 2005Go, rg = 0.57) and the number of years that selection pressure had been applied to serum IGF-I by Davis and coworkers. The concept that the relationship between serum IGF-I concentration and RFI may be stronger when RFI is measured in animals with a high rate of lean tissue growth would explain the small differences in our study. In our study, bulls and heifers were measured for RFI at 12 mo (356 ± 8.5 d) of age after a previous performance trial using a grain-based diet, whereas Johnston et al. (2002)Go and Moore et al. (2005)Go measured RFI in weaned calves at 9 to 11 mo of age, which suggests differences in rate of lean tissue growth between those studies and this study. Thus, the fact that bulls and heifers were measured for RFI at a later stage of maturity most likely influenced the differences between IGF-I selection lines and our ability to detect a significant difference between IGF-I selection lines in study 1.

Moore et al. (2005)Go reported that IGF-I sampled at weaning and postweaning were the same trait (rg = 1.0). Similarly, Davis and Simmen (2006)Go reported strong genetic correlations between serum IGF-I concentrations sampled 14 (0.87) or 28 d apart (0.89). However, age at sampling for IGF-I concentration appeared to affect the relationship between serum IGF-I concentration and RFI in both of our studies. For heifers in study 1, the regression coefficient became increasingly negative as IGF-I was sampled at a later age. In study 2, the regression coefficient for bulls became less positive as IGF-I was sampled at a later age. Brown (2005)Go also reported that the relationship between serum IGF-I concentration and RFI became less positive as IGF-I concentration was measured later in the growing period (rp = 0.18 and 0.04 for initial and final IGF-I concentration, respectively) and more negative as IGF-I concentration was measured later in the finishing period (rp = –0.12 and –0.18 for initial and final IGF-I concentration, respectively) for Santa Gertrudis steers. Wolcott et al. (2006)Go reported that the relationship between IGF-I concentration and RFI became increasingly negative as IGF-I was sampled later in the finishing period for Brahman steers (rg = –0.12, 0.03, and –0.54 for postweaning, initial, and final IGF-I concentration, respectively), but became less negative for tropical composite steers (–0.80, –0.51, and -0.44 for postweaning, initial, and final IGF-I concentration, respectively). Collectively, these data suggest that as cattle become more physiologically mature, the relationship between IGF-I concentration and RFI becomes increasingly negative both in terms of sampling IGF-I and measuring RFI.

IGF-I and Growth

Previous studies evaluating the relationship between serum IGF-I concentration and growth traits have reported conflicting results. Lund-Larsen et al. (1977)Go measured IGF-I concentration at 5, 7, and 10 mo of age in growing bulls and reported that the mean serum IGF-I concentration was phenotypically positively correlated with ADG. Bishop et al. (1989)Go measured IGF-I concentration at 28-d intervals during a 140-d postweaning test and found that phenotypic correlations between IGF-I concentration and final BW (–0.17 to 0.38) and ADG (–0.23 to 0.21) varied by day of sampling. In a more recent study, Moore et al. (2005)Go reported negative genetic correlations between weaning serum IGF-I concentration measured by using Primegro Inc. blood-spot cards and 200-d (–0.22) and 400-d adjusted BW (–0.28) in Angus bulls and heifers. Furthermore, Johnston et al. (2002)Go reported a negative genetic correlation between postweaning IGF-I concentration and ADG (–0.20) in Angus cattle. In studies using growing pigs, Luxford et al. (1998)Go and Suzuki et al. (2004)Go reported genetic correlations of –0.47 and 0.26, respectively, between IGF-I concentration and ADG. After 7 generations of divergent selection for plasma IGF-I concentration in mice, Blair et al. (1988)Go found that mice selected for increased plasma IGF-I concentration had greater BW at 6 and 20 wk of age than mice selected for low plasma IGF-I concentration. After 3 yr of divergent selection for postweaning serum IGF-I concentration in Angus bulls and heifers, Pagan et al. (2003)Go reported similar IGF-I concentrations, final BW and postweaning ADG between selection lines. After 5 yr of divergent selection, Davis and Simmen (1997)Go reported negative genetic correlations of serum IGF-I concentration with final BW (–0.31) and ADG (–0.40). However, after 10 yr of divergent selection for IGF-I concentration, the genetic correlations between serum IGF-I concentration and ADG and final BW were positive (0.28 and 0.29; Davis and Simmen, 2006Go), and bulls and heifers from the high IGF-I selection line had 65% greater serum IGF-I concentration and 4% greater final BW than those from the low IGF-I selection line (Pagan et al., 2003Go). In study 1, there was a tendency (P = 0.06) for bulls and heifers from the low IGF-I selection line to have greater final BW, but there was no effect of IGF-I selection line on final BW in study 2. In addition, there was no effect of IGF-I selection line on ADG and no correlation between serum IGF-I concentration and ADG in either study. These data suggest that other factors may be influencing the relationship of IGF-I concentration with growth and body size.

IGF-I and Carcass Composition

Insulin-like growth factor-I is known to stimulate protein synthesis and satellite cell proliferation in skeletal muscle (Oksbjerg et al., 2004Go), suggesting that a positive association between serum IGF-I concentration and lean tissue growth may exist. Anderson et al. (1988)Go assessed IGF-I concentration every 30 min from 0800 to 2000 h on d –1, 65, 135, and 201 of a 202-d test in growing bulls. These authors reported that mean serum IGF-I concentration was negatively correlated with percentage of carcass fat (r2 = –0.60) and fat thickness (r2 = –0.73), but was positively correlated with percentage of carcass protein (r2 = 0.60). In contrast, Moore et al. (2005)Go sampled IGF-I concentration at 310 d of age in growing cattle and reported a positive genetic correlation with ultrasound BF (0.29) and a negative genetic correlation with ultrasound LMA (–0.37). Furthermore, Johnston et al. (2001)Go and Luxford et al. (1998)Go found positive genetic correlations between serum IGF-I concentration and measures of fat thickness in cattle (0.38) and pigs (0.29), respectively. After 8 yr of divergent selection for postweaning serum IGF-I concentration, Davis and Simmen (2000)Go reported a negative genetic correlation between serum IGF-I concentration and carcass backfat thickness (–0.28), but a positive genetic correlation with LMA (0.17). However, after 10 yr of divergent selection for IGF-I concentration, the genetic correlations between IGF-I concentration and ultrasound BF thickness and LMA were 0.19 and 0.20, respectively (Davis et al., 2003Go). In study 1, there was no effect of IGF-I selection on ultrasound measurements of composition traits, but in study 2, bulls and heifers from the low IGF-I selection line had less final BF and gained less BF during the study. Weaning and initial IGF-I concentrations were not correlated with gain in BF or LMA in either study, but final IGF-I concentration was positively correlated with gain in LMA (0.45) in study 1.

These results demonstrate inconsistent relationships between serum IGF-I concentration and growth, carcass composition, and feed efficiency traits. Insulin-like growth factor-I binding proteins, proteins associated with circulating IGF-I, modulate the interaction of IGF-I with its receptor (Jones and Clemmons, 1995Go). Previous research has reported that IGFBP-2 was negatively related to BW (Pagan et al., 2003Go) and positively related to ADG (Connor et al., 2000Go), but was not related to ultrasound measurements of BF or LMA. In addition, Pagan et al. (2003)Go reported that IGFBP-3 was not related to BW or ultrasound measures of BF and LMA. Bulls and heifers divergently selected for serum IGF-I concentration had similar IGFBP-2 and IGFBP-3 concentrations even though calves selected for high IGF-I concentration had 65% greater serum IGF-I concentrations than those selected for low IGF-I concentration (Pagan et al., 2003Go). This difference in IGFBP concentration relative to IGF-I concentration may have influenced the IGF-I selection line results in this study, and future research should evaluate IGFBP concentrations as well as IGF-I concentrations to better assess the use of IGF-I as an indicator trait.

Research evaluating the relationship between IGF-I concentration and RFI have yielded inconsistent results. Our results do not confirm our hypothesis, but do support previous research that demonstrated a positive genetic relationship between serum IGF-I concentration and RFI. However, our results and those from other studies indicate that the relationship between IGF-I concentration and RFI may be influenced by composition of growth and age at time of sampling for IGF-I concentration. Future research should evaluate the relationship between serum IGF-I concentration and RFI throughout the growing period to determine the age at which IGF-I should be sampled and RFI measured for use of IGF-I in selection programs to improve feed efficiency.

1 Corresponding author: g-carstens{at}tamu.edu

Received for publication April 3, 2008. Accepted for publication July 11, 2008.


   LITERATURE CITED
Top
 Abstract
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 LITERATURE CITED
 


Anderson, P. T., W. G. Bergen, R. A. Merkel, W. J. Enright, S. A. Zinn, K. R. Refsal, and D. R. Hawkins. 1988. The relationship between composition of gain and circulating hormones in growing beef bulls fed three dietary crude protein levels. J. Anim. Sci. 66:3059–3067.[Abstract/Free Full Text]

Animal Genetics and Breeding Unit. 2007. Technical update NFI & IGF-I. http://agbu.une.edu.au/cattle/beef9.pdf Accessed March 28, 2007.

AOAC. 1995. Official Methods of Analysis. 16th ed. Assoc. Off. Anal. Chem., Washington, DC.

Archer, J. A., E. C. Richardson, R. M. Herd, and P. F. Arthur. 1999. Potential for selection to improve efficiency of feed use in beef cattle: A review. Aust. J. Agric. Res. 50:147–161.[CrossRef]

Arthur, P. F., J. A. Archer, and R. M. Herd. 2004. Feed intake and efficiency in beef cattle: Overview of recent Australian research and challenges for the future. Aust. J. Exp. Agric. 44:361–369.[CrossRef]

Arthur, P. F., J. A. Archer, D. J. Johnston, R. M. Herd, E. C. Richardson, and P. F. Parnell. 2001a. Genetic and phenotypic variance and covariance components for feed intake, feed efficiency, and other postweaning traits in Angus cattle. J. Anim. Sci. 79:2805–2811.[Abstract/Free Full Text]

Arthur, P. F., G. Renand, and D. Krauss. 2001b. Genetic parameters for growth and feed efficiency in weaner versus yearling Charolais bulls. Aust. J. Agric. Res. 52:471–476.[CrossRef]

Arthur, P. F., G. Renand, and D. Krauss. 2001c. Genetic and phenotypic relationships among different measures of growth and feed efficiency in young Charolais bulls. Livest. Prod. Sci. 68:131–139.[CrossRef]

Baker, M. J., L. O. Tedeschi, D. G. Fox, W. R. Henning, and D. J. Ketchen. 2006a. Using ultrasound measurements to predict body composition of yearling bulls. J. Anim. Sci. 84:2666–2672.[Abstract/Free Full Text]

Baker, M. J., L. O. Tedeschi, D. G. Fox, W. R. Henning, and D. J. Ketchen. 2006b. Using ultrasound to determine body composition of breeding heifers. J. Anim. Sci. 84(Suppl. 1):146 (Abstr.).

Basarab, J. A., M. A. Price, J. L. Aalhus, E. K. Okine, W. M. Snelling, and K. L. Lyle. 2003. Residual feed intake and body composition in young growing cattle. Can. J. Anim. Sci. 83:189–204.

Bishop, M. D., R. C. M. Simmen, F. A. Simmen, and M. E. Davis. 1989. The relationship of insulin-like growth factor-I with postweaning performance in Angus beef cattle. J. Anim. Sci. 67:2872–2880.[Abstract/Free Full Text]

Blair, H. T., S. N. McCutcheon, D. D. Mackenzie, J. E. Ormsby, R. A. Siddiqui, B. H. Breier, and P. D. Gluckman. 1988. Genetic selection for insulin-like growth factor-I in growing mice is associated with altered growth. Endocrinology 123:1690–1692.[Abstract/Free Full Text]

Brown, E. G. 2005. Sources of Biological Variation in Residual Feed Intake in Growing and Finishing Steers. PhD Diss. Texas A&M University, College Station.

Brown, E. G., G. E. Carstens, J. T. Fox, K. O. Curley Jr., T. M. Bryan, L. J. Slay, T. H. Welsh Jr., R. D. Randel, J. W. Holloway, and D. H. Keisler. 2004. Physiological indicators of performance and feed efficiency traits in growing steers and bulls. Beef Cattle Res. Texas pp. 163–166.

Bunter, K., S. Hermesch, B. G. Luxford, K. Lahti, and E. Sutcliffe. 2002. IGF-I concentration measured in juvenile pigs provides information for breeding programs: A mini review. Proc. 7th World Congr. Genet. Appl. Livest. Prod., Montpellier, France. CD-ROM Communication No. 03–09.

Carstens, G. E., C. M. Theis, M. B. White, T. H. Welsh Jr, B. G. Warrington, R. D. Randel, T. D. A. Forbes, H. Lippke, L. W. Greene, and D. K. Lunt. 2002. Residual feed intake in beef steers: I. Correlations with performance traits and ultrasound measures of body composition. Proc. Western Sec. Am. Soc. Anim. Sci. 53:552–555.

Connor, E. E., S. M. Barao, A. S. Kimrey, A. B. Parlier, L. W. Douglass, and G. E. Dahl. 2000. Predicting growth in Angus bulls: The use of GHRH challenge, insulin-like growth factor-I, and insulin-like growth factor binding proteins. J. Anim. Sci. 78:2913–2918.[Abstract/Free Full Text]

Crews, D. H. Jr, N. H. Shannon, B. M. A. Genswein, R. E. Crews, C. M. Johnson, and B. A. Kendrick. 2003. Genetic parameters for net feed efficiency of beef cattle measured during postweaning growing versus finishing periods. Proc. West. Sec. Am. Soc. Anim. Sci. 54:125–128.

Davis, M. E., M. D. Bishop, N. H. Parks, and R. C. M. Simmen. 1995. Divergent selection for blood serum insulin-like growth factor I concentration in beef cattle: I. Nongenetic effects. J. Anim. Sci. 73:1927–1932.[Abstract]

Davis, M. E., S. L. Boyles, S. J. Moeller, and R. C. M. Simmen. 2003. Genetic parameter estimates for serum insulin-like growth factor-I concentration and ultrasound measurements of backfat thickness and longissimus muscle area in Angus beef catte. J. Anim. Sci. 81:2164–2170.[Abstract/Free Full Text]

Davis, M. E., and R. C. M. Simmen. 1997. Genetic parameter estimates for serum insulin-like growth factor-I concentration and performance traits in Angus beef cattle. J. Anim. Sci. 75:317–324.[Abstract/Free Full Text]

Davis, M. E., and R. C. M. Simmen. 2000. Genetic parameter estimates for serum insulin-like growth factor-I concentration and carcass traits in Angus beef cattle. J. Anim. Sci. 78:2305–2313.[Abstract/Free Full Text]

Davis, M. E., and R. C. M. Simmen. 2006. Genetic parameter estimates for serum insulin-like growth factor-I concentrations, and body weight and weight gains in Angus beef cattle divergently selected for serum insulin-like growth factor-I concentration. J. Anim. Sci. 84:2299–2308.[Abstract/Free Full Text]

Herd, R. M., and S. C. Bishop. 2000. Genetic variation in residual feed intake and its association with other production traits in British Hereford cattle. Livest. Prod. Sci. 63:111–119.[CrossRef]

Herd, R. M., V. H. Oddy, and E. C. Richardson. 2004. Biological basis for variation in residual feed intake in beef cattle. 1. Review of potential mechanisms. Aust. J. Exp. Agric. 44:423–430.[CrossRef]

Johnston, D. J., R. Herd, A. Reverter, and V. H. Oddy. 2001. Heritability of IGF-I in beef cattle and its association with growth and carcass traits. Proc. Assoc. Adv. Anim. Breed. Genet. 14:163–166.

Johnston, D. J., R. M. Herd, M. J. Kadel, H.-U. Graser, P. F. Arthur, and J. A. Archer. 2002. Evidence of IGF-I as a genetic predictor of feed efficiency traits in beef cattle. Pages 257–260 in Proc. 7th World Congr. Genet. Appl. Livest. Prod., Montpellier, France.

Jones, J. I., and D. R. Clemmons. 1995. Insulin-like growth factors and their binding proteins: Biological actions. Endocr. Rev. 16:3–34.[Abstract/Free Full Text]

Lund-Larsen, T. R., A. Sundby, V. Kruse, and W. Velle. 1977. Relation between growth rate, serum somatomedin and plasma testosterone in young bulls. J. Anim. Sci. 44:189–194.[Abstract/Free Full Text]

Luxford, B. G., K. L. Bunter, P. C. Owens, and R. G. Campbell. 1998. Genetic relationships between insulin-like growth factor-I and pig performance. J. Anim. Sci. 76(Suppl. 1):53 (Abstr.).

Moore, K. L., D. J. Johnston, H.-U. Graser, and R. Herd. 2005. Genetic and phenotypic relationships between insulin-like growth factor-I (IGF-I) and net feed intake, fat, and growth traits in Angus beef cattle. Aust. J. Agric. Res. 56:211–218.[CrossRef]

Nkrumah, J. D., J. A. Basarab, M. A. Price, E. K. Okine, A. Ammoura, S. Guercio, C. Hansen, C. Li, B. Murdoch, and S. S. Moore. 2004. Different measures of energetic efficiency and their phenotypic relationships with growth, feed intake, and ultrasound and carcass merit in hybrid cattle. J. Anim. Sci. 82:2451–2459.[Abstract/Free Full Text]

Oksbjerg, N., F. Gondret, and M. Vestergaard. 2004. Basic principles of muscle development and growth in meat-producing mammals as affected by the insulin-like growth factor (IGF) system. Domest. Anim. Endocrinol. 27:219–240.[CrossRef][Medline]

Pagan, M., M. E. Davis, D. A. Stick, R. C. M. Simmen, N. E. Raney, R. J. Tempelman, and C. W. Ernst. 2003. Evaluation of serum insulin-like growth factor binding proteins (IGFBP) in Angus cattle divergently selected for serum IGF-I concentration. Domest. Anim. Endocrinol. 25:345–358.[CrossRef][Medline]

Richardson, E. C., and R. M. Herd. 2004. Biological basis for variation in residual feed intake in beef cattle. 2. Synthesis of results following divergent selection. Aust. J. Exp. Agric. 44:431–440.[CrossRef]

Schenkel, F. S., S. P. Miller, and J. W. Wilton. 2004. Genetic parameters and breed differences for feed efficiency, growth, and body composition traits of young beef bulls. Can. J. Anim. Sci. 84:177–185.

Suzuki, K., M. Nakagawa, K. Katoh, H. Kadowaki, T. Shibata, H. Uchida, Y. Obara, and A. Nishida. 2004. Genetic correlation between serum insulin-like growth factor-I concentration and performance and meat quality traits in Duroc pigs. J. Anim. Sci. 82:994–999.[Abstract/Free Full Text]

Wolcott, M. L., D. J. Johnston, S. A. Barwick, and H. M. Burrow. 2006. Genetic correlations of steer growth, fatness and IGF-I with feed intake and efficiency in two tropically adapted genotypes. Proc. 8th World Congr. Genet. Appl. Livest. Prod., Belo Horizonte, Brazil http://www.wcgalp8.org.br/wcgalp8/articles/paper/14_698-1007.pdf Accessed April 3, 2007.


This article has been cited by other articles:


Home page
 J ANIM SCIHome page
S. S. Moore, F. D. Mujibi, and E. L. Sherman
Molecular basis for residual feed intake in beef cattle
J Anim Sci, April 1, 2009; 87(14_suppl): E41 - E47.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jas.2008-1083v1
86/11/2862    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lancaster, P. A.
Right arrow Articles by Welsh, T. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lancaster, P. A.
Right arrow Articles by Welsh, T. H., Jr.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS