BACKGROUND
in response to the constant bombardment of health-related stories, consumers are becoming more health conscious and are becoming increasingly aware of the amount and type of fats and fatty acids they consume.
red meat is often perceived as a fatty protein source with certain health risks associated with its consumption.
beef could be viewed more favorably from a human health standpoint if strategies could be applied to decrease saturated fatty acid  content while increasing the concentration of beneficial polyunsaturated fatty acids , especially omega- <dig> pufa, and conjugated linoleic acid.
beef producers continue to strive to produce a high quality product that meets consumer demands in a cost-effective manner.
while fatty acid profiles can be altered through the diet  <cit> , identification of genetic markers that would allow producers to select beef for altered fatty acid composition could ultimately increase value and consumer satisfaction with beef.
while producers have recently selected cattle with a higher propensity to marble, because of the premiums that they are paid, some consumers favor lower concentrations of sfa because of their perceived negative effect on human health.
therefore, the goal of the present study was to assess the utility of genetic markers to select for fatty acids composition, identify regions of the genome that account for genetic variation, and evaluate genome architecture of fatty acid regulation.
RESULTS
summary statistics for the fatty acid phenotypes analyzed in this study are reported in table  <dig>
1
2
1the amount of fatty acid in  <dig> gram beef meat.
2the percent of fatty acid in total fatty acid.
3n- <dig> fatty acids.
4n- <dig> fatty acids.
5atherogenic index.
6na = not analyzed.
posterior genetic and residual variances and heritability
the discovery process generates an estimate, similar to pedigree-based heritability, of the proportion of phenotypic variation that can be accounted for using snp markers for each of the fatty acids studied on a beef meat or fat percent basis .
the proportion of phenotypic variance explained  by snp genotypes varied from a very low amount  for 18:1c <dig>  18:1t6pt <dig>  18:3n <dig>  and 20:3n <dig>  which indicates that the marker predictions will be poor, to relatively high  for 14: <dig>  14: <dig> : <dig>  16: <dig>  18: <dig>  18:1c <dig> and 24: <dig>  which indicates potential for relatively good marker predictions.
in general, the percentage of phenotypic variance explained by markers was higher when fatty acids were analyzed on a fat percent compared with beef basis.
this result is not unexpected given that, on a beef basis, the level of any given fatty acid is influenced by both its relative amount in comparison to other fatty acids as well as the amount of lipid present in the given sample.
in contrast, on a fat percent basis, only variation relative to other fatty acids is taken into account.
if total fatty acid content is included as a covariate when analyzing fatty acids on a beef basis, heritabilities similar to a weight percent basis are obtained .
this comparison would indicate that much of the variation in heritability estimates between methods result from variation in total fatty acid content.
on a fat percent basis, fatty acids with chain length > <dig> carbons , had lower heritability  than shorter chain fatty acids .
this heritability difference might indicate that genes involved in the production and/or metabolism of these longer-chain fatty acids are under selective pressure to minimize variation.
alternatively, given the fact that de novo fatty acid synthesis in cattle is limited to primarily  <dig>   <dig> and  <dig> carbon fatty acids  <cit> , it is possible that the observed variation in longer chain fatty acids result from host genetic variation influencing the population of rumen microbiota, which modify ingested fatty acids  <cit> .
1
2
1the amount of fatty acid in  <dig> gram beef meat.
2the percent of fatty acid in total fatty acid.
3n- <dig> fatty acids.
4n- <dig> fatty acids.
5atherogenic index.
6na = not analyzed.
medium-chain saturated fatty acids like 12: <dig>  14: <dig> and 16: <dig> have been associated with increased incidence of cardiovascular disease  <cit> ).
in contrast, longer-chained and unsaturated fatty acids are considered to be either neutral or even possibly protective  <cit> .
given the relatively high amount of phenotypic variance in 14: <dig>  16: <dig>  18: <dig>  18:1c <dig>  /all and ai that variation that can be accounted for by molecular markers, it should be possible to select for a more heart healthy fatty acid composition.
direct genomic breeding values  coefficients, correlations and accuracy
the numbers of individuals in each k-means clustered group are shown in table  <dig>  the pooled regression coefficients and the simple correlations between dgv and phenotypes over  <dig> k-means clustered groups, and the realized accuracies of dgv for some fatty acid traits are in table  <dig>  the pooled regression coefficient ranged from  <dig>  for clac9t <dig> to - <dig>  for 20:3n <dig>  the pooled simple correlation ranged from  <dig>  for 14: <dig>  mcfa, and ai to - <dig>  for 20:3n <dig>  while the accuracies of genomic prediction varied from  <dig>  for 14: <dig>  lcfa, and mcfa to - <dig>  for 20:3n <dig> .
given the higher accuracies associated with 14: <dig> and 16: <dig>  it should be possible to develop a selection index to minimize these two fatty acids.
alternatively, producers could use ratios like /all or ai to select for animals that have decreased levels of shorter chain saturated fatty acids.
1combined from two primarily k-means clustered groups with sizes of  <dig> and  <dig>
<dig>
of dgv for some fatty acid traits as percent in total fatty acid
b
r
1as the pooled simple correlations between dgv and phenotypes in validation groups divided by the square root of trait heritability.
whole genome association
the 1-mb snp windows with the highest genetic variances and a posterior probability of having non-zero genetic variance greater than 90%  for fatty acids on a fat percent  and beef basis , respectively.
the proportion of genetic variance explained by 1-mb snp windows ranged from  <dig> % for 18:3n <dig> to  <dig> % for 24: <dig>  on a fat percent basis, and  <dig> % for 10: <dig> and  <dig> % for 24: <dig> on a beef basis .
many of the 1-mb windows were associated with more than one fatty acid.
for example, the 51st mb window on chromosome  <dig> was associated with 14: <dig>  14: <dig>  16: <dig>  16: <dig>  18:1c <dig>  lcfa, mcfa, mufa, sfa, /all, and ai on a fat percent basis.
whereas, only the 49th mb on chromosome  <dig> was associated with 17: <dig> .
no other region on chromosome  <dig> was associated with any other fatty acid.
1
2
1bovine chromosome and nth 1-mb window of the same chromosome started from zero, based on umd  <dig> .
2posterior probability of inclusion .
1
2
1bovine chromosome and nth 1-mb window of the same chromosome started from zero, based on umd  <dig> .
2posterior probability of inclusion .
many of the 1-mb windows that were identified harbored good candidate genes.
for example, fatty acid synthase  is located on chromosome  <dig> between  <dig> , <dig> and  <dig> , <dig> bp, which is almost exactly in the middle of this 1-mb window.
previously, our group reported that variants in fasn were associated with fatty acid composition in angus  <cit> .
in addition, fasn has been reported to be associated with bovine adipose composition, milk fat content, and fatty acid composition of beef in several different breeds of cattle, which indicates that it has a conserved role across genetic backgrounds  <cit> .
interestingly, there are several different variants that are responsible for fasn effects in the different breeds  <cit> .
furthermore, sterol-coa desaturase  is located on chromosome  <dig> between  <dig> , <dig> and  <dig> , <dig> bp, which is at the edge of a 1-mb window associated with 14: <dig>  14: <dig>  16: <dig>  cis- <dig> 18: <dig>  sfa, and ai .
previously, scd variants have been reported to be associated with fatty acid composition of meat and milk fat  <cit> .
in contrast, other 1-mb regions contain no obvious candidate genes, for example the 20th mb window on chromosome  <dig> that is associated with cis- <dig> 18: <dig>  after the 1-mb window that harbors fasn, a region on chromosome  <dig>  could account for the second greatest amount of genetic variance in 14: <dig>  14: <dig>  16: <dig>  16: <dig>  cis- <dig> c18: <dig>  lcfa, and mcfa.
this region has not previously been reported to be associated with any adipose trait other than subcutaneous fat thickness   <cit> .
interestingly, thyroid hormone responsive  has been reported to act at the level of transcription to regulate genes that encode enzymes required for long-chain fatty acid synthesis  <cit> .
in addition in knockout studies, it has been reported that thrsp null mice showed a marked deficiency in de novo lipogenesis.
moreover, knockout studies have also revealed that thrsp may work in the cytoplasm by tethering fasn to the microtubule  <cit> .
thus, it would appear that thrsp is a good candidate gene, which was recently reported to be associated with fatty acid composition in korean cattle  <cit> .
it should be noted that none of the 1-mb windows that harbor srebp <dig>  acaca, pparg, fabp <dig>  acsl <dig>  lep, or lxra, which are all genes that have been previously associated with fatty acid composition in beef  <cit> , were associated with variation in any fatty acid in this study.
when taken in concert with the fact that different fasn alleles appear to be segregating in different breeds  <cit> , this may indicate that the genetic mechanisms controlling fatty acid composition may vary greatly from breed to breed.
this is further supported by the fact that the fasn region in japanese black cattle appears to account for the vast majority of the genetic variance, while in contrast several regions are reported here for american angus.
within regions correlation
the correlations between dgv within 19_ <dig>  26_ <dig> and 29_ <dig> windows  for each pair of c14: <dig>  c14: <dig>  c16: <dig>  c16: <dig>  c18: <dig> and cis- <dig> c18: <dig> fatty acids on the fat percent basis are summarized in figure  <dig>  there are two clear patterns in the within windows estimated correlations between fatty acid.
the first pattern involves the regions located on chromosome  <dig>  and  <dig> , which harbor fasn and thrsp as candidate genes, respectively.
estimates of the dgv correlations were very high and positive among 14: <dig>  14: <dig>  16: <dig> and 16: <dig>  however regional dgv correlation between this group of fatty acids and 18: <dig> and cis- <dig> 18: <dig> were large and negative.
while the dgv correlation between 18: <dig> and cis- <dig> 18: <dig> were very high and positive.
regions 19_ <dig> and 29_ <dig> were found to be associated to all fatty acids except for 18: <dig>  where only the region on chromosome  <dig> was identified .
these results indicate that both, fasn and thrsp, exhibit pleiotropic effects for most fatty acids and act in a coordinate manner to contribute to the formation of fatty acid involved in de novo synthesis.
however, for the formation of 18: <dig> and cis- <dig> 18: <dig> a different elongase  <cit>  is required.
therefore, the negative correlation may indicate competition between enzymes for the same substrate.
the second correlation pattern involves the region on chromosome  <dig> , which harbors scd.
correlations were in general lower than the ones obtained in the previous two regions.
the within region correlation between the 14: <dig>  16: <dig> and 18: <dig> were all strong and positive.
weaker positive correlations were also observed with 16: <dig>  however, the correlations of dgv for those fatty acids with 14: <dig> and cis <dig> 18: <dig> were negative.
figure  <dig> summarize the within regions correlations among the same fatty acids on the beef meat basis.
the same patterns of correlations were obtained on the beef basis as those obtained for fat percentage basis except for 16: <dig>  and cis <dig> 18: <dig>  where no qtl was detected on these regions for these fatty acids on the beef basis analysis .
patterns of correlations illustrate how the selection to change fatty acid composition of fat could have a differential effect depending upon the region that is affected by selection.
thus, the use of genomic information creates an opportunity for a more precise selection by using specific regions information rather than pedigree based selection.
on the other hand, we have been assuming that the observed correlations are due to pleiotropic effects, which might not be the case.
to what extent the correlations are due to selection for increased marbling in the angus population is unknown.
CONCLUSIONS
this study is the first genome selection and genome wide association analyses for fatty acid composition in american angus sired cattle.
fatty acid composition is of paramount importance due to their role in cardiovascular health.
the genetic dissection of fatty acid composition could lead to a better understanding of the molecular mechanisms that control fatty acid content in meat.
we utilized a large angus-sired population to calculate genomic breeding values of individual animals and to identify genomic regions harboring genetic variation associated with fatty acid composition.
molecular markers were able to account for between  <dig> and 57% of the observed variance in an individual fatty acid.
in addition, the accuracy of the dgv  ranged from - <dig>  to  <dig> .
furthermore, we identified  <dig> 1-mb windows with a posterior probability of inclusion  that harbor genetic variation associated with individual fatty acid content.
this large number of genomic regions might indicate the presence of an elaborate molecular mechanism that control fatty acid content in skeletal muscle.
in addition, the correlation of dgv among the different fatty acids within specific genomic regions might help to articulate the genetic correlations between any two traits.
taken together these results provide the most comprehensive evaluation of the genetic mechanisms that control fatty acid composition in skeletal muscle.

 in response to the constant bombardment of health-related stories, consumers are becoming more health conscious and are becoming increasingly aware of the amount and type of fats and fatty acids they consume. red meat is often perceived as a fatty protein source with certain health risks associated with its consumption. beef could be viewed more favorably from a human health standpoint if strategies could be applied to decrease saturated fatty acid content while increasing the concentration of beneficial polyunsaturated fatty acids, especially omega- pufa, and conjugated linoleic acid. beef producers continue to strive to produce a high quality product that meets consumer demands in a cost-effective manner. while fatty acid profiles can be altered through the diet, identification of genetic markers that would allow producers to select beef for altered fatty acid composition could ultimately increase value and consumer satisfaction with beef. while producers have recently selected cattle with a higher propensity to marble, because of the premiums that they are paid, some consumers favor lower concentrations of sfa because of their perceived negative effect on human health. therefore, the goal of the present study was to assess the utility of genetic markers to select for fatty acids composition, identify regions of the genome that account for genetic variation, and evaluate genome architecture of fatty acid regulation.  summary statistics for the fatty acid phenotypes analyzed in this study are reported in table  1 2 1the amount of fatty acid in gram beef meat. 2the percent of fatty acid in total fatty acid. 3n- fatty acids. 4n- fatty acids. 5atherogenic index. 6na = not analyzed. posterior genetic and residual variances and heritability the discovery process generates an estimate, similar to pedigree-based heritability, of the proportion of phenotypic variation that can be accounted for using snp markers for each of the fatty acids studied on a beef meat or fat percent basis. the proportion of phenotypic variance explained by snp genotypes varied from a very low amount for 18:1c 18:1t6pt 18:3n and 20:3n which indicates that the marker predictions will be poor, to relatively high for 14: 14:: 16: 18: 18:1c and 24: which indicates potential for relatively good marker predictions. in general, the percentage of phenotypic variance explained by markers was higher when fatty acids were analyzed on a fat percent compared with beef basis. this result is not unexpected given that, on a beef basis, the level of any given fatty acid is influenced by both its relative amount in comparison to other fatty acids as well as the amount of lipid present in the given sample. in contrast, on a fat percent basis, only variation relative to other fatty acids is taken into account. if total fatty acid content is included as a covariate when analyzing fatty acids on a beef basis, heritabilities similar to a weight percent basis are obtained. this comparison would indicate that much of the variation in heritability estimates between methods result from variation in total fatty acid content. on a fat percent basis, fatty acids with chain length > carbons, had lower heritability than shorter chain fatty acids. this heritability difference might indicate that genes involved in the production and/or metabolism of these longer-chain fatty acids are under selective pressure to minimize variation. alternatively, given the fact that de novo fatty acid synthesis in cattle is limited to primarily and carbon fatty acids, it is possible that the observed variation in longer chain fatty acids result from host genetic variation influencing the population of rumen microbiota, which modify ingested fatty acids. 1 2 1the amount of fatty acid in gram beef meat. 2the percent of fatty acid in total fatty acid. 3n- fatty acids. 4n- fatty acids. 5atherogenic index. 6na = not analyzed. medium-chain saturated fatty acids like 12: 14: and 16: have been associated with increased incidence of cardiovascular disease ). in contrast, longer-chained and unsaturated fatty acids are considered to be either neutral or even possibly protective. given the relatively high amount of phenotypic variance in 14: 16: 18: 18:1c /all and ai that variation that can be accounted for by molecular markers, it should be possible to select for a more heart healthy fatty acid composition. direct genomic breeding values coefficients, correlations and accuracy the numbers of individuals in each k-means clustered group are shown in table  the pooled regression coefficients and the simple correlations between dgv and phenotypes over k-means clustered groups, and the realized accuracies of dgv for some fatty acid traits are in table  the pooled regression coefficient ranged from for clac9t to - for 20:3n the pooled simple correlation ranged from for 14: mcfa, and ai to - for 20:3n while the accuracies of genomic prediction varied from for 14: lcfa, and mcfa to - for 20:3n. given the higher accuracies associated with 14: and 16: it should be possible to develop a selection index to minimize these two fatty acids. alternatively, producers could use ratios like /all or ai to select for animals that have decreased levels of shorter chain saturated fatty acids. 1combined from two primarily k-means clustered groups with sizes of and of dgv for some fatty acid traits as percent in total fatty acid b r 1as the pooled simple correlations between dgv and phenotypes in validation groups divided by the square root of trait heritability. whole genome association the 1-mb snp windows with the highest genetic variances and a posterior probability of having non-zero genetic variance greater than 90% for fatty acids on a fat percent and beef basis, respectively. the proportion of genetic variance explained by 1-mb snp windows ranged from % for 18:3n to % for 24: on a fat percent basis, and % for 10: and % for 24: on a beef basis. many of the 1-mb windows were associated with more than one fatty acid. for example, the 51st mb window on chromosome was associated with 14: 14: 16: 16: 18:1c lcfa, mcfa, mufa, sfa, /all, and ai on a fat percent basis. whereas, only the 49th mb on chromosome was associated with 17:. no other region on chromosome was associated with any other fatty acid. 1 2 1bovine chromosome and nth 1-mb window of the same chromosome started from zero, based on umd. 2posterior probability of inclusion. 1 2 1bovine chromosome and nth 1-mb window of the same chromosome started from zero, based on umd. 2posterior probability of inclusion. many of the 1-mb windows that were identified harbored good candidate genes. for example, fatty acid synthase is located on chromosome between, and, bp, which is almost exactly in the middle of this 1-mb window. previously, our group reported that variants in fasn were associated with fatty acid composition in angus. in addition, fasn has been reported to be associated with bovine adipose composition, milk fat content, and fatty acid composition of beef in several different breeds of cattle, which indicates that it has a conserved role across genetic backgrounds. interestingly, there are several different variants that are responsible for fasn effects in the different breeds. furthermore, sterol-coa desaturase is located on chromosome between, and, bp, which is at the edge of a 1-mb window associated with 14: 14: 16: cis- 18: sfa, and ai. previously, scd variants have been reported to be associated with fatty acid composition of meat and milk fat. in contrast, other 1-mb regions contain no obvious candidate genes, for example the 20th mb window on chromosome that is associated with cis- 18: after the 1-mb window that harbors fasn, a region on chromosome could account for the second greatest amount of genetic variance in 14: 14: 16: 16: cis- c18: lcfa, and mcfa. this region has not previously been reported to be associated with any adipose trait other than subcutaneous fat thickness. interestingly, thyroid hormone responsive has been reported to act at the level of transcription to regulate genes that encode enzymes required for long-chain fatty acid synthesis. in addition in knockout studies, it has been reported that thrsp null mice showed a marked deficiency in de novo lipogenesis. moreover, knockout studies have also revealed that thrsp may work in the cytoplasm by tethering fasn to the microtubule. thus, it would appear that thrsp is a good candidate gene, which was recently reported to be associated with fatty acid composition in korean cattle. it should be noted that none of the 1-mb windows that harbor srebp acaca, pparg, fabp acsl lep, or lxra, which are all genes that have been previously associated with fatty acid composition in beef, were associated with variation in any fatty acid in this study. when taken in concert with the fact that different fasn alleles appear to be segregating in different breeds, this may indicate that the genetic mechanisms controlling fatty acid composition may vary greatly from breed to breed. this is further supported by the fact that the fasn region in japanese black cattle appears to account for the vast majority of the genetic variance, while in contrast several regions are reported here for american angus. within regions correlation the correlations between dgv within 19_ 26_ and 29_ windows for each pair of c14: c14: c16: c16: c18: and cis- c18: fatty acids on the fat percent basis are summarized in figure  there are two clear patterns in the within windows estimated correlations between fatty acid. the first pattern involves the regions located on chromosome and, which harbor fasn and thrsp as candidate genes, respectively. estimates of the dgv correlations were very high and positive among 14: 14: 16: and 16: however regional dgv correlation between this group of fatty acids and 18: and cis- 18: were large and negative. while the dgv correlation between 18: and cis- 18: were very high and positive. regions 19_ and 29_ were found to be associated to all fatty acids except for 18: where only the region on chromosome was identified. these results indicate that both, fasn and thrsp, exhibit pleiotropic effects for most fatty acids and act in a coordinate manner to contribute to the formation of fatty acid involved in de novo synthesis. however, for the formation of 18: and cis- 18: a different elongase is required. therefore, the negative correlation may indicate competition between enzymes for the same substrate. the second correlation pattern involves the region on chromosome, which harbors scd. correlations were in general lower than the ones obtained in the previous two regions. the within region correlation between the 14: 16: and 18: were all strong and positive. weaker positive correlations were also observed with 16: however, the correlations of dgv for those fatty acids with 14: and cis 18: were negative. figure  summarize the within regions correlations among the same fatty acids on the beef meat basis. the same patterns of correlations were obtained on the beef basis as those obtained for fat percentage basis except for 16: and cis 18: where no qtl was detected on these regions for these fatty acids on the beef basis analysis. patterns of correlations illustrate how the selection to change fatty acid composition of fat could have a differential effect depending upon the region that is affected by selection. thus, the use of genomic information creates an opportunity for a more precise selection by using specific regions information rather than pedigree based selection. on the other hand, we have been assuming that the observed correlations are due to pleiotropic effects, which might not be the case. to what extent the correlations are due to selection for increased marbling in the angus population is unknown.  this study is the first genome selection and genome wide association analyses for fatty acid composition in american angus sired cattle. fatty acid composition is of paramount importance due to their role in cardiovascular health. the genetic dissection of fatty acid composition could lead to a better understanding of the molecular mechanisms that control fatty acid content in meat. we utilized a large angus-sired population to calculate genomic breeding values of individual animals and to identify genomic regions harboring genetic variation associated with fatty acid composition. molecular markers were able to account for between and 57% of the observed variance in an individual fatty acid. in addition, the accuracy of the dgv ranged from - to. furthermore, we identified 1-mb windows with a posterior probability of inclusion that harbor genetic variation associated with individual fatty acid content. this large number of genomic regions might indicate the presence of an elaborate molecular mechanism that control fatty acid content in skeletal muscle. in addition, the correlation of dgv among the different fatty acids within specific genomic regions might help to articulate the genetic correlations between any two traits. taken together these results provide the most comprehensive evaluation of the genetic mechanisms that control fatty acid composition in skeletal muscle. 
further investigations are needed to identify the causal variants harbored within the identified 1-mb windows. 1-mb regions on bta bta and bta which harbored fatty acid synthase, sterol-coa desaturase and thyroid hormone responsive candidate genes, respectively, explained a high percentage of genetic variance in more than one fatty acid. furthermore, 1-mb regions were identified that were associated with at least one fatty acid with a posterior probability of inclusion greater than. furthermore, these reported results could improve our understanding of the biology of fatty acid metabolism and deposition. therefore, the objective of this study was to determine the extent to which molecular markers could account for variation in fatty acid composition of skeletal muscle and identify genomic regions that harbor genetic variation. subsets of markers on the illumina 54k bovine snpchip were able to account for up to 57% of the variance observed in fatty acid composition. for the first time, angus breeders have a tool whereby they could select for altered fatty acid composition. one such nutrient is fatty acids, which have been implicated as playing a role in cardiovascular disease. in addition, these markers could be used to calculate a direct genomic breeding values for a given fatty acids with an accuracy ranging from - to. it was also observed that the correlation between dgv for different fatty acids at a given 1-mb window ranged from almost to - 
 as consumers continue to request food products that have health advantages, it will be important for the livestock industry to supply a product that meet these demands. one such nutrient is fatty acids, which have been implicated as playing a role in cardiovascular disease. therefore, the objective of this study was to determine the extent to which molecular markers could account for variation in fatty acid composition of skeletal muscle and identify genomic regions that harbor genetic variation.  subsets of markers on the illumina 54k bovine snpchip were able to account for up to 57% of the variance observed in fatty acid composition. in addition, these markers could be used to calculate a direct genomic breeding values for a given fatty acids with an accuracy ranging from - to. furthermore, 1-mb regions were identified that were associated with at least one fatty acid with a posterior probability of inclusion greater than. 1-mb regions on bta bta and bta which harbored fatty acid synthase, sterol-coa desaturase and thyroid hormone responsive candidate genes, respectively, explained a high percentage of genetic variance in more than one fatty acid. it was also observed that the correlation between dgv for different fatty acids at a given 1-mb window ranged from almost to -  further investigations are needed to identify the causal variants harbored within the identified 1-mb windows. for the first time, angus breeders have a tool whereby they could select for altered fatty acid composition. furthermore, these reported results could improve our understanding of the biology of fatty acid metabolism and deposition. intramuscular fatgenome architectureangus 