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Title: ALLELES OF THE CHOLESTEROL 7 ALPHA-HYDROXYLASE (CYP7) GENE IN PIGS SELECTEDFOR HIGH OR LOW PLASMA TOTAL CHOLESTEROL

Author
item DAVIS, A. - UNIVERSITY OF ILLINOIS
item POND, W. - BAYLOR COLLEGE OF MED
item WHEELER, M. - UNIVERSITY OF ILLINOIS
item ISHIMURA-OKA, K. - BAYLOR COLLEGE OF MED
item SU, D. - BAYLOR COLLEGE OF MED
item LI, C. - BAYLOR COLLEGE OF MED
item Mersmann, Harry

Submitted to: American Society for Experimental Biology and Medicine Proceedings
Publication Type: Proceedings
Publication Acceptance Date: 10/29/1997
Publication Date: N/A
Citation: N/A

Interpretive Summary: Pigs have been genetically selected for high or low blood cholesterol concentration. After eight generations, the blood cholesterol was about 1.7 times greater in the pigs selected for high compared to low cholesterol. It was discovered that the pigs selected for high and low blood cholesterol had distinct forms of a gene for an enzyme involved in bile acid synthesis. Bile acid synthesis is one of the major pathways use to eliminate cholesterol from the body. The most characterized model for high blood cholesterol in pigs has a defect in the uptake of cholesterol by tissues, thus yielding high blood cholesterol concentration. Our model represents a genetic modification in a gene for the elimination of cholesterol, thus another animal model is available to study cholesterol metabolism. The genetics have been characterized, but the complete picture of cholesterol metabolism in these pigs remains to be studied.

Technical Abstract: Crossbred pigs were selected for high (HTC) or low LTC) plasma total cholesterol (TC). Pigs from the seventh (n=51) and eighth (n=92) generations were used to determine restriction fragment length polymorphisms (RFLP). Using TaqI restriction enzyme digestion, the frequencies of two alleles (2.8- or 5.0-kb fragments) of the cholesterol 7 alpha-hydroxylase (CYP7) gene were determined in the two populations as a potential indicator of TC concentration at 8 weeks of age. Only the 2.8-kb fragment allele was present at the 26 HTC pigs tested in Generation 7. In the LTC pigs both the 2.8- and 5.0-kb alleles were present in 12 pigs, and only the 5.0-kb allele was present in 13 pigs. The allele frequencies of the 2.8 and 5.0 fragments, respectively, were .26 and .74 in LTC pigs and 1.00 and 0 in HTC pigs. There was an association (P<.001) between the 5.0- and 2.8-kb CYP7 alleles, respectively, and low and high TC concentrations. In Generation 8, all HTC pigs were homozygous for the 2.8-kb allele. The 5.0 kb allele was present in all LTC pigs tested and was homozygous in 57% of LTC pigs. Mean plasma TC was 105.0 mg/dl in 30 pigs homozygous for the 2.8-kb allele in Generation 8; means for LTC pigs were 53.5 and 60.4 mg/dl in 35 pigs homozygous for the 5.0-kb allele and in 27 heterozygous pigs, respectively. High TC was associated with the presence of the 2.8-kb allele, and low TC was associated with the presence of the 5.0-kb allele in both Generations 7 and 8. We conclude that TaqI RFLP analysis of the CYP7 gene is a reliable indicator for TC in these swine.