Submitted to: Animal Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 22, 2001
Publication Date: N/A
Interpretive Summary: Signal peptidases are enzymes that help direct a newly produced protein to be secreted in the cell. To determine if bovine signal peptidase plays a role in the secretion of protein into milk, we cloned, sequenced, and mapped the gene in cattle. Bovine signal peptidase is very similar to other known signal peptidases from other species at both the DNA and protein level. This gene was predicted to map to bovine chromosome 14 or 27 where we believe protein secretion genes are located; however, bovine signal peptidase mapped to chromosome 21 which has not been shown to contain important genes responsible for protein yield in milk.
Technical Abstract: Signal peptidases are responsible for the removal of amino-terminal signal peptides from secretory and integral membrane proteins and are ubiquitous in nature. Studies in prokaryotes indicate that subtle sequence variations in signal peptidase affect the catalytic properties of the enzyme. Therefore, signal peptidase may be a candidate gene affecting economically important traits in dairy cattle such as milk production and, specifically protein yield due to its essential role in the secretory process. Here we report the parital genomic structure and genetic map location of the SP18 subunit. Utilizing comparative mapping resources, such as COMPASS, would place the bovine SP18 gene on either BTA14 or 27. To confirm this prediction, a SP18 BAC clone was isolated and 2 subclones were completely sequenced, identifying 3 intron/exon junctions. The genomic sequence was used to identify a SNP within one intron using the parents of the MARC reference population. Using this SNP, the bovine signal peptidase SP18 subunit gene was mapped to BTA21. The human ortholog has conflicting map information, placing the gene on both HSA8 and 15. Using Zoo-FISH data, BTA21 contains conserved regions of HSA14 and 15 and not HSA8. Therefore it is probable that the human ortholog maps to HSA15 and not HSA8. This example provides evidence that predictions based on human mapping data are not always correct and prudence should be exercised when comparative maps are generated in silico.