title: Aberrant low expression level of bovine beta-lactoglobulin is associated with a C to A transversion in the BLG promoter region.
abstract: Beta-lactoglobulin (beta-LG) is the major whey protein in cow's milk. It is well established that the predominant 2 genetic variants, beta-LG A and B, are differentially expressed. Extensive investigation of the genetic variation in the promoter region of the BLG gene revealed the existence of specific haplotypes associated with the A and B variants, respectively. However, the genetic basis for the differential expression of BLG A and B alleles is still elusive. We have previously reported a quantitative beta-LG B variant, characterized by a very low beta-LG protein expression level. Here, we report that the corresponding BLG allele (BLG B*) shows a correspondingly low mRNA expression level. Comparative DNA sequencing of 7,670 bp of the BLG B* allele and the established BLG B allele revealed a unique difference of a C to A transversion at position 215 bp upstream of the translation initiation site (g.-215C>A). This mutation segregated perfectly with the differential phenotypic expression in a paternal half-sib family and could be confirmed in 2 independent cases. The sequence of the BLG B allele in the region of the mutation is highly conserved among 4 related ruminant species. The site of the mutation corresponds to a putative consensus-binding sequence for the transcription factors c-Rel and Elk-1 as predicted by searching the TRANSFAC database. The beta-LG B* site might be relevant in the natural production of milk of low beta-LG content.
authors.affiliation: Institute of Genetics, University of Berne, CH-3001 Berne, Switzerland. martin.braunschweig@itz.unibe.ch
authors.forename: M H
authors.initials: MH
authors.lastname: Braunschweig
authors.forename: T
authors.initials: T
authors.lastname: Leeb
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D002417:Cattle / Q000235:genetics / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D007782:Lactoglobulins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D008297:Male; D008892:Milk / Q000737:chemistry; D008894:Milk Proteins / Q000032:analysis; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000662:veterinary; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: D007782:Lactoglobulins; D008894:Milk Proteins