Deletion of the Entire CSN1S1 Gene Is Responsible for the Lack of Alpha S1-Casein in Goat (Capra hircus) Milk

In this paper we describe the characterization of a new null allele at the goat alpha s1-casein (CSN1S1) locus, so called 03^ch (ch=Carpathian), identified in Carpathian goat breed reared in Romania. A number of 975 goat milk samples, collected from 9 populations, were analyzed by isoelectrofocusing (IEF). This analysis revealed in some milk samples the apparent lack of alpha s1-casein. To verify this hypothesis we amplified the coding region of CSN1S1 cDNA from lactating goats harboring homozygous null (03^ch03^ch; N=4) and AA (N=4) genotypes. This analysis confirmed the lack of transcripts only in CSN1S1 null goats. To verify if a possible deletion at the DNA level might explain the lack of CSN1S1 gene expression in null goats, we comparatively analyzed the entire genomic region of CSN1S1 gene in AA and 03^ch03^ch goats, using specific primers designed from the sequence of A allele (AJ504710.2). We found that the entire CSN1S1 gene plus the promoter is deleted from chromosome 6 in null goats i.e. 19408 bp. Furthermore we screened a region of 109.55kb, located between 3’ ends of SULT1E1 and CSN2 genes, from chromosome 6 (goat genome reference sequence NC_022298.1). We found that significant parts from both intergenic regions are deleted. This micro-chromosomal deletion, comprising the entire CSN1S1 gene, is the first case reported in ruminant casein loci, adding important information to the knowledge of CSN1S1 polymorphism in goat. These null goats could be exploited to produce milk lacking alpha s1-casein, suitable for human subjects that are allergic to this milk protein.