The extensive use of a limited number of elite bulls in cattle breeding can lead to rapid spread of recessively inherited disorders. A recent example is the globally distributed syndrome Complex Vertebral Malformation (CVM), which is characterized by misshapen and fused vertebrae around the cervico-thoracic junction. Here, we show that CVM is caused by a mutation in the Golgi-resident nucleotide-sugar transporter encoded by SLC35A3. Thus, the disease showed complete cosegregation with the mutation in a homozygous state, and proteome patterns indicated abnormal protein glycosylation in tissues of affected animals. In addition, a yeast mutant that is deficient in the transport of UDP-N-acetylglucosamine into its Golgi lumen can be rescued by the wild-type SLC35A3 gene, but not by the mutated gene. These results provide the first demonstration of a genetic disorder associated with a defective SLC35A3 gene, and reveal a new mechanism for malformation of the vertebral column caused by abnormal nucleotide-sugar transport into the Golgi apparatus.

No abstract

No abstract

Melanocortin 4 receptor (MC4R) is expressed in the appetite-regulating areas of the brain where it is central in the regulation of feed intake and energy balance. A mutation in MC4R causing an Asp298Asn substitution has been associated with fatness, high daily gain and feed intake in the pig. In a previously performed genome scan based on a Hampshire x Landrace cross, we detected one quantitative trait loci (QTL) affecting carcass fat/meat ratio and one QTL affecting the biceps femoris muscle, both close to the position of MC4R on porcine chromosome 1. In this study, the two lines were found to be close to fixation for alternative alleles of the Asp298Asn polymorphism. Additional QTL analyses supported our hypothesis of MC4R as a positional candidate gene but only for the fat/meat QTL. The Asp298Asn polymorphism was also evaluated as a selection target for daily gain in a Danish pig breeding population that included four breeds (Hampshire, Duroc, Landrace and Yorkshire). Over a 12-year period (1990-2002), a significant increase in the allele frequency of 298Asn was found in Landrace and Duroc, whereas a non-significant decrease in the 298Asn allele frequency was observed in Yorkshire. The Hampshire breed was fixed for the 298Asn allele in 1990. The high 298Asn allele frequencies in Hampshire, Landrace and Duroc are most likely due to selection for daily gain, whereas selection for daily gain in the Yorkshire breed apparently focuses on other loci.