Confirmation of a non-synonymous SNP in PNPLA8 as a candidate causal mutation for Weaver syndrome in Brown Swiss cattle

Background: Bovine progressive degenerative myeloencephalopathy (Weaver syndrome) is a neurodegenerative disorder in Brown Swiss cattle that is characterized by progressive hind leg weakness and ataxia, while sensorium and spinal reflexes remain unaffected. Although the causal mutation has not been identified yet, an indirect genetic test based on six microsatellite markers and consequent exclusion of Weaver carriers from breeding have led to the complete absence of new cases for over two decades. Evaluation of disease status by imputation of 41 diagnostic single nucleotide polymorphisms (SNPs) and a common haplotype published in 2013 identified several suspected carriers in the current breeding population, which suggests a higher frequency of the Weaver allele than anticipated. In order to prevent the reemergence of the disease, this study aimed at mapping the gene that underlies Weaver syndrome and thus at providing the basis for direct genetic testing and monitoring of today's Braunvieh/Brown Swiss herds. Results: Combined linkage/linkage disequilibrium mapping on Bos taurus chromosome (BTA) 4 based on Illumina Bovine SNP50 genotypes of 43 Weaver-affected, 31 Weaver carrier and 86 Weaver-free animals resulted in a maximum likelihood ratio test statistic value at position 49,812,384 bp. The confidence interval (0.853 Mb) determined by the 2-LOD drop-off method was contained within a 1.72-Mb segment of extended homozygosity. Exploitation of whole-genome sequence data from two official Weaver carriers and 1145 other bulls that were sequenced in Run4 of the 1000 bull genomes project showed that only a non-synonymous SNP (rs800397662) within the PNPLA8 gene at position 49,878,773 bp was concordant with the Weaver carrier status. Targeted SNP genotyping confirmed this SNP as a candidate causal mutation for Weaver syndrome. Genotyping for the candidate causal mutation in a random sample of 2334 current Braunvieh animals suggested a frequency of the Weaver allele of 0.26 %. Conclusions: Through combined use of exhaustive sequencing data and SNP genotyping results, we were able to provide evidence that supports the non-synonymous mutation at position 49,878,773 bp as the most likely causal mutation for Weaver syndrome. Further studies are needed to uncover the exact mechanisms that underlie this syndrome

The BovMAS Consortium : a complete genome scan of Brown Swiss cattle for milk yield and protein percent using selective DNA pooling with milk samples

A selective DNA pooling approach using milk samples was applied to map QTL affecting milk yield (MK) and milk protein percentage (PP). in 10 half sib daughter families of Brown Swiss sires with 1000 to 3600 individuals each. Three families were sampled in Germany, three in Italy, one in Austria and three jointly in Austria and Italy. For each sire-trait combination the 200 high and 200 low daughters, ranked by dam-corrected EBV, were chosen for selective DNA pooling. For each tail two independent pools, each of 100 daughters chosen at random, were constructed. Sire allele frequencies were obtained by densitometry at 139 evenly spaced genome-wide autosomal markers. Significance was at 5% FDR level with nominal value of about 0.04 at the marker level and 0.01 at the sire by marker level. 19 markers were significant for PP, 29 for MK, 80 for both traits, and 11 markers were not significant for either. Out of the 846 (PP) and 844 (MY) sire by marker combinations, 154 and 138 were significant for PP and MK, respectively, and 62 for both traits. From the combinations significant for at least one of the traits, MK and PP showed the same direction of the effect in 162 instances, and opposite effect in 183 instances