Homozygous haplotype deficiency reveals deleterious mutations compromising reproductive and rearing success in cattle

• DOI: 10.1186/s12864-015-1483-7
• Publication Date: 2015-04-17T00:23:56Z
• Authors: Hubert Pausch; Hermann Schwarzen...; Johann Burgstaller; Krzysztof Flisiko...; Christine Wurmser; Sandra Jansen; Simone Jung; Angelika Schnieke; Thomas Wittek; Ruedi Fries
• Keywords: Runs of Homozygosity

Cattle breeding populations are susceptible to the propagation of recessive diseases. Individual sires generate tens thousands progeny via artificial insemination. The frequency deleterious alleles carried by such may increase considerably within few generations. Deleterious manifest themselves often missing homozygosity resulting from embryonic/fetal, perinatal or juvenile lethality homozygotes. A scan for homozygous haplotype deficiency in 25,544 Fleckvieh cattle uncovered four haplotypes affecting reproductive and rearing success. Exploiting whole-genome resequencing data 263 animals facilitated pinpoint putatively causal mutations two these haplotypes. mutation causing an evolutionarily unlikely substitution SUGT1 was perfectly associated with a compromising insemination not found state 10,363 (P = 1.79 × 10−5) is thus likely cause embryos. frameshift SLC2A2 encoding glucose transporter 2 (GLUT2) compromises calf survival. leads premature termination translation activates cryptic splice sites multiple exon variants also termination. affected calves exhibit stunted growth, resembling phenotypic appearance Fanconi-Bickel syndrome humans (OMIM 227810), which caused SLC2A2. comprehensive genotype sequence enabled us reveal that compromise pre- postnatal survival state. Our results provide basis genome-assisted approaches avoiding inadvertent carrier matings improving success cattle.