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

Hubert Pausch, Hermann Schwarzenbacher, Johann Burgstaller, Krzysztof Flisikowski, Christine Wurmser, Sandra Jansen, Simone Jung, Angelika Schnieke, Thomas Wittek, Ruedi Fries

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


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

Original languageEnglish
Article number312
JournalBMC Genomics
Issue number1
StatePublished - 12 Dec 2015


  • Embryonic lethality
  • Fanconi-Bickel syndrome
  • Homozygous haplotype deficiency
  • SLC2A2
  • SUGT1


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