Abstract
BackgroundCattle 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.ResultsA 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.ConclusionsExploiting 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1483-7) contains supplementary material, which is available to authorized users.
Highlights
Cattle breeding populations are susceptible to the propagation of recessive diseases
Homozygous animals were absent for FH1 and FH4, 20 and 33, respectively, were expected (P = 4.81 × 10−9 and P = 1.26 × 10−14)
Insemination success and stillbirth rate were not affected in FH2 risk matings ruling out homozygous haplotype deficiency (HHD) to result from increased pre- and perinatal mortality
Summary
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. A large proportion of the genes of current cattle breeds can be traced back to a small number of founder animals (i.e., key ancestors), mostly influential breeding bulls that have been widely used in artificial insemination [1,2]. Individuals within current cattle populations are closely related. Intense artificial selection adds to the declining effective population size (Ne) [3]. After the implementation of genome-assisted selection in many cattle breeds [6], at least the male breeding animals are routinely genotyped using dense SNP arrays in order to estimate their genetic value. Associated genome regions can be identified in studies involving phenotypically affected and unaffected animals, Pausch et al BMC Genomics (2015) 16:312 usually by performing genome-wide association studies followed by autozygosity mapping (e.g., [10])
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