Computational And Statistical Genomics
We analyze large and diverse sets of phenotypic, genotypic, and transcriptomic data to characterize sequence variants associated with molecular phenotypes, complex traits and diseases. To this end, we employ statistical workflows to perform genotype imputation, genome-wide association studies (GWAS), and other genomic analyses on high-performance computing resources. We apply innovative genome sequencing technologies, such as low-pass and long-read sequencing, to characterize the full spectrum of genomic variation. Furthermore, we investigate evolutionarily conserved non-coding regulatory features of the genome, like the branch point sequence.
Projects:
Male fertility
Insemination success and semen quality are routinely monitored in thousands of individuals in cattle and pig populations. We collaborate with Swiss artificial insemination centers to assess longitudinal data describing male fertility in large cohorts of genotyped animals. Using statistical approaches, we integrate genotype and phenotype data to search for variants that are linked to fertility disorders and quantitative variation in male reproduction. We apply in depth phenotyping approaches in collaboration with our partners to characterize the effect of trait-associated variation on the animal.
Conserved non-coding sequences of the genome
Linking genomic variation to function - and ultimately to phenotype - requires functional annotation of the genome. While the protein coding sequences of the genome are well annotated, conserved non-coding features are often poorly annotated. Our research focuses on prediction and characterization of important non-coding genomic features, such as the branch point sequence.
Publications (examples)
Kadri NK, Mapel XMM, Pausch H. The intronic branch point sequence is under strong evolutionary constraint in the bovine and human genome. Communications Biology, 2021;4:1206. external page DOI: 10.1038/s42003-021-02725-7
Nosková A, Hiltpold M, Janett F, Echtermann T, Fang ZH, Sidler X, Selige C, Hofer A, Neuenschwander S, Pausch H. Infertility due to defective sperm flagella caused by an intronic deletion in DNAH17 that perturbs splicing. Genetics, 2021;217:2. external page DOI: 10.1093/genetics/iyaa033
Hiltpold M, Niu G, Kadri NK, Crysnanto D, Fang ZH, Spengeler M, Schmitz-Hsu F, Fuerst C, Schwarzenbacher H, Seefried FR, Seehusen F, Witschi U, Schnieke A, Fries R, Bollwein H, Flisikowski K, Pausch H. Activation of cryptic splicing in bovine WDR19 is associated with reduced semen quality and male fertility. Plos Genetics, 2020;16(5):e1008804. external page DOI: 10.1371/journal.pgen.1008804
Pausch H, Schwarzenbacher H, Burgstaller J, Flisikowski K, Wurmser C, Jansen S, Jung S, Schnieke A, Wittek T, Fries R. Homozygous haplotype deficiency reveals deleterious mutations compromising reproductive and rearing success in cattle. BMC Genomics. 2015;16:312. external page DOI: 10.1186/s12864-015-1483-7
Pausch H, Kölle S, Wurmser C, Schwarzenbacher H, Emmerling R, Jansen S, Trottmann M, Fuerst C, Götz KU, Fries R. A Nonsense Mutation in TMEM95 Encoding a Nondescript Transmembrane Protein Causes Idiopathic Male Subfertility in Cattle. PLoS Genetics. 2014;10:e1004044. external page DOI: 10.1371/journal.pgen.1004044