Vertebrate Functional Genomics

Genome-wide association analysis. Research in my laboratory has been directed towards developing insight into the function of farm animal genomes to understand the genetics of monogenic and quantitative traits. Using genome-wide association analysis we have mapped genetic variation of complex phenotypes such as stature, fertility, production traits and resistance to infections. In addition, to eliminate hereditary defects, we have identified causative mutations of several monogenic diseases such as abnormal growth plate function and dwarfism in pigs, male pig infertility, bovine skeletal malformations, and bovine motor neuron dysmyelination and neurodegeneration.

Genome sequencing and annotation. Using next generation sequencing technologies, we have been involved in genome sequencing and annotation of functional genetic elements in several animal species, including pig, mink, and bowhead whale. This work provided insight into the evolutionary biology of the species as well as discovered the regulatory genomic landscapes and transcribed coding and non-coding loci associated with specific physiological and developmental stages. Such functional data are essential for understanding of how sequence variation in genes and regulatory elements determine phenotypic diversity.

The molecular genetics of vertebrate longevity and aging. The lifespan of animal species is extremely diverse, ranging from days to centuries. Current research in my laboratory is concerned with understanding the molecular genetics of extraordinary long lifespan and aging. Old age is a major risk factor for disease, suggesting that long-lived species may have evolved genetic mechanisms of resistance that match their exceptional longevity. Our goal is to identify genetic determinants and pathways in the genomes of long-lived species that provide clues as to how some animals such as the bowhead whale can live for centuries and stay free of aging-associated diseases. In addition, we use the naturally short-lived African turquoise killifish (Nothobranchius furzeri) as a model organism to understand the mechanisms underlying vertebrate longevity and aging.

Selected publications.

• Fang et al. MicroRNA-guided prioritization of genome-wide association signals reveals the importance of microRNA-target gene networks for complex traits in cattle. Scientific Reports 8, 9345 (2018)
• Bouwman et al. Meta-analysis of genome-wide association studies for cattle stature identifies common genes that regulate body size in mammals. Nature Genetics 50, 362-367 (2018)
• Cai et al. The draft reference genome of the American mink (Neovison vison) opens new opportunities of genomic research in mink. Scientific Reports 6; 7(1):14564 (2017)
• Keane et al. Insights into the evolution of longevity from the bowhead whale genome. Cell Reports 10, 112-122 (2015)
• Groenen et al. Analyses of pig genomes provide insight into porcine demography and evolution. Nature 491, 393-398 (2012).
• Jensen et al. Gene expression profiling of porcine skeletal muscle in the early recovery phase following acute physical activity. Experimental Physiology 97, 833-848 (2012)
• Thomsen et al. Congenital Bovine Spinal Dysmyelination is caused by a missense mutation in the SPAST gene. Neurogenetics 11, 175-183 (2010)
• Nielsen et al. MicroRNA identity and abundance in porcine skeletal muscles determined by deep sequencing. Animal Genetics 41, 159–168 (2010)
• Sironen et al. Infertile Finnish Yorkshire boars carry a full-length LINE-1 retrotransposon within the KPL2 gene. Molecular Genetics and Genomics 278, 385-391 (2007)
• Thomsen et al. A missense mutation in the bovine SLC35A3 gene, encoding a UDP-N-acetylglucosamine transporter, causes complex vertebral malformation. Genome Research 16, 97-105 (2006)
• Sironen et al. An intronic insertion in KPL2 results in aberrant splicing and causes the immotile short-tail sperm defect in the pig. Proceedings of the National Academy of Sciences U S A. 103, 5006-5011 (2006)
• Nielsen et al. Abnormal growth plate function in pigs carrying a dominant mutation in type X collagen. Mammalian Genome 11, 1087-1092 (2000)