Kerstin Lindblad-Toh

Kerstin Lindblad-Toh
Uppsala University and Broad Institute

Research Interests

Professor Lindblad-Toh’s research interests span a broad range of areas including 1) deciphering the function of the human genome, 2) understanding mechanisms for genome evolution and the connection to phenotypic adaptations 3) identification of disease genes in both dogs and humans.

The sequencing and comparative analysis of 29 mammals has been key for identifying the functional elements in the human genome. This resource is now being expanded towards 200 sequenced mammals, which should give single base resolution for constraint in the human genome. This will be a fantastic resource, which can allow not only detection of constraint (functional importance) but also find regions under positive selection in specific species.

In addition, key species are studied for the their value for understanding biological or evolutionary mechanisms. Examples include the anolis lizzard, coelacanth and five cichlids as well as species with intriguing domestication histories such as the rabbit and the dog.

A major emphasis in the lab using the dog as a comparative model for human diseases based on the similarities of diseases found in dogs and humans. In addition, mapping genes is much easier in dogs due to a relative genetic homogeneity within breeds. The group studies more than 20 diseases including cancer and autoimmune, and neurological diseases and has identified new genes and disease pathways for several of these.

Many of the canine findings are now being translated to human patients cohorts. A particular focus is the resequencing of hundreds of target genes and their regulatory elements in well-characterized patient materials to identify mutations linked to overall disease or specific sub-phenotypes. Among others this includes a 1900 gene study, where genes were selected based on canine candidate genes and pathways together with human disease genes and where several autoimmune and autoinflammatory diseases, including SLE, are now being carefully examined and compared.

Group members

Jennifer Meadows, Researcher
Sergey Kozyrev, Researcher
Ingegerd (Ginger) Elvers, Researcher
Voichita (Vikki) Marinescu, Researcher
Maja Arendt, Postdoc
Marcin Kierczak, Postdoc
Nina Oparina, Postdoc
Marcin Kiercak, Postdoc
Lina Hultin Rosenberg, Bioinformatician
Argyri “Iris” Mathioudaki, Graduate Student
Kate Megquier, Graduate student
Sharda Sakthikumar, Graduate student
Hanna Bremer, Graduate student
Eva Murén, Senior Research Engineer
Åsa Karlsson, Research Engineer

Key publications

  • Lindblad-Toh, K, et al. Genome Sequence, Comparative Analysis and haplotype structure of the domestic dog. (2005) Nature 438:803-819
  • Lindblad-Toh K, et al. (>80 authors) (2011) A high-resolution map of human evolutionary constraint using 29 mammals. Nature 478(7370):476-82
  • Wilbe M, Jokinen P, Truvé K, Seppala EH, Karlsson EK, Biagi T, Hughes A, Bannasch D, Andersson G, Hansson-Hamlin H, Lohi H & Lindblad-Toh K. (2010) Genome-wide association mapping identified multiple loci for a canine SLE-related disease complex Nat Genet. Mar;42(3):250-4.
  • Axelsson E, Ratnakumar A, Arendt ML, Maqbool K, Webster MT, Perloski M, Liberg O, Arnemo JM, Hedhammar A, Lindblad-Toh K (2013). The genomic signature of dog domestication reveals adaptation to a starch-rich diet. Nature. Jan 23. doi: 10.1038/nature11837
  • Amemiya CT, Alföldi J, et al, (>80 authors) Lindblad-Toh K. (2013) The African coelacanth genome provides insights into tetrapod evolution. Nature. Apr 18;496(7445):311-6. doi: 10.1038/nature12027

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