Genetic background of dwarfism in the Friesian horse

Abstract

Research goal: The gene responsible for dwarfism is located near the terminal end of the short arm of chromosome 14. Goal is to 1) finemap the region of association with newly recruited cases and controls, 2) develop and validate a DNA test and 3) analyze FGFR4 as candidate gene. Material and methods: DNA and RNA analysis of recently recruited dwarfs. Genotyping SNP markers on ECA14 using DNA sequencing. Selecting informative SNPs for RFLP assay and validate this DNA test in a larger group. FGFR4: characterizing exons and mutation detection using DNA and RNA sequence analysis. Results: The region of association on chromosome 14 is bordered by BIEC2-238965 and BIEC2-239795. SNPs in between are associated with dwarfism, with BIEC2-239391 and BIEC2-239646 most significantly associated. It could not be confirmed that a mutation in FGFR4 is represented in the coding sequence of the mRNA. Conclusion: The region of association is bordered by BIEC2-238965 and BIEC2-239795. Some controls had the dwarfism genotype for all SNPs except BIEC2-239391 and BIEC2-239646. Therefore, BIEC2-239391 and BIEC2-239646 are the most interesting for further research. The SNP in FGFR4 is unlikely to be a coding SNP. It is not well preserved and it could not be sequenced in cDNA. This could be due to the primers or steps in the protocols and therefore further investigation is needed to confirm this finding. It is also unlikely that there is an 18th exon in the horse. Next Generation sequencing will be performed on in a short period of time and its results should be used to identify and/or confirm candidate genes and mutations.