Fine mapping of a QTL for ear size on porcine chromosome 5 and identification of high mobility group AT-hook 2 (HMGA2) as a positional candidate gene

Four new markers on pig chromosome 5 were genotyped across this F2 population. RT-PCR was performed to obtain expression profiles of different candidate genes in ear tissue. Standard association test, marker-assisted association test and F-drop test were applied to determine the effects of single nucleotide polymorphisms (SNP) on ear size. Three synthetic commercial lines were also used for the association test.We refined the QTL to an 8.7-cM interval and identified three positional candidate genes i.e. HMGA2, SOX5 and PTHLH that are expressed in ear tissue. Seven SNP within these three candidate genes were selected and genotyped in the F2 population. Of the seven SNP, HMGA2 SNP (JF748727: g.2836 A > G) showed the strongest association with ear size in the standard association test and marker-assisted association test. With the F-drop test, F value decreased by more than 97% only when the genotypes of HMGA2 g.2836 A > G were included as a fixed effect. Furthermore, the significant association between g.2836 A > G and ear size was also demonstrated in the synthetic commercial Sutai pig line. The haplotype-based association test showed that the phenotypic variance explained by HMGA2 was similar to that explained by the QTL and at a much higher level than by SOX5. More interestingly, HMGA2 is also located within the dog orthologous chromosome region, which has been shown to be associated with ear type and size.HMGA2 was the closest gene with a potential functional effect to the QTL or marker for ear size on chromosome 5. This study will contribute to identify the causative gene and mutation underlying this QTL.Ear size and erectness are important conformation characteristics of pig breeds. Moreover, ear defects have been observed in different species [1,2]. For example, in humans, congenital underdevelopment of the external ear or microtia, affects about 1 in 6000 children in Europe and the USA, and 1 in 4000 in Japan and China [3]. Pig can be used as an animal model t