ORIGINAL ARTICLE Fine mapping of quantitative trait loci affecting organ weights by mouse intersubspecific subcongenic strain analysis Md. Bazlur Rahman MOLLAH and Akira ISHIKAWA Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan ABSTRACT The genetic architecture of organ weights is not well understood. In this study, we fine-mapped quantitative trait loci (QTLs) affecting organ weights by characterizing six intersubspecific subcongenic mouse strains with overlapping and non- overlapping genomic regions on chromosome 2 derived from wild Mus musculus castaneus. QTLs for heart, lung, spleen and kidney weights were revealed on a 6.38-Mb genomic region between two microsatellite markers, D2Mit323 and D2Mit472. Effects of the castaneus alleles at the organ weight QTLs were all opposite in direction to a body weight QTL previously mapped to the same genomic region. In addition, new QTLs for lung and kidney weights were revealed on a different 3.57-Mb region between D2Mit205 and D2Mit182. Their effects were dependent on that of another body weight QTL previously mapped to that genomic region. The organ weight QTLs revealed were all duplicated in independent analyses with F2 intercross populations between subcongenic strains carrying these QTLs and their background strain. The findings suggested that organ weights are not exclusively regulated by genetic loci that commonly influence overall body weight and rather that there are loci contributing to the growth of specific organs only. Key words: congenic strain, organ weight, QTL, subcongenic strain, wild mice. INTRODUCTION In recent years, the development of abundant poly- morphic molecular markers in different organisms and the development of sophisticated statistical methods have paved the way for studying the genetic architec- ture of body weight and growth by identification of quantitative trait loci (QTLs) affecting them. Body weight in mice has been studied in detail and many QTLs have been mapped to chromosomal regions as reviewed elsewhere (Wuschke et al. 2007). Body weight is a composite of fat mass, internal organ mass, muscle mass and skeleton mass. Each of these body composition traits has different developmental proce- dures and growth rates during postnatal growth (Law- rence & Fowler 2002). However, the genetic architecture of specific body composition traits has not been studied in as much detail as that of overall body weight (Leamy et al. 2002; Kenney-Hunt et al. 2006; Neuschl et al. 2007). Congenic strains in rodents are one of the common and useful genomic resources for studying complex traits. They possess a differential chromosomal segment from a donor strain, which is transferred through recurrent backcrossing to the background of a recipient strain (Silver 1995). Correspondingly, sub- congenic strains are derived from a congenic and possess a smaller portion of the original donor segment. Subcongenics are created using recom- binants isolated from an intercross or backcross between the original congenic and its recipient strain. QTLs are usually isolated using a set of overlapping and/or nonoverlapping subcongenics that span the entire donor region. Subcongenic fine mapping has successfully narrowed QTLs for many traits such as obesity (Diament & Warden 2004; Mizutani et al. 2006), atherosclerosis susceptibility (Wang et al. 2005; Ghazalpour et al. 2006), diabetes (Serreze et al. 1998; Lyons et al. 2000; Pomerleau et al. 2005; Clee et al. 2006) and bone mineral density (Edderkaoui et al. 2006), and the number is increasing day by day. Some Correspondence: Akira Ishikawa, Laboratory of Animal Genetics, Division of Applied Genetics and Physiology, Graduate School of Bioagricultural Sciences, Nagoya Univer- sity, Chikusa, Nagoya 464-8601, Japan. (Email: ishikawa@ agr.nagoya-u.ac.jp) Received 1 March 2012; accepted for publication 20 July 2012. Animal Science Journal (2013) 84, 296–302 doi: 10.1111/asj.12004 © 2012 Japanese Society of Animal Science