Yu Hongrun, Edderkaoui Bouchra, Cortez Alejandro, Davidson Heather M, Wergedal Jon E, Baylink David J, Mohan Subburaman
Musculoskeletal Disease Center, Jerry L. Pettis Memorial VA Medical Center, Loma Linda, CA 92357, USA.
Genetica. 2009 Jan;135(1):59-66. doi: 10.1007/s10709-008-9258-6. Epub 2008 Mar 11.
Developing treatment strategies for osteoporosis would be facilitated by identifying genes regulating bone mineral density (BMD). One way to do so is through quantitative trait locus (QTL) mapping. However, there are sex differences in terms of the presence/absence and locations of BMD QTLs. In a previous study, our group identified a BMD QTL on chromosome 17 in the F(2) female mice of the MRL/MpJ x SJL/J cross. Here, we determined whether it was also present in the male mice of the same cross. Furthermore, we also intended to reduce the QTL region by increasing marker density. Interval mapping showed that the same QTL based on chromosomal positions was present in the male mice, with logarithmic odds (LOD) scores of 4.0 for femur BMD and 5.2 for total body BMD. Although there was a body weight QTL at the same location, the BMD QTL was not affected by the adjustment for body weight. Mapping with increased marker density indicated a most likely region of 35-55 Mb for this QTL. There were also co-localized QTLs for femur length, femur periosteal circumference (PC) and total body bone area, suggesting possibility of pleiotropy. Runx2 and VEGFA are strong candidate genes located within this QTL region.
确定调控骨密度(BMD)的基因将有助于制定骨质疏松症的治疗策略。一种方法是通过数量性状基因座(QTL)定位。然而,BMD QTL的存在与否及位置存在性别差异。在之前的一项研究中,我们的研究小组在MRL/MpJ×SJL/J杂交的F(2)雌性小鼠的17号染色体上鉴定出一个BMD QTL。在此,我们确定它是否也存在于同一杂交的雄性小鼠中。此外,我们还打算通过增加标记密度来缩小QTL区域。区间定位显示,基于染色体位置的相同QTL存在于雄性小鼠中,股骨BMD的对数优势(LOD)分数为4.0,全身BMD的LOD分数为5.2。尽管在同一位置存在体重QTL,但BMD QTL不受体重调整的影响。增加标记密度的定位表明该QTL最可能的区域为35-55 Mb。股骨长度、股骨骨膜周长(PC)和全身骨面积也存在共定位QTL,提示存在多效性的可能性。Runx2和VEGFA是位于该QTL区域内的强有力候选基因。