Peters Luanne L, Lambert Amy J, Zhang Weidong, Churchill Gary A, Brugnara Carlo, Platt Orah S
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA.
Mamm Genome. 2006 Apr;17(4):298-309. doi: 10.1007/s00335-005-0147-3. Epub 2006 Apr 4.
A substantial genetic contribution underlies variation in baseline peripheral blood counts. We performed quantitative trait locus/loci (QTL) analyses to identify chromosome (Chr) regions harboring genes influencing the baseline erythroid parameters in F2 intercrosses between NZW/LacJ, SM/J, and C57BLKS/J inbred mice. We identified multiple significant QTL for red blood cell (RBC) count, hemoglobin (Hgb) and hematocrit (Hct) levels, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean cell hemoglobin concentration (CHCM). We identified four RBC count QTL: Rbcq1 (Chr 1, peak LOD score at 62 cM,), Rbcq2 (Chr 4, 60 cM), Rbcq3 (Chr 11, 34 cM), and Rbcq4 (Chr 10, 60 cM). Three MCV QTL were identified: Mcvq1 (Chr 7, 30 cM), Mvcq2 (Chr 11, 6 cM), and Mcvq3 (Chr 10, 60 cM). Single significant loci for Hgb (Hgbq1, Chr 16, 32 cM), Hct (Hctq1, Chr 3, 42 cM), and MCH (Mchq1, Chr 10, 60 cM) were identified. The data support the existence of a common RBC/MCH/MCV locus on Chr 10. Two QTL for CHCM (Chcmq1, Chr 2, 48 cM; Chcmq2, Chr 9, 44 cM) and an interaction between Chcmq2 with a locus on Chr 19 were identified. These analyses emphasize the genetic complexity underlying the regulation of erythroid peripheral blood traits in normal populations and suggest that genes not previously recognized as significantly impacting normal erythropoiesis exist.
基线外周血细胞计数的变异有很大的遗传因素。我们进行了数量性状基因座(QTL)分析,以确定在NZW/LacJ、SM/J和C57BLKS/J近交系小鼠的F2杂交后代中,含有影响基线红细胞参数基因的染色体(Chr)区域。我们鉴定出了多个与红细胞(RBC)计数、血红蛋白(Hgb)和血细胞比容(Hct)水平、平均红细胞体积(MCV)、平均红细胞血红蛋白含量(MCH)以及平均红细胞血红蛋白浓度(CHCM)相关的显著QTL。我们鉴定出四个RBC计数QTL:Rbcq1(Chr 1,峰值LOD分数在62 cM处)、Rbcq2(Chr 4,60 cM)、Rbcq3(Chr 11,34 cM)和Rbcq4(Chr 10,60 cM)。鉴定出三个MCV QTL:Mcvq1(Chr 7,30 cM)、Mvcq2(Chr 11,6 cM)和Mcvq3(Chr 10,60 cM)。鉴定出了与Hgb(Hgbq1,Chr 16,32 cM)、Hct(Hctq1,Chr 3,42 cM)和MCH(Mchq1,Chr 10,60 cM)相关的单个显著基因座。数据支持在Chr 10上存在一个共同的RBC/MCH/MCV基因座。鉴定出两个与CHCM相关的QTL(Chcmq1,Chr 2,48 cM;Chcmq2,Chr 9,44 cM)以及Chcmq2与Chr 19上一个基因座之间的相互作用。这些分析强调了正常人群中红细胞外周血性状调控背后的遗传复杂性,并表明存在以前未被认为对正常红细胞生成有显著影响的基因。