Mahaney Michael C, Brugnara Carlo, Lease Loren R, Platt Orah S
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX, USA.
Blood. 2005 Aug 15;106(4):1210-4. doi: 10.1182/blood-2004-12-4863. Epub 2005 May 3.
Interperson differences in peripheral blood cell counts in healthy individuals result from genetic and environmental influences. We used multivariate genetic analyses to assess the relative impact of genes and environment on baseline blood cell counts and indices using a pedigreed colony of baboons, an animal with well-documented analogies to human blood physiology. After accounting for age, sex, and weight, we found that genetic influences explain a significant proportion of the remaining variability, ranging from a low of 13.7% for mean corpuscular hemoglobin concentration (MCHC) to a high of 72.4% for red blood cell (RBC) number. Genes influence 38.5% of the variation in baseline white blood cell (WBC) count, a characteristic that correlates with mortality in both the general human population and clinically defined subgroups such as individuals with sickle-cell disease. We examined the interaction between pairs of traits and identified those that share common genetic influences (pleiotropy). We unexpectedly observed that the same gene or group of genes influences both WBC count and mean platelet volume (MPV). We anticipate that this approach will ultimately lead to discovery of novel insights into the biology of related traits, and ultimately identify important genes that affect hematopoiesis.
健康个体外周血细胞计数的个体差异源于遗传和环境影响。我们使用多变量遗传分析,利用一个狒狒谱系群体来评估基因和环境对基线血细胞计数及指标的相对影响,狒狒是一种在血液生理学方面与人类有充分记录的相似之处的动物。在考虑年龄、性别和体重因素后,我们发现遗传影响解释了剩余变异性的很大一部分,范围从平均红细胞血红蛋白浓度(MCHC)的低至13.7%到红细胞(RBC)数量的高至72.4%。基因影响基线白细胞(WBC)计数变异的38.5%,这一特征在普通人群和临床定义的亚组(如镰状细胞病患者)中均与死亡率相关。我们研究了成对性状之间的相互作用,并确定了那些共享共同遗传影响(多效性)的性状。我们意外地观察到,同一基因或一组基因同时影响白细胞计数和平均血小板体积(MPV)。我们预计这种方法最终将带来对相关性状生物学的新见解,并最终确定影响造血的重要基因。