Evans David M, Zhu Gu, Duffy David L, Montgomery Grant W, Frazer Ian H, Martin Nicholas G
Queensland Institute of Medical Research and Joint Genetics Program, University of Queensland, Brisbane, Australia.
J Allergy Clin Immunol. 2004 Oct;114(4):826-30. doi: 10.1016/j.jaci.2004.05.060.
Eosinophils are granulocytic white blood cells implicated in asthma and atopic disease. The degree of eosinophilia in the blood of patients with asthma correlates with the severity of asthmatic symptoms. Quantitative trait loci (QTL) linkage analysis of eosinophil count may be a more powerful strategy of mapping genes involved in asthma than linkage analysis using affected relative pairs.
To identify QTLs responsible for variation in eosinophil count in adolescent twins.
We measured eosinophil count longitudinally in 738 pairs of twins at 12, 14, and 16 years of age. We typed 757 highly polymorphic microsatellite markers at an average spacing of approximately 5 centimorgans across the genome. We then used multipoint variance components linkage analysis to test for linkage between marker loci and eosinophil concentrations at each age across the genome.
We found highly significant linkage on chromosome 2q33 in 12-year-old twins (logarithm of the odds=4.6; P=.000002) and suggestive evidence of linkage in the same region in 14-year-olds (logarithm of the odds=1.0; P=.016). We also found suggestive evidence of linkage at other areas of the genome, including regions on chromosomes 2, 3, 4, 8, 9, 11, 12, 17, 20, and 22.
A QTL for eosinophil count is present on chromosome 2q33. This QTL might represent a gene involved in asthma pathophysiology.
嗜酸性粒细胞是与哮喘和特应性疾病相关的粒细胞性白细胞。哮喘患者血液中的嗜酸性粒细胞增多程度与哮喘症状的严重程度相关。与使用受累亲属对进行连锁分析相比，对嗜酸性粒细胞计数进行数量性状基因座（QTL）连锁分析可能是定位参与哮喘的基因的更有效策略。
鉴定导致青少年双胞胎嗜酸性粒细胞计数变异的QTL。
我们在738对双胞胎12、14和16岁时纵向测量了嗜酸性粒细胞计数。我们在全基因组中平均间隔约5厘摩的位置对757个高度多态性微卫星标记进行了分型。然后，我们使用多点方差成分连锁分析来测试全基因组中每个年龄的标记位点与嗜酸性粒细胞浓度之间的连锁关系。
我们在12岁双胞胎的2q33染色体上发现了高度显著的连锁（优势对数=4.6；P=0.000002），在14岁双胞胎的同一区域发现了连锁的提示性证据（优势对数=1.0；P=0.016）。我们还在基因组的其他区域发现了连锁的提示性证据，包括2、3、4、8、9、11、12、17、20和22号染色体上的区域。
2q33染色体上存在一个嗜酸性粒细胞计数的QTL。这个QTL可能代表一个参与哮喘病理生理学的基因。
