Department of Genetics, Smurfit Institute, Trinity College Dublin, Dublin, Ireland.
PLoS One. 2012;7(2):e30545. doi: 10.1371/journal.pone.0030545. Epub 2012 Feb 15.
Bovine tuberculosis is a significant veterinary and financial problem in many parts of the world. Although many factors influence infection and progression of the disease, there is a host genetic component and dissection of this may enlighten on the wider biology of host response to tuberculosis. However, a binary phenotype of presence/absence of infection presents a noisy signal for genomewide association study.
METHODOLOGY/PRINCIPAL FINDINGS: We calculated a composite phenotype of genetic merit for TB susceptibility based on disease incidence in daughters of elite sires used for artificial insemination in the Irish dairy herd. This robust measure was compared with 44,426 SNP genotypes in the most informative 307 subjects in a genome wide association analysis. Three SNPs in a 65 kb genomic region on BTA 22 were associated (i.e. p<10(-5), peaking at position 59588069, p = 4.02×10(-6)) with tuberculosis susceptibility.
CONCLUSIONS/SIGNIFICANCE: A genomic region on BTA 22 was suggestively associated with tuberculosis susceptibility; it contains the taurine transporter gene SLC6A6, or TauT, which is known to function in the immune system but has not previously been investigated for its role in tuberculosis infection.
牛结核病是世界许多地区重要的兽医和经济问题。尽管许多因素影响疾病的感染和进展，但存在宿主遗传成分，对其进行剖析可能有助于了解宿主对结核病反应的更广泛生物学。然而，感染存在/不存在的二元表型为全基因组关联研究提供了一个嘈杂的信号。
方法/主要发现：我们根据用于爱尔兰奶牛群人工授精的优秀种公牛的女儿的疾病发病率，计算了对结核病易感性的遗传优势综合表型。将这一稳健的衡量标准与最具信息量的 307 个受试者中的 44426 个 SNP 基因型进行了比较。在全基因组关联分析中，在 BTA22 上的 65kb 基因组区域的三个 SNP 与结核病易感性相关（即 p<10(-5)，峰值位于位置 59588069，p=4.02×10(-6)）。
结论/意义：BTA22 上的一个基因组区域与结核病易感性呈暗示性相关；它包含牛磺酸转运蛋白基因 SLC6A6，或 TauT，已知其在免疫系统中发挥作用，但以前尚未研究其在结核病感染中的作用。
