Genome analysis of bovine major histocompatibility complex region and development of cattle with resistance to disease

牛主要组织相容性复合体（BoLA）的基因组组织：人类基因组测序中心已经公布了牛全基因组的草图序列，并已在NCBI基因组计划数据库（http://www.ncbi.nlm.nih.gov/）中查询。本文利用BoLA草图序列和人类MHC区域完整序列，分析了人类6号染色体MHC区域（HSP6p）和23号染色体BoLA区域（BTA23）的对比图谱。虽然牛基因图谱中存在两个II类亚区（参见IIa类和IIb类），并且在我们基于全基因组草图测序的比较基因图谱中也得到了证实，但一些新构建的基因对应关系与之前的连锁图谱存在差异。BoLA IIa区与乳腺炎和牛白血病病毒（BLV）诱导淋巴瘤发生的关系：发现BoLA IIa区与多种疾病和经济性状相关。IIa类区域包含BoLA-DRA、-DRB、-DQA和-DQB基因，多态性程度较高。近年来，我们建立了基于序列分型（SBT）的新方法，对大量相对病例动物的BoLA-DQA1基因和BoLA-DRB3基因等位基因进行了鉴定，结果表明DRB3^*0701-DQA1^*0101和DRB3^*14012-DQA1^*10012可能对blv诱导淋巴瘤的发生具有保护作用。目前，我们正在进一步确定与这两个等位基因相关的BLV表位。接下来，我们对188头乳腺炎牛和95头正常荷斯坦牛的DQA1等位基因进行分型，并计算两组中每个等位基因的频率。DQA1^*1201等位基因在乳腺炎组明显低于正常组（p=0.006663），提示该等位基因可能与乳腺炎耐药呈正相关。综上所述，利用BoLAⅱ类单倍型进行标记选择育种，可能有助于提高家牛的抗病性状。

Genomic organization of bovine major histocompatibility complex (BoLA) : The draft sequence of entire bovine genome has been announced by Human Genome Sequencing Center, and the information has been available in NCBI genome project database (http://www.ncbi.nlm.nih.gov/). Here, we analyzed the comparative map of human MHC region on chromosome 6 (HSP6p) and BoLA region on chromosome 23 (BTA23), using the draft sequence of BoLA and complete sequence of human MHC region. Although the existence of two class II subregions in cattle gene map was known before (cf.class IIa and IIb), and is also confirmed in our comparative gene map based on the whole genome draft sequencing, some of the newly constructed gene correspondences show differences from the previous linkage map.Relationship between BoLA class IIa region and development of mastitis and bovine leukemia virus (BLV)-induced lymphoma : BoLA class IIa region revealed to associate in various diseases and economic trait. The class IIa region contains BoLA-DRA, -DRB, -DQA and -DQB genes and shows a high degree of polymorphism. Recently, we developed new methods for sequence based typing (SBT) which allow identification of alleles of BoLA-DQA1 gene and BoLA-DRB3 gene of large numbers of animals with relative case, and showed that the DRB3^*0701-DQA1^*0101 and DRB3^*14012-DQA1^*10012 might protect against development of BLV-induced lymphoma. We now progress to identify BLV epitope which related to both alleles. Next, we performed the typing of DQA1 alleles of 188 cattle with mastitis and 95 normal Holstein cattle and calculated each allele frequency in two groups. The DQA1^*1201 were apparently low frequency in mastitis group as compared with a normal group (p=0.006663), suggesting that this allele might be positively related to resistance to mastitis. Collectively, the breeding by the marker selection using BoLA class II haplotype might probably contribute to the improvement of disease resistance traits in domestic cattle.