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）的基因组结构：人类基因组测序中心公布了牛全基因组草图序列，该信息已在NCBI基因组计划数据库（http：//www.ncbi.nlm.nih.gov/）中获得。本文利用BoLA基因草图序列和人类MHC基因全序列，对人类6号染色体上的MHC区域（HSP 6p）和23号染色体上的BoLA区域（BTA 23）进行了比较分析。虽然牛基因图谱中存在两个II类亚区（参见IIa类和IIb类），并在我们基于全基因组草图测序的比较基因图谱中得到证实，一些新构建的基因对应关系显示出与以前连锁图谱的差异。BoLA IIa类区域与乳腺炎和牛白血病病毒（BLV）诱导的淋巴瘤发生的关系：BoLA IIa类区域显示与各种疾病和经济性状相关。IIa类基因区含有BoLA-DRB、-DQA和-DQB基因，具有高度的多态性。最近，我们开发了新的基于序列的分型（SBT）方法，该方法允许鉴定大量具有相关病例的动物的BoLA-DQA 1基因和BoLA-DRB 3基因的等位基因，并且显示DRB 3 ^*0701-DQA 1 ^*0101和DRB 3 ^*14012-DQA 1 ^*10012可能防止BLV诱导的淋巴瘤的发展。我们现在的进展是鉴定与这两个等位基因相关的BLV表位。其次，我们对188头乳腺炎牛和95头正常荷斯坦牛的DQA 1等位基因进行了分型，并计算了两组中每个等位基因的频率。DQA 1 ^*1201等位基因在乳腺炎组中的频率明显低于正常组（p=0.006663），提示该等位基因可能与乳腺炎抗性呈正相关。因此，利用BoLA Ⅱ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.