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

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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.