Sequence assembly and annotation of the bovine major histocompatibility complex (BoLA) class IIb region, and in silico detection of sequence polymorphisms in BoLA IIb

摘要

Cattle are vitally important to American agriculture industry, generating over 24.6billion pounds of beef (by carcass weight), and 79.5 billion dollars in 2005, and over 27billion dollars in milk sales in 2004. As of July 2006, the U.S. beef and dairy industry iscomprised of 104.5 million head of cattle, 32.4 million of which were processed in 2005.The health of the animals has always been an important concern for breeders, as healthyanimals grow faster and are more likely to reach market weight. Animals that exhibitnatural resistance to disease do not require chemicals to stimulate normal weight gain,and are less prone to disease related wasting.The major histocompatibility complex (MHC) is a collection of genes, many ofwhich function in antigen processing and presentation. The bovine MHC (BoLA) differsfrom typical mammalian MHCs in that the class II region was disrupted by achromosomal inversion into two subregions, designated BoLA IIa and BoLA IIb. BoLAIIb was transposed to a position near the centromere on bovine chromosome 23,whileBoLA IIa retains its position in BoLA. Comparative sequence analysis of BoLA IIb withthe human MHC revealed the location of the region containing the proximal inversion breakpoint. Gene content, order and orientation of BoLA IIb are consistent with the singleinversion hypothesis when compared to the corresponding region of the human class IIMHC (HLA class II). BoLA IIb spans approximately 450 kb.The genomic sequence of BoLA IIb was used to detect sequence variationthrough comparison to other bovine sequences, including data from the bovine genomeproject, and two regions in the BAC scaffold used to develop the BoLA IIb sequence.Analysis of the bovine genome project sequence revealed a total of 10,408 mismatchingbases, 30 out of 231 polymorphic microsatellites, and 15 sequences corresponding to thevalidated SNP panel generated by the bovine genome sequencing project. The twooverlapping regions in the BoLA IIb BAC scaffold were found to have 888polymorphisms, including a total of 6 out of 42 polymorphic microsatellites indicatingthat each BAC derived from a different chromosome.