%0 Journal Article %J Anim Genet %D 2006 %T Comparative analysis of the bovine MHC class IIb sequence identifies inversion breakpoints and three unexpected genes. %A Childers, C P %A Newkirk, H L %A Honeycutt, D A %A Ramlachan, N %A Donna M Muzny %A Sodergren, E %A Richard A Gibbs %A Weinstock, G M %A Womack, J E %A Skow, L C %K Animals %K Cattle %K Chromosome Inversion %K Chromosomes, Mammalian %K Contig Mapping %K Evolution, Molecular %K Genes, MHC Class II %K Histones %K Humans %K Molecular Sequence Data %K Sequence Analysis, DNA %X

The bovine major histocompatibility complex (MHC) or BoLA is organized differently from typical mammalian MHCs in that a large portion of the class II region, called class IIb, has been transposed to a position near the centromere on bovine chromosome 23. Gene mapping indicated that the rearrangement resulted from a single inversion, but the boundaries and gene content of the inverted segment have not been fully determined. Here, we report the genomic sequence of BoLA IIb. Comparative sequence analysis with the human MHC revealed that the proximal inversion breakpoint occurred approximately 2.5 kb from the 3' end of the glutamate-cysteine ligase, catalytic subunit (GCLC) locus and that the distal breakpoint occurred about 2 kb from the 5' end from a divergent class IIDRbeta-like sequence designated DSB. Gene content, order and orientation of BoLA IIb are consistent with the single inversion hypothesis when compared with the corresponding region of the human class II MHC (HLA class II). Differences with HLA include the presence of a single histone H2B gene located between the proteasome subunit, beta type, 9 (PSMB9) and DMB loci and a duplicated TAP2 with a variant splice site. BoLA IIb spans approximately 450 kb DNA, with 20 apparently intact genes and no obvious pseudogenes. The region contains 227 simple sequence repeats (SSRs) and approximately 167 kb of retroviral-related repetitive DNA. Nineteen of the 20 genes identified in silico are supported by bovine EST data indicating that the functional gene content of BoLA IIb has not been diminished because it has been transposed from the remainder of BoLA genes.

%B Anim Genet %V 37 %P 121-9 %8 2006 Apr %G eng %N 2 %1 https://www.ncbi.nlm.nih.gov/pubmed/16573526?dopt=Abstract %R 10.1111/j.1365-2052.2005.01395.x %0 Journal Article %J Science %D 2004 %T In silico genetics: identification of a functional element regulating H2-Ealpha gene expression. %A Liao, Guochun %A Wang, Jianmei %A Guo, Jingshu %A Allard, John %A Cheng, Janet %A Ng, Anh %A Shafer, Steve %A Puech, Anne %A McPherson, John D %A Foernzler, Dorothee %A Peltz, Gary %A Usuka, Jonathan %K Alleles %K Animals %K Binding Sites %K Computational Biology %K Electrophoretic Mobility Shift Assay %K Gene Expression Profiling %K Gene Expression Regulation %K Genes, MHC Class II %K Genetic Variation %K H-2 Antigens %K Haplotypes %K Hydrocarbons, Aromatic %K Introns %K Liver %K Lung %K Major Histocompatibility Complex %K Mice %K Mice, Inbred Strains %K Oligodeoxyribonucleotides %K Oligonucleotide Array Sequence Analysis %K Phenotype %K Polymorphism, Single Nucleotide %K Receptors, Aryl Hydrocarbon %K Regulatory Sequences, Nucleic Acid %K Serum Response Factor %K Transcription Factors %X

Computational tools can markedly accelerate the rate at which murine genetic models can be analyzed. We developed a computational method for mapping phenotypic traits that vary among inbred strains onto haplotypic blocks. This method correctly predicted the genetic basis for strain-specific differences in several biologically important traits. It was also used to identify an allele-specific functional genomic element regulating H2-Ealpha gene expression. This functional element, which contained the binding sites for YY1 and a second transcription factor that is probably serum response factor, is located within the first intron of the H2-Ealpha gene. This computational method will greatly improve our ability to identify the genetic basis for a variety of phenotypic traits, ranging from qualitative trait information to quantitative gene expression data, which vary among inbred mouse strains.

%B Science %V 306 %P 690-5 %8 2004 Oct 22 %G eng %N 5696 %1 https://www.ncbi.nlm.nih.gov/pubmed/15499019?dopt=Abstract %R 10.1126/science.1100636