In silico genetics: identification of a functional element regulating H2-Ealpha gene expression.
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.
Liao
Guochun
G
Department of Genetics and Genomics, Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, CA 94304-1397, USA.
Wang
Jianmei
J
Guo
Jingshu
J
Allard
John
J
Cheng
Janet
J
Ng
Anh
A
Shafer
Steve
S
Puech
Anne
A
McPherson
John D
JD
Foernzler
Dorothee
D
Peltz
Gary
G
Usuka
Jonathan
J
D000483:Alleles; D000818:Animals; D001665:Binding Sites; D019295:Computational Biology; D024202:Electrophoretic Mobility Shift Assay; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II; D014644:Genetic Variation; D006183:H-2 Antigens / Q000235:genetics*; D006239:Haplotypes; D006841:Hydrocarbons, Aromatic / Q000494:pharmacology; D007438:Introns; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018336:Receptors, Aryl Hydrocarbon / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D026362:Serum Response Factor / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D006183:H-2 Antigens; D006841:Hydrocarbons, Aromatic; D009838:Oligodeoxyribonucleotides; D018336:Receptors, Aryl Hydrocarbon; D026362:Serum Response Factor; D014157:Transcription Factors