In silico genetics: identification of a functional element regulating H2-Ealpha gene expression

Science. 2004 Oct 22;306(5696):690-5. doi: 10.1126/science.1100636.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Animals
  • Binding Sites
  • Computational Biology*
  • Electrophoretic Mobility Shift Assay
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Genes, MHC Class II
  • Genetic Variation
  • H-2 Antigens / genetics*
  • Haplotypes
  • Hydrocarbons, Aromatic / pharmacology
  • Introns
  • Liver / metabolism
  • Lung / metabolism
  • Major Histocompatibility Complex
  • Mice
  • Mice, Inbred Strains
  • Oligodeoxyribonucleotides / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Receptors, Aryl Hydrocarbon / chemistry
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism
  • Regulatory Sequences, Nucleic Acid
  • Serum Response Factor / metabolism
  • Transcription Factors / metabolism

Substances

  • H-2 Antigens
  • Hydrocarbons, Aromatic
  • Oligodeoxyribonucleotides
  • Receptors, Aryl Hydrocarbon
  • Serum Response Factor
  • Transcription Factors