title: Genetic mapping of the human homologue (T) of mouse T(Brachyury) and a search for allele association between human T and spina bifida.
abstract: We describe a genetic analysis of the human homologue (T) of the mouse T (Brachyury) gene; human T was recently cloned in our laboratory. The protein product of the T gene is a transcription factor crucial in vertebrates for the formation of normal mesoderm. T mutant Brachyury mice die in midgestation with severe defects in posterior mesodermal tissues; heterozygous mice are viable but have posterior axial malformations. In addition to its importance in development, T has intrigued geneticists because of its association with the mouse t-haplotype; this haplotype is a variant form of the t-complex and is characterized by transmission ratio distortion, male sterility and recombination suppression. We have identified a common polymorphism of human T by single strand conformation polymorphism (SSCP) and used this in mapping studies and to re-investigate the idea that human T is involved in susceptibility to the multifactorial, neural tube defect, spina bifida. Our mapping data show that human T maps to 6q27 and lies between two other genes of the t-complex, TCP1 and TCP10. These data add to the evidence that in man the genes of the t-complex are split into two main locations on the short and long arms of chromosome 6. We have used an allele association test which is independent of mode of inheritance and penetrance to analyse data from the spina bifida families. Using this test we find evidence for a significant (p = 0.02) association between transmission of the TIVS7-2 allele of the human T gene and spina bifida.
authors: MRC Human Biochemical Genetics Unit, University College London, UK.
authors: K
authors: K
authors: Morrison
authors: C
authors: C
authors: Papapetrou
authors: J
authors: J
authors: Attwood
authors: F
authors: F
authors: Hol
authors: S A
authors: SA
authors: Lynch
authors: A
authors: A
authors: Sampath
authors: B
authors: B
authors: Hamel
authors: J
authors: J
authors: Burn
authors: J
authors: J
authors: Sowden
authors: D
authors: D
authors: Stott
authors: E
authors: E
authors: Mariman
authors: Y H
authors: YH
authors: Edwards
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005326:Fetal Proteins / Q000235:genetics*; D008040:Genetic Linkage; D006720:Homozygote; D006801:Humans; D007438:Introns; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D016135:Spinal Dysraphism / Q000235:genetics*; D020825:T-Box Domain Proteins; D014157:Transcription Factors / Q000235:genetics*; D000098908:Brachyury Protein
chemical_list: D004268:DNA-Binding Proteins; D005326:Fetal Proteins; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D000098908:Brachyury Protein