Genetic Mapping of the Human Homologue (T) of Mouse T(Brachyury) and a Search for Allele Association between Human T and Spina Bifida

• Published in: Human molecular genetics 1996-05, Vol.5 (5), p.669-674
• Main Authors: Morrison, Katie, Papapetrou, Charalambos, Attwood, John, Hol, Frans, Lynch, Sally A., Sampath, Anu, Hamel, Ben, Burn, John, Sowden, Jane, Stott, David, Mariman, Edwin, Edwards, Yvonne H.
• Format: Article
• Language: English
• Subjects: Alleles; Animals; Base Sequence; Biological and medical sciences; Chromosome Mapping; Chromosomes, Human, Pair 6; Diseases of the osteoarticular system; DNA-Binding Proteins - genetics; Female; Fetal Proteins - genetics; Genetic Linkage; Homozygote; Humans; Introns; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical sciences; Mice; Molecular Sequence Data; Polymorphism, Genetic; Polymorphism, Single-Stranded Conformational; Spinal Dysraphism - genetics; T-Box Domain Proteins; Transcription Factors - genetics
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/5.5.669

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 Brachyurymice 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, Thas 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 Tby 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-com-plex 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 Tgene and spina bifida.