Complete mutation analysis panel of the 39 human HOX genes.
BACKGROUND
The HOX gene family consists of highly conserved transcription factors that specify the identity of the body segments along the anteroposterior axis of the embryo. Because the phenotypes of mice with targeted disruptions of Hox genes resemble some patterns of human malformations, mutations in HOX genes have been expected to be associated with a significant number of human malformations. Thus far, however, mutations have been documented in only three of the 39 human HOX genes (HOXD13, HOXA13, and HOXA11) partly because current knowledge on the complete coding sequence and genome structure is limited to only 20 of the 39 human HOX genes.


METHODS
Taking advantage of the human and mouse draft genome sequences, we attempted to characterize the remaining 19 human HOX genes by bioinformatic analysis including phylogenetic footprinting, the probabilistic prediction method, and comparison of genomic sequences with the complete set of the human anonymous cDNA sequences.


RESULTS
We were able to determine the full coding sequences of 19 HOX genes and their genome structure and successfully designed a complete set of PCR primers to amplify the entire coding region of each of the 39 HOX genes from genomic DNA.


CONCLUSIONS
Our results indicate the usefulness of bioinformatic analysis of the draft genome sequences for clinically oriented research projects. It is hoped that the mutation panel provided here will serve as a launchpad for a new discourse on the genetic basis of human malformations.
Kosaki
Kenjiro
K
Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan. kkosaki@sc.itc.keio.ac.jp
Kosaki
Rika
R
Suzuki
Taichi
T
Yoshihashi
Hiroshi
H
Takahashi
Takao
T
Sasaki
Katsumi
K
Tomita
Masaru
M
McGinnis
William
W
Matsuo
Nobutake
N
D000818:Animals; D019295:Computational Biology; D003198:Computer Simulation; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D005801:Genes, Homeobox; D006801:Humans; D051379:Mice; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D016415:Sequence Alignment