GENETIC-BASIS OF NEURAL-TUBE DEFECTS - THE MOUSE GENE LOOP-TAIL MAPS TO A REGION OF CHROMOSOME-1 SYNTENIC WITH HUMAN 1Q21-Q23

A genetic basis for neural tube defects (NTD) is rarely doubted, but t he genes involved have not yet been identified. This is partly due to a lack of suitable families on which to perform linkage analysis. An a lternative approach is to use the many mouse genes that cause NTD as a means of isolating their human homologues. Loop-tail (Lp) is a semido minant mouse gene that, in homozygous mutants, causes the severe NTD p henotype cranio-rachischisis. As a first step toward cloning Lp, we ha ve performed linkage analysis on an intraspecific backcross, using mic rosatellite and RFLP DNA markers. This study has localized Lp to a reg ion of approximately 1.46 cM on mouse chromosome 1, flanked by the gen e for the alpha chain of high-affinity Fc receptor for IgE (Fcer1 alph a) and a microsatellite repeat D1Mit113. Physical mapping data in the region suggest that the interval is likely to be no more than 1.8 Mb i n size. The localization is several centimorgans distal to that previo usly assigned by linkage studies with biochemical and visible markers and suggests that the human homologue of Lp is likely to reside in a r egion of conserved homology on 1q21-q23. (C) 1995 Academic Press, Inc.