PHYSICAL MAPPING OF THE HOLOPROSENCEPHALY CRITICAL REGION IN 21Q22.3,EXCLUSION OF SIM2 AS A CANDIDATE GENE FOR HOLOPROSENCEPHALY, AND MAPPING OF SIM2 TO A REGION OF CHROMOSOME-21 IMPORTANT FOR DOWN-SYNDROME

We set out to define the holoprosencephaly (HPE) critical region on ch romosome 21 and also to determine whether there were human homologues of the Drosophila single-minded (sim) gene that might be involved in H PE. Analysis of somatic cell hybrid clones that contained rearranged c hromosomes 21 from HPE patients defined the HPE minimal critical regio n in 21q22.3 as D21S113 to qter. We used established somatic cell hybr id mapping panels to map SIM2 to chromosome 21 within subbands q22.2-q 22.3. Analysis of the HPE patient-derived somatic cell hybrids showed that SIM2 is not deleted in two of three patients and thus is not a li kely candidate for HPE1, the HPE gene on chromosome 21. However, SIM2 does map within the Down syndrome critical region and thus is a candid ate gene that might contribute to the Down syndrome phenotype.