IDENTIFICATION OF A HUMAN LRMX1 (LMX1.1)-RELATED GENE, LMX1.2 - TISSUE-SPECIFIC EXPRESSION AND LINKAGE MAPPING ON CHROMOSOME-9

LMX1 is a LIM-homeodomain (LIM-HD)-containing protein expressed select ively in insulin-producing beta-cell lines, and it it has been shown t o activate insulin gene transcription. The human LMX1 gene was mapped by fluorescence in situ hybridization to chromosome region 1q22-q23, y et Church et al. (1994, Nat. Genet. 6: 98-105) identified two exon-tra pping products from human chromosome 9 that were highly homologous to hamster LMX1. In the current study, we demonstrate tissue-specific exp ression of an LMX1 (now known as LMX1.1)-related gene, named LMX1.2. T he chicken C-LMX1 gene, recently cloned using the hamster LMX1.1 seque nce and shown to specify dorsal cell fate during vertebrate limb devel opment (9), is actually more related to human LMX1.1 than LMX1.1. We h ave identified a unique simple sequence repeat polymorphic marker (hLM X1.2CA1) in a P1 genomic clone containing the human LMX1.2 gene and ge netically mapped the marker on chromosome 9 between markers D9S1825 an d D9S290 with odds of at least 1000:1. In addition, we localized the h uman LMX1.1 gene to three CEPH ''B'' yeast artificial chromosome clone s (907A11, 935B12, and 947B2), along with two nearby polymorphic marke rs (D1S426 and D1S194)). Identification of this new LIM-HD-related gen e may provide the opportunity to elucidate further the function of LIM class homeobox genes. Nearby polymorphic markers will be useful in te sting the hypothesis that mutations in these LIM-HD genes result in ge netic diseases such as non-insulin-dependent diabetes mellitus. (C) 19 97 Academic Press.