title: Cloning, expression and genomic structure of human LMX1A, and variant screening in Pima Indians.
abstract: LIM-homeodomain containing protein LMX1A activates transcription of the insulin gene. The human LMX1A gene maps to 1q22-q23, a region identified as a putative type 2 diabetes mellitus (T2DM) locus in several different populations. We analyzed LMX1A as a positional and biological candidate gene for T2DM in the Pima Indians, in whom a linkage of T2DM to 1q21-q23 has been previously reported. In the present study, we describe the cloning, expression and genomic organization of the LMX1A gene, which is composed of 11 exons spanning approximately 151 kb. In addition to a transcript encoding the predicted full-length protein of 382 amino acids, we identified two truncated cDNA forms produced via additional transcription start sites and alternative splicing. We identified seven single nucleotide polymorphisms (SNPs) throughout the LMX1A locus and determined allele frequency distributions in 150 diabetic and 150 unaffected Pimas. We did not find evidence for association of any LMX1A SNPs with T2DM and conclude that LMX1A does not contribute significantly to T2DM etiology in Pima Indians.
authors.affiliation: Clinical Diabetes and Nutrition Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ 85016, USA. fthameem@mail.nih.gov
authors.forename: Farook
authors.initials: F
authors.lastname: Thameem
authors.forename: Johanna K
authors.initials: JK
authors.lastname: Wolford
authors.forename: Juehu
authors.initials: J
authors.lastname: Wang
authors.forename: Michael S
authors.initials: MS
authors.lastname: German
authors.forename: Clifton
authors.initials: C
authors.lastname: Bogardus
authors.forename: Michal
authors.initials: M
authors.lastname: Prochazka
mesh_terms: D000483:Alleles; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000737:chemistry / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000517:prevention & control; D005091:Exons; D015870:Gene Expression; D005787:Gene Frequency; D005796:Genes / Q000235:genetics; D005820:Genetic Testing; D014644:Genetic Variation; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D007438:Introns; D060850:LIM-Homeodomain Proteins; D008297:Male; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D014157:Transcription Factors
chemical_list: D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C078021:LMX1A protein, human; D014157:Transcription Factors; D004247:DNA