Cloning, genomic structure, and expression profiles of TULIP1 (GARNL1), a brain-expressed candidate gene for 14q13-linked neurological phenotypes, and its murine homologue

Genomics. 2004 Sep;84(3):577-86. doi: 10.1016/j.ygeno.2004.04.013.

Abstract

Previously, we have described the clinical and molecular characterization of a de novo 14q13.1-q21.1 microdeletion, less than 3.5 Mb in size, in a patient with severe microcephaly, psychomotor retardation, and other clinical anomalies. Here we report the characterization of the genomic structure of the human tuberin-like protein gene 1 (TULIP1; approved gene symbol GARNL1), a CpGisland-associated, brain-expressed candidate gene for the neurological findings in our patient, and its murine homologue. The human TULIP1 gene was mapped to chromosome band 14q13.2 by fluorescence in situ hybridization of BAC clone RP11-355C3 (GenBank Accession No. AL160231), containing the 3' region of the gene. TULIP1 spans about 271 kb of human genomic DNA and is divided into 41 exons. An untranscribed, processed pseudogene of TULIP1 was found on human chromosome band 9q31.1. The active locus TULIP1, encoding a predicted protein of 2036 amino acids, is expressed ubiquitously in pre- and postnatal human tissues. The murine homologue Tulip1 spans about 220 kb of mouse genomic DNA and is also divided into 41 exons, encoding a predicted protein of 2035 amino acids. No pseudogene could be found in the available mouse sequence data. Several splicing variants were found. Considering the location, expression profile, and predicted function, TULIP1 is a strong candidate for several neurological features seen in 14q deletion patients. Additionally we searched for mutations in the coding region of TULIP1 in subjects from a family with idiopathic basal ganglia calcification (IBGC; Fahr disease), previously linked to chromosome 14q. We identified two novel SNPs in the intron-exon boundaries; however, they did not segregate only with affected subjects in the predicted model of an autosomal dominant disease such as IBGC.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Northern
  • Chromosome Mapping
  • Chromosomes, Human, Pair 14 / genetics*
  • DNA Primers
  • Evolution, Molecular
  • GTPase-Activating Proteins / genetics*
  • GTPase-Activating Proteins / metabolism
  • Gene Components
  • Gene Expression Profiling*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Mice / genetics*
  • Molecular Sequence Data
  • Mutation / genetics
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Nervous System Diseases / genetics*
  • Phenotype*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Species Specificity

Substances

  • DNA Primers
  • GTPase-Activating Proteins
  • Nerve Tissue Proteins
  • RALGAPA1 protein, human

Associated data

  • GENBANK/AL160231