title: Genomic organization of the human galpha14 and Galphaq genes and mutation analysis in chorea-acanthocytosis (CHAC).
abstract: Chorea-acanthocytosis (CHAC) (OMIM 200150) is a rare neurological syndrome characterized by neurodegeneration in combination with morphologically abnormal red cells (acanthocytosis). A partial yeast artificial chromosome contig of the CHAC critical region on chromosome 9q21 has been constructed, and 21 expressed sequence tags have been mapped. We have subsequently cloned Galpha14, a member of the G-protein alpha-subunit multigene family, and have identified Galphaq in the contig. The genomic structure of both genes has been established after construction of a bacterial artificial chromosome contig that showed Galphaq and Galpha14 to be in a head-to-tail arrangement (Cen-Galphaq-Galpha14-qter). Northern analysis found Galphaq to be ubiquitously expressed and Galpha14 to display a more restricted pattern of expression. Mutation analysis of the coding regions and splice sites for Galphaq and Galpha14 in 10 affected individuals from different families identified no changes likely to cause disease; however, two distinct single nucleotide polymorphisms in the coding region of Galpha14 have been identified. This study has excluded two plausible candidate genes from involvement in CHAC and has provided a solid platform for a positional cloning initiative.
authors: The Wellcome Trust Centre for Human Genetics, Windmill Road, Headington, OX3 7BN, England.
authors: J P
authors: JP
authors: Rubio
authors: E R
authors: ER
authors: Levy
authors: C
authors: C
authors: Dobson-Stone
authors: A P
authors: AP
authors: Monaco
mesh_terms: D000050:Acanthocytes; D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002819:Chorea / Q000235:genetics*; D018244:Chromosomes, Artificial, Yeast; D004252:DNA Mutational Analysis; D017931:DNA Primers; D018900:Dinucleotide Repeats; D016521:Electrophoresis, Gel, Pulsed-Field; D005091:Exons; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019204:GTP-Binding Proteins / Q000235:genetics*; D015870:Gene Expression; D020962:Heterotrimeric GTP-Binding Proteins; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D018895:Microsatellite Repeats; D008957:Models, Genetic; D008969:Molecular Sequence Data; D020161:Physical Chromosome Mapping; D013577:Syndrome; D014018:Tissue Distribution
chemical_list: D017931:DNA Primers; D019204:GTP-Binding Proteins; C119109:GNA14 protein, human; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins