Genomic Organization of the Human Gα14 and Gαq 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 Gα14, a member of the G-protein α-subunit multigene family, and have identified Gαq in the contig. The genomic structure of both genes has been established after construction of a bacterial artificial chromosome contig that showed Gαq and Gα14 to be in a head-to-tail arrangement (Cen–Gαq–Gα14–qter). Northern analysis found Gαq to be ubiquitously expressed and Gα14 to display a more restricted pattern of expression. Mutation analysis of the coding regions and splice sites for Gαq and Gα14 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 Gα14 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.