Genomic organization of the human G alpha 14 and G alpha q genes and mutation analysis in chorea-acanthocytosis (CHAC)

Chorea-acanthocytosis (CHAC) (OMIM 200150) is a rare neurological syndrome characterized by neurodegeneration in combination with morphologically abno rmal red cells (acanthocytosis). A partial yeast artificial chromosome cont ig of the CHAC critical region on chromosome 9q21 has been constructed, and 21 expressed sequence tags have been mapped. We have subsequently cloned G alpha 14, a member of the G-protein alpha-subunit multigene family, and ha ve identified G alpha q in the contig. The genomic structure of both genes has been established after construction of a bacterial artificial chromosom e contig that showed G alpha q and G alpha 14 to be in a head-to-tail arran gement (Cen-G alpha q-G alpha 14-qter). Northern analysis found G alpha q t o be ubiquitously expressed and G alpha 14 to display a more restricted pat tern of expression, Mutation analysis of the coding regions and splice site s for G alpha q and G alpha 14 in 10 affected individuals from different fa milies identified no changes likely to cause disease; however, two distinct single nucleotide polymorphisms in the coding region of G alpha 14 have be en identified, This study has excluded two plausible candidate genes from i nvolvement in CHAC and has provided a solid platform for a positional cloni ng initiative. (C) 1999 Academic Press.