GM1-gangliosidosis: Chromosome 3 assignment of the?-galactosidase-A gene (? GAL A )

Abstract

The structural gene (βGAL_A) coding for lysosomal β-galactosidase- A (EC 3.2.1.23) has been assigned to human chromosome 3 using man-mouse somatic cell hybrids. Human β-galactosidase-A was identified in cell hybrids with a species-specific antiserum to human liver β-galactosidase-A. The antiserum precipitates β-galactosidase-A from human tissues, cultured cells, and cell hybrids, and recognizes cross-reacting material from a patient with G_M1 gangliosidosis. We have analyzed 90 primary man-mouse hybrids derived from 12 separate fusion experiments utilizing cells from 9 individuals. Enzyme segregation analysis excluded all chromosomes for βGAL_A assignment except chromosome 3. Concordant segregation of chromosomes and enzymes in 16 cell hybrids demonstrated assignment of βGAL_A to chromosome 3; all other chromosomes were excluded. The evidence suggests that G_M1 gangliosidosis is a consequence of mutation at this βGAL_A locus on chromosome 3.