title: Sandhoff disease heterozygote detection: a component of population screening for Tay-Sachs disease carriers. I. Statistical methods.
abstract: Serum and leukocyte hexosaminidase profiles (total activity and percent heat-labile activity levels) in obligate Sandhoff disease (SHD) heterozygotes differ from those of obligate Tay-Sachs disease (TSD) heterozygotes and noncarrier individuals. We have developed a procedure to identify, with 95% sensitivity, carriers of the allele(s) for SHD among individuals screened in a TSD heterozygote identification program. Using multivariate statistical methods of cluster analysis and discriminant analysis on serum and leukocyte hexosaminidase profiles from 102 potential SHD carriers, a linear discriminant function to classify individuals as SHD carriers or SHD noncarriers was constructed. This function classifies the serum and leukocyte profiles from all 15 obligate SHD heterozygotes studied, as those of SHD carriers. A 95% isodensity ellipse derived from only the serum hexosaminidase profiles of the 15 SHD obligate carriers has been applied to a TSD screened sample of 37,843 Jewish and non-Jewish individuals. A potential recall rate of screened individuals for serum retests and leukocyte assays of 2.01% has been estimated. These statistical methods enhance the TSD heterozygote screening program by permitting one to detect SHD heterozygotes within the screened population.
mesh_terms: D006580:Genetic Carrier Screening; D005820:Genetic Testing; D006596:Hexosaminidases / Q000172:deficiency / Q000235:genetics; D006801:Humans; D007585:Jews; D007962:Leukocytes / Q000201:enzymology; D012497:Sandhoff Disease / Q000201:enzymology / Q000235:genetics*; D013223:Statistics as Topic; D013661:Tay-Sachs Disease / Q000201:enzymology / Q000235:genetics*
chemical_list: D006596:Hexosaminidases