title: Molecular genetic analysis of recessive mutations at a heterozygous autosomal locus in human cells.
abstract: We have investigated the genotypic changes that lead to expression of a recessive allele at a heterozygous autosomal locus in a human cell line. Mutant clones lacking thymidine kinase activity were derived from a B-cell lymphoblastoid line initially heterozygous at the tk locus, and restriction mapping was performed to detect intragenic structural alterations in the tk gene. In addition, informative molecular markers located elsewhere on chromosome 17 were analysed in order to detect large-scale (multilocus) events. We report that among 325 spontaneous and induced mutants, allele loss was more common than intragenic rearrangements or point mutations; in many cases, loss of heterozygosity appears to have extended well beyond the locus under selection. Cytogenetic analysis of a subset of these mutants showed that expression of the recessive TK-deficient phenotype and the associated loss of heterozygosity for chromosome 17 markers was not typically associated with detectable chromosomal changes.
authors.affiliation: Department of Cancer Biology, Harvard School of Public Health, Boston, MA 02115.
authors.forename: D W
authors.initials: DW
authors.lastname: Yandell
authors.forename: T P
authors.initials: TP
authors.lastname: Dryja
authors.forename: J B
authors.initials: JB
authors.lastname: Little
mesh_terms: D015139:Blotting, Southern; D002460:Cell Line; D002871:Chromosome Banding; D002886:Chromosomes, Human, Pair 17; D002999:Clone Cells; D004247:DNA / Q000235:genetics; D015870:Gene Expression; D005808:Genes, Recessive; D005819:Genetic Markers; D006579:Heterozygote; D006801:Humans; D007621:Karyotyping; D009153:Mutagens; D009154:Mutation; D012150:Polymorphism, Restriction Fragment Length; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics*; D014466:Ultraviolet Rays; D014965:X-Rays
chemical_list: D005819:Genetic Markers; D009153:Mutagens; D004247:DNA; D013937:Thymidine Kinase