ABSTRACT
The gene for spinocerebellar ataxia 7 (SCA7) includes a transcribed, translated CAG tract that is expanded in SCA7 patients. We have determined expansions in 73 individuals from 17 SCA7 kindreds and compared them with repeat lengths of 180 unaffected individuals. Subjects with abnormal expansions comprise 59 clinically affected individuals and 14 at-risk currently unaffected individuals predicted to carry the mutation by haplotype analysis. For expanded alleles, CAG repeat length correlates with disease progression and severity and correlates inversely with age of onset. Increased repeat lengths are seen in generational transmission of the disease allele, consistent with the pattern of clinical anticipation seen in these kindreds. Repeat lengths in expanded alleles show somatic mosaicism in leukocyte DNA, suggesting that these alleles are unstable within individuals as well as between generations. Although dynamic repeat expansions from paternal transmissions are greater than those from maternal transmissions, maternal transmission of disease is more common, suggesting germline or embryonic effects of the repeat expansion.
Subject(s)
Genomic Imprinting , Nerve Tissue Proteins/genetics , Spinocerebellar Degenerations/genetics , Trinucleotide Repeats , Adolescent , Adult , Age of Onset , Alleles , Analysis of Variance , Ataxin-7 , Base Sequence , Child , Child, Preschool , DNA Primers , Disease Progression , Female , Humans , Male , Middle Aged , Nerve Tissue Proteins/biosynthesis , Pedigree , Polymerase Chain Reaction , Protein Biosynthesis , Reference Values , Regression Analysis , Spinocerebellar Degenerations/physiopathology , Transcription, GeneticABSTRACT
Concepts and methods of continuous quality improvement have been endorsed by quality specialists in American Health care, and their use has convinced CEOs that industrial methods can make a contribution to health and medical care. For all the quality improvement publications, there are still few that offer a clear, concise definition and an explanation of the primary tools for teaching purposes. This report reviews ten continuous quality improvement methods including: problem solving cycle, affinity diagrams, cause and effect diagrams, Pareto diagrams, histograms, bar charts, control charts, scatter diagrams, checklists, and a process decision program chart. These do not represent an exhaustive list, but a set of commonly used tools. They are applied to a case study of bed utilization in a university hospital.
