ABSTRACT
BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease associated with contraction of arrays of tandem 3.3-kb units (D4Z4) on subtelomeric 4q. Disease-linked arrays usually have fewer than 11 repeat units. Equally short D4Z4 arrays at subtelomeric 10q are not linked to FSHD. The newly described 4qA161 haplotype, which is more prevalent in pathogenic 4q alleles, involves sequences in and near D4Z4. METHODS: We developed two new assays for 4qA161, which are based upon direct sequencing of PCR products or detecting restriction fragment length polymorphisms. They were used to analyse single nucleotide polymorphisms (SNPs) indicative of 4q161 alleles. RESULTS: All (35/35) FSHD patients had one or two 4qA161 alleles (60% or 40%, respectively). In contrast, 46% (21/46) of control individuals had no 4qA161 allele (p<10(-4)), and 26% had homozygous 4qB163 alleles. CONCLUSIONS: Our results from a heterogeneous population are consistent with the previously described association of the 4qA161 haplotype with FSHD, but a causal association with pathogenesis is uncertain. In addition, we found that haplotype analysis is complicated by the presence of minor 10q alleles. Nonetheless, our sequencing assay for the 4qA161allele can enhance molecular diagnosis of FSHD, including prenatal diagnosis, and is simpler to perform than the previously described assay.
Subject(s)
Chromosomes, Human, Pair 4/genetics , Haplotypes/genetics , Muscular Dystrophy, Facioscapulohumeral/genetics , Telomere/genetics , Base Sequence , Humans , Molecular Sequence Data , Muscular Dystrophy, Facioscapulohumeral/diagnosis , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Polymorphism, Single Nucleotide , Reproducibility of Results , Sensitivity and Specificity , Sequence Analysis, DNA/methods , Sequence Homology, Nucleic Acid , Tandem Repeat Sequences/geneticsABSTRACT
Groups, like individuals, often develop habitual routines for dealing with frequently encountered stimuli. Although such routines are consequential for group life and work, little is known about them. This paper reconnoiters the territory of habitual behavior in groups that perform work within organizations. We offer a definition of group habits, identify their functions and dysfunctions, suggest how they develop and are maintained, and identify the circumstances when they are likely to be altered or abandoned. Throughout, we give special attention to the social nature of habitual routines in groups, to the interaction between habitual behavior and group life cycle phenomena, and to the role of the organizational context in prompting, shaping, and terminating habitual routines.
