A rapid method has been developed and used to search for restriction fragment length polymorphisms (RFLPs) that are in linkage disequilibrium with diseaseassociated loci. By using genomic blot-hybridization analysis with DQ (-chain and DR fl-chain cDNA probes, we examined DNA polymorphisms within the HLA class II loci associated with susceptibility to insulin-dependent mellitus (IDDM). To facilitate the search for informative RFLPs, we compared pooled DNA samples from IDDM patients with pooled DNA samples from randomly selected control individuals, instead of using the conventional approach of examining DNA samples from individuals in two groups. (The conditions under which this approach is useful are treated theoretically in the Appendix.) Several specific polymorphic restriction fragments associated with IDDM were revealed by using this economical and rapid approach. The restriction enzymes and probes identified as informative in this screening were then used to analyze HLA-DR-typed IDDM families, homozygous typing cells, and unrelated individuals to determine the association of the specific restriction fragments with HLA-DR serological type and the frequency in control and IDDM populations. Some individual polymorphic fragments for which the IDDM population was enriched correlated strongly with HLA-DR3, whereas others correlated strongly with HLA-DR4. Some fragments (e.g., a 10-kilobase Taq I fragment detected with the DRY3 probe) that were more prevalent in the IDDM population subdivided the serologically defined HLA-DR type and may be informative markers for IDDM susceptibility.DNA polymorphisms tightly linked to loci at which mutations cause disease or disease susceptibility can serve as useful genetic markers to elucidate modes of inheritance and as a tool for genetic diagnosis. If a particular polymorphic variant is in linkage disequilibrium with the disease-related locus, then the DNA polymorphism can be informative beyond its value as a marker in linkage analysis, as was the association between sickle-cell anemia and a 13-kilobase (kb) Hpa I restriction fragment of the /8-globin gene (1).Genetic susceptibility to a number of diseases shows linkage as well as association in population studies with specific serologically defined variants of the HLA class I and class II loci (reviewed in ref.2). These loci encode cell surface glycoproteins that mediate a variety of immune functions. The association of many diseases that have an autoimmune component, such as insulin-dependent diabetes mellitus (IDDM), with serologically defined class II variants (HLA-DR types) suggests the existence of disease-susceptibility-related genes in linkage disequilibrium with specific serologic markers. It is not known whether the class II gene products are themselves involved in disease causation and, if so, whether the variants of the polymorphic sequences that form the basis of immunologic typing are the same ones that confer disease susceptibility.The genetic basis of IDDM susceptibility is complex; 60-80% of the gene...
The Australian system of mandatory detention of asylum-seekers has become increasingly controversial. Insofar as commentary on detention has been framed historically, critics have pointed to Australia's race-based exclusionary laws and policies over the twentieth century. In this article, we suggest that exclusion and detention are not equivalent practices, even if they are often related. Here we present an alternative genealogy of mandatory detention and protests against it. Quarantine-detention and the internment of "enemy aliens" in wartime are historic precedents for the current detention of asylum-seekers. Importantly, in both carceral practices, non-criminal and often non-citizen populations were held in custody en masse and without trial. Quarantine, internment and incarceration of asylum-seekers are substantively connected over the twentieth century, as questions of territory, security and citizenship have been played out in Australia's histories of detention.
No abstract
In the wake of Foucault's provocative philosophical contributions to the study of discipline and punishment, social and legal historians no longer narrate penal history as a straightforward tale of moral and political progress. In its place is a schematic picture of a large-scale retreat from the body to the prison as the prime site of punishment. Historiographical proclivities perpetuate that image: early modernists tend to concentrate on the Bloody Code and similar régimes of terror, whereas historians of the twentieth century specialize in studies of regulatory modes of punishment and “normalization.” These latter works include histories of reformatories, family courts, social workers, psychiatric experts—in short the institutions and agents that best instantiate the reorientation toward disciplining the soul and governing the self. Scholars who study corporal and capital punishment in the twentieth century would seem to have nothing to add, other than to remark that there were exceptions in the wider history of penal change.
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