ISIS, the intron information system, reveals the high frequency of alternative splicing in the human genome.
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Biomedical subjects
Publications and source records attributed to L Croft.
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From clinically based series it has been proposed that, in homozygotes for the apolipoprotein E epsilon 4 (apoE epsilon 4) allele, Alzheimer's disease is almost inevitable by the age of 80. A population sample of persons aged 70 years and over was interviewed in 1990-91 to ascertain the presence of dementia or cognitive impairment. The sample was reinterviewed in 1994, when the apoE genotype was also determined. Prevalence data for the 638 persons who completed the second examination revealed a linear association between having an apoE epsilon 4 allele and both dementia and cognitive impairment (for heterozygotes, odds ratio for dementia 1.89, 95% confidence interval 1.04-3.44 and for homozygotes OR 3.58, 95% CI 1.08-11.82; both adjusted for age). However, even in subjects homozygous for epsilon 4 the estimated prevalence of dementia by age 90 was only about 50%. Persons with one or two epsilon 4 alleles were more likely to have a family history of dementia than those with none. This study confirms in a population sample that the epsilon 4 allele is a risk factor for dementia, but refutes the suggestion that homozygosity for the epsilon 4 allele is sufficient for the development of Alzheimer's disease: persons with either one or two epsilon 4 alleles may reach late old age without cognitive impairment.
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The monoclonal antibody W6/32.1 recognizes a public determinant on the HLA-A, B and C antigens of all tested human haplotypes. Though the antibody does not bind to normal mouse cells of any H-2 haplotype, it does show an unexpected specificity for the T cell leukemia line MBL-2 from a C57BL/6 mouse. It is shown that the murine antigen recognized by W6/32.1 is on an H-2-like molecule which also carries the determinant recognized by the monoclonal antibody B22-249 R1, specific for the H-2Db antigen. Unlike B22-249 R1, however, W6/32.1 does not bind to normal H-2b lymphocytes, nor to a variety of tumor cell lines of the H-2b haplotype. This cross-reaction is specific to W6/32.1, and is not shared by other monoclonal antibodies of similar anti-HLA specificities. Moreover, the affinity of W6/32.1 for its human antigen is substantially higher than for its mouse antigen. We conclude that W6/32.1 fortuitously recognizes a novel determinant on the H-2Db antigen of MBL-2, rather than an extensive region of structural homology shared between HLA and H-2. Thus for cells of the H-2b allotype this determinant is detected only on MBL-2, and by definition is thus an example of a tumor-associated antigen.
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