In an Australian population phenotyped for atopy and BHR, 172 affected sib-pairs were identified and screened with 269 markers spanning the entire genome. There was linkage of total serum IgE to the FceRI-P locus (chromosome llq) and to another locus on chromosome 16. BHR was linked to a locus on chromosome 4 and another on […]

5-Lipoxygenase(5-LO) Gene Polymorphism and Asthma 5-LO is an enzyme that mediates the derivation of leukotrienes from arachidonic acid. Leokotrienes are mediators of airway inflammation and bronchocon-striction. Treatment with zileuton, a 5-LO inhibitor, has been shown to improve asthma control.91 A polymorphism has been identified in the promoter region of the 5-LO gene that decreases gene […]

fi2-Adrenergic Receptor (ft2AR) Polymorphisms and Asthma The (32AR is expressed on a number of cell types in the lung, including mast cells and bronchial smooth muscle cells. It is the target for b2AR agonists, one of the most effective class of bronchodilating drugs. Altered (32AR expression or function has been shown to accompany asthma by […]

HLA, TCR Genes, and Antigen-Specific IgE Responses Why is it that some people develop allergy to an antigen while others do not? In other words, what are the determinants of antigen-specific IgE responses? Clearly, timing, mode, and intensity of antigen exposure are important environmental determinants. Now there is evidence that human leukocyte antigen (HLA) and […]

Linkage of Atopy and BHR to Chromosome 5q Cytokines play a major role in the development of atopy and asthma. The genes for many of these cytokines, including interleukin-3,4,5,9,13, and gran-ulocyte-macrophage colony-stimulating factor, have been mapped to a small region on 5q31-33 known as the “cytokine-gene cluster.”66 Under the hypothesis that one of these cy […]

Linkage of Atopy to Chromosome 11 The first evidence for linkage of atopy with a specific chromosomal region was provided by Cookson et al46 in British families. They typed only 17 markers in seven families with atopy and found strong evidence of linkage of atopy to marker D11S97 on chromosome 11 ql3. They confirmed this […]

Two types of linkage analysis, parametric and nonparametric, are available. 1. Parametric Linkage Analysis: This is the classic approach and often the unqualified term “linkage analysis” is used to describe this approach. Extended pedigrees are the best substrate for this approach. A model of inheritance is proposed (hence the term “parametric”). First, the likelihood of […]