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By Fred R.T. Nelson and Carolyn Taliaferro Blauvelt (Auth.)

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LFA-1 VLA-4 Leukocyte ICAM-1 VCAM-1 Endothelium Interstitial space Eosinophil Mononuclear cell Chemokine concentration gradient Inflammatory cell migration Chemokine release Epithelium Site of inflammation + IL-1, TFNα, IL-4 Fig. 29 Chemokines in leukocyte recruitment. g. eosinophil) adhere to endothelial adhesion molecules, diapedese between endothelial cells, and migrate along the chemokine gradient towards the site of inflammation. g. g. vascular cell adhesion molecule-1 (VCAM-1) or intercellular adhesion molecule-1 (ICAM-1)].

G. IL13 Genome scans Disease (Atopy/asthma) Map Scan whole genome for linkage or association to markers b Function Determine function of gene in relation to disease Gene Fine mapping of linked region – identify gene Fig. 2 Candidate gene versus genome-wide analysis. (a) In candidate gene analysis genetic variation in a gene selected on the basis of a known (or suspected) role in disease pathogenesis is tested for association with disease. (b) In genome-wide approaches (whether by linkage analysis in families or by genome-wide association studies), genetic variation across the genome is genotyped to identify a genetic region that underlies disease susceptibility.

For example, were they carried out in populations of similar genetic ancestry, or with similar environmental exposures? Were exactly the same polymorphisms studies in the gene and was the phenotype tested the same?  Source: Holloway JW, Yang IA, Holgate ST. Genetics of allergic disease. J Allergy Clin Immunol 2010; 125(2 suppl 2):S81–94. A positive association between the phenotype and the allele will occur if the allele is the cause of, or contributes to, the phenotype. This association would be expected to be replicated in other populations with the same phenotype, unless there are several different alleles at the same locus contributing to the same phenotype, in which case association would be difficult to detect, or if the trait was predominantly the result of different genes in the other population (genetic heterogeneity), or depended on interaction with an environmental exposure not present in the replication population.

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