Genetic Factors

Multiple twin and family analyses strongly imply a genetic basis for asthma and atopy [5, 17]. A recent study of 11,688 Danish twin pairs suggested that 73% of asthma susceptibility is due to genetic factors [18]. However, atopy-associated phenotypes do not appear to follow any Mendelian inheritance pattern, which is characteristic of complex genetic (multifactorial) traits. The dissection of these traits is hampered by phenocopy, incomplete penetrance, and genetic heterogeneity. The complexity of the genetics of asthma and atopy is reflected by an increasingly large number of chromosomal regions showing (mostly weak to moderate) evidence for linkage, as well as various genetic variations in multiple candidate genes that are associated with asthma or associated phenotypes.

Multiple chromosomal regions showed evidence for linkage to asthma and atopy. Few regions show evidence for linkage in more than one population, which may be due to racial differences, a different definition of phenotypes or (most likely) insufficient numbers of affected sib pairs. Theoretically, at least 1,000 affected sib pairs seem to be required to avoid type 1 and type 2 errors in genetic analyses of complex traits.

A genome-wide linkage study in nuclear families of European origin with affected siblings with early age of onset atopic dermatitis revealed highly significant evidence for linkage on chromosome 3q21 (Zall = 4.31, p = 8.42 X 10~6). Moreover, this locus provided significant evidence for linkage of allergic sensiti-zation under the assumption of paternal imprinting (hlod = 3.71; a = 44%), further supporting the presence of an atopy gene in this region [20].

Despite the high degree of inconsistent findings, it is intriguing that chromosomal regions linked to asthma have also shown evidence for linkage to other inflammatory and autoimmune diseases. Regions linked to atopic dermatitis have also been linked to psoriasis [21].

Candidate Gene Studies

This approach is chosen to test whether chromosomal regions containing distinct genes (of known biological function and location) are linked to disease, followed by mutational analysis of respective candidate genes. Commonly, genotyping of selected STRPs that map closely to candidate genes (e.g. IL-4) is performed in affected sib pairs (allele-sharing analysis) or trios [affected offspring and parents; transmission disequilibrium test (TDT) analysis] to establish linkage.

The most solid chromosomal regions showing evidence for linkage or associations with atopy-related traits are on chromosome 6p, 5q, 11q, 12q and 13q. These chromosomal regions contain many genes that are critically involved in the allergic inflammation. Screening for mutations/polymorphisms in the majority of the candidate genes has been performed. Multiple (mostly weak to moderate) associations with atopy-related traits have been reported [22-24].

Coping with Asthma

Coping with Asthma

If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.

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