Chronic Obstructive Pulmonary Disease Clinical Trial
To localize within the genome a chronic obstructive pulmonary disease susceptibility gene.
BACKGROUND:
Chronic obstructive pulmonary disease (COPD) is a slowly progressive disorder characterized
by airways obstruction that lasts for at least several months. The two major causes of COPD
are chronic bronchitis and emphysema. Either disorder may occur with or without airways
obstruction, but airways obstruction causes impairment of lung function leading to
disability and death. COPD is a major health problem in the United States and throughout the
world, consistently ranking among the most common causes of death in the United States.
Cigarette smoking is the primary environmental factor that increases the risk of COPD, but
other environmental factors have also been implicated. However, despite a well-established
role, environmental factors alone do not cause COPD. Symptomatic COPD develops in only 10-20
percent of heavy cigarette smokers, probably those with a genetic susceptibility, although
common COPD susceptibility genes have yet to be identified.
DESIGN NARRATIVE:
The study applied statistical linkage analysis to family data. Pulmonary measurements had
already been collected on 159 members of 16 pedigrees and evidence supporting a COPD
susceptibility gene in these pedigrees had been obtained from segregation analysis. Each of
11,995 genetic markers, which had already been genotyped on pedigree members, were tested
for evidence of linkage to the inferred COPD susceptibility gene. Evidence of linkage to one
or more genetic markers identifed genomic locations of COPD susceptibility genes. The high
density of markers allowed fine-mapping of the gene. Successful completion of this gene
localization project was the necessary prerequisite for a project to identify and
characterize a COPD susceptibility gene. Identifying a gene that when mutated increased the
risk of COPD may increase understanding of pulmonary function, as well as allowing
gene-carriers to be identified and made aware of their susceptibility.
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