Edited by Jeanette M. Smith, MD, Catherine D. DeAngelis, MD, MPH, and
Roger N. Rosenberg, MD
Four research articles in this issue of THE JOURNAL report the identification
of genetic risk factors for 3 common diseases. A complete genomic screen for
linkage analysis in 174 families with at least 2 family members with idiopathic
Parkinson disease (PD), conducted by Scott and colleaguesArticle, suggests that the
parkin gene is influential in the development of early-onset PD and that several
genes may be important in the development of late-onset PD. Martin and colleaguesArticle,
using genetic linkage and positional association analyses, found an association
between the tau gene and idiopathic PD. Athan and colleaguesArticle identified a
Gly206Ala mutation in presenilin 1 in 8 of 19 unrelated Caribbean Hispanic
families with early-onset familial Alzheimer disease. In mutation analyses
of the cardiac sodium channel gene, SCN5A, in postmortem
cardiac tissue from cases of sudden infant death syndrome or undetermined
infant death, Ackerman and colleaguesArticle found that 2 of 93 cases had SCN5A channel mutations that increased late sodium current—a
defect associated with risk for fatal arrhythmias.
Identification of genetic determinants of an individual's response to
drug therapy affords the possibility of selecting specific therapy likely
to benefit an individual and of reducing adverse drug outcomes. Previously
published results of the Breast Cancer Prevention Trial showed that among
high-risk, cancer-free women who received prophylactic tamoxifen, the incidence
of invasive breast cancer was reduced compared with the placebo group. In
this analysis of data from participants in this trial, King and colleaguesArticle
found that the incidence of breast cancer was reduced (nonsignificantly) among
women with BRCA2 mutations who received tamoxifen
compared with placebo, but not among women with BRCA1
mutations. In a systematic review of studies on adverse drug reactions (ADRs)
and review articles on variant alleles of genes for drug-metabolizing enzymes,
Phillips and colleaguesArticle found that 16 of 27 drugs commonly cited in ADR studies
are metabolized by at least 1 enzyme with a variant allele known to cause
Pekarsky and colleagues review the molecular pathogenesis of T-cell
chronic lymphocytic/prolymphocytic leukemia, beginning with the activation
of the TCL1 locus at chromosome 14q32.1, and discuss
the potential for targeted drug development based on the specific oncogenic
pathways of this disease.
The risks and benefits for human participants in population-based genetic
research studies differ from those typically associated with clinical research.
Beskow and colleaguesArticle discuss an informed consent document and supplemental
brochure that they developed to enable individuals to make informed decisions
about participation in population-based genetics research. In a commentary,
AnnasArticle observes that the current system of protecting human subjects focuses
excessively on the consent document, and emphasizes the importance of the
informed consent process as one of education and explanation for prospective
Clinical applications of proteomics.
Issues that complicate the use of DNA microarrays for gene expression
Perspectives on advances in genetics: McKusickArticle on the history of medical
genetics, Subramanian and coauthorsArticle on the implications of new genomic knowledge
for biomedical research and medical practice, and Collins and GuttmacherArticle on
ways that genetics is moving into mainstream medicine.
For your patients: A genetics primer.
Web-enhanced articles with links from genetics terms to their definitions
in the National Human Genome Research Institute Glossary of Genetics Terms.
This Week in JAMA. JAMA. 2001;286(18):2203. doi:10.1001/jama.286.18.2203