Principal steps in gene identification

To identify a suspected human disease gene,
clinical and family data together with blood
samples for DNA must be collected from
patients with the same particular disorder. The
disorder may follow one of the three modes of
monogenic inheritance (autosomal recessive,
autosomal dominant, X-chromosomal; 1) or
multigenic complex inheritance (not shown).
Genetic heterogeneity must be ruled out. A
chromosome region likely to harbor the gene is
then identified by one of the genetic mapping
techniques (linkage analysis or physical mapping
using a chromosomal structural aberration
such as a deletion or a translocation) (2). The
map position is refined and the gene location is
narrowed to a small area, e.g., a visible chromosome
band within 2–3 Mb (3). A contig of overlapping
DNA clones froma YAC or BAC (bacterial
artificial chromosome) or a cosmid library is established
from the region (4). This results in a
refined molecular map (5) characterized by a
set of localized polymorphic DNA marker loci