The Search for GenesFinding the Gene is the First Step in Understanding the
Disease Process In almost every cell in our bodies, we have
approximately 100,000 genes that govern the way our body
develops and functions. We have two copies of each gene
because we inherit one copy from our mother and another
from our father. In humans, the genes are carried on 23
pairs of chromosomes. Each gene contains a specific DNA
(deoxyribonucleic acid) sequence that codes for a specific
protein. Linkage Analysis
The search for disease causing genes generally begins with
analysis of blood samples collected from multiple family
members and multiple families. From that blood, we obtain
the DNA. With enough samples from many families, we can
often determine the chromosomal location of the gene likely
to be responsible for the disease. This is called linkage
analysis. Candidate Genes
At the proposed location on the chromosome, there will
often be many genes whose functions are not known.
Therefore, next it is necessary to look at all the genes to
find the best possible "candidate" for the one that causes
the disease. DNA Sequencing
Once this candidate gene is found, the exact DNA sequence
is determined. The DNA samples from the affected
individuals in each family are then examined for
alterations in the DNA sequence. Some changes we find are
"benign" and cause no change in the protein product. These
are called polymorphisms. Other times the alteration causes
a big change in the protein product which is then
defective, or even absent. These changes are called
mutations. Mutations are changes in the normal DNA sequence
that lead to an abnormal protein product, and therefore an
abnormal function of that protein. Finding the gene is just the first step in understanding
a disease process. Once the gene is found and the protein
identified, it is then necessary to determine the protein's
normal function and its abnormal function. It is only
through these studies that we can then look at forms of
intervention and therapy. April 2002 | 
