I believe that there are three major developments what will greatly alter the way all disciplines of medicine, including dermatology, will be practiced during this century. These developments are the employment of genomics for the diagnosis of various inheritable diseases and disease traits, stem cells use in therapy and gene therapy. For this message, I will focus the increasing role of genomics in medical diagnosis.

The Human Genome Project (HGP) began in 1991 and was, for the most part, completed in 2003. This was an international scientific research project to determine the sequence of base pairs of DNA and to identify the approximately 20,000 – 25,000 genes of the human genome from both a physical and functional standpoint. The HGP has succeeded in mapping the nucleotides contained in a haploid human genome containing more than three billion base pairs.  The genome of any given individual is unique.  Therefore, mapping “the human genome” involves sequencing multiple variations of each gene.

DNA in the human genome is arranged into 24 distinct chromosomes, 22 autosomal chromosomes and an x and a y chromosome.  Each chromosome is composed of various lengths containing 50 million to 250 million base pairs. A few types of chromosomal abnormalities, including missing or extra copies or gross breaks and rejoining (translations), can be detected by microscopic examination. Most changes in DNA, however, are more subtle and require analysis of the DNA molecule to find perhaps a single base difference.

Each chromosome contains many genes. However, genes comprise only about 2% of the human genome; the remainder consists of non-coding regions, whose function may include chromosomal structural integrity and regulating where, when, and in what quantities gene induced proteins are made.

Slight variation in DNA sequences can have a major impact on whether or not a human will develop a disease and or a particular response to environmental insults such as bacteria, viruses, and toxins. These variations may also impact our response or reaction to drugs and other therapies.  One of the most common types of sequence variation is the single nucleotide polymorphism (SNP). SNPs are the sites in the human genome where individuals differ in their DNA sequence, often by a single base.  SNP maps are used to identify multiple genes associated with such complex diseases such as cancer, diabetes, and heart disease.                                                                                              
Genetic disease may be the result of defects in one gene (monogenic or Mendelian) patterns (autosomomal dominant, recessive, x-linked). Other genetic linked diseases are polygenic, involving defects of more than one gene. These diseases are manifest as a result of interaction of genetic and environmental factors.

Specific gene loci and their proteins have been identified for many of the monogenic diseases, including most of the genodermatoses. Specific targeted therapies should be developed and directed towards these diseases in the near future.

We are becoming more aware of the genetic influence on many common chronic diseases such as type II diabetes mellitus, migraines, schizophrenia, and heart disease. More and more genomic sequence variants in particular genes associated with these diseases are being discovered, but overall cause is complex involving the interaction of the genetic and environmental factors.  There are now companies that can assess an individual’s genetic risk factors by analyzing SNP markers from their DNA. One such company is Navigenics which uses the DNA in patient’s saliva to analyze their genome to relay their propensity for genetic risk factors for such diseases as type II diabetes, heart attack, Alzheimer’s disease, lupus erythematosus, psoriasis, and various cancers. Assessment for genetic risk factors for atopic dermatitis and various specific skin cancers should become available. When these genetic markers are combined with environmental triggering factors, a risk probability of disease occurrence can be calculated.  Physicians can then be alerted to plan for measures of intervention.

I believe the day will soon come where the genotype of newborn infants will be available as commonly as the information on blood type. With this information, physicians will be able to proactive in disease prevention from a logical preventative medicine standpoint.