A young Spokane business, Signature Genomic Laboratories LLC, has positioned itself on the leading edge of commercial genetic technology by employing a relatively new molecular technique to diagnose chromosome abnormalities in human patients.


In the U.S., only the Baylor College of Medicine, in Houston, where Signature partners Lisa Shaffer, a geneticist, and Dr. Bassem Bejjani previously were cytogenetics laboratory director and medical director, respectively, is also equipped to make such diagnoses commercially, asserts Bejjani.


Signature Genomic employs 12 people in 1,200 square feet of space it leases from Sacred Heart Medical Center in the Health Resource Center at 44 W. Sixth. A promise by Sacred Heart to invest in the company lured the two research scientists to Spokane in 2002, says Shaffer. They formed a limited liability company with Sacred Heart in May 2003 and launched a commercial enterprise last March.


Last May, the young company did four chromosome analyses. Now it is doing 40 a week, says Bejjani.


We are already a national player in chromosome analysis and are starting to get business from all over the world, he says.


Signature uses a technology, called microarray, to study a patients DNA quickly, making comparisons between a carefully selected cloned DNA, and both patients DNA and normal, or control, DNA.


Each human being should have the same basic DNA, with the exception of the sex chromosome, says Bejjani. When human beings dont have the same basic DNA, problems can occur.


DNA, or deoxyribonucleic acid, is the basic material in chromosomes and contains a persons genetic code. Through its use of the science of microarray, Signature Genomic produces a computer-generated double line graph that depicts the selected normal DNA and the patients DNA, making abnormalities readily apparent.


The testing is so specific that analysis can be run on any of the trait-telling 23 chromosomes in a humans body. For example, a second chromosome No. 21 is present in persons with Down Syndrome.


Although the basic DNA should be the same for all humans, the specific information that DNA provides in differentiating one person from another goes much deeper. Like a book, the sum total of pages across the whole genomethe sum total of all of the genes of a personshould be the same, while someone with mental retardation, for instance, would have several pages missing, Bejjani says.


Signature Genomics focus, in effect, is on how many and which pages exist in a patients genome. The information on the pages themselves that identifies unique characteristics about individuals is studied by others through a different technology called DNA sequencing.


The advantage of microarray is that it allows a satellite view of the genome at an unprecedented resolution, says Bejjani.


Although the need for chromosome testing may appear obvious for children with birth defects, many parents, through doctor referrals, seek answers when they realize their kids differ from other children, says Shaffer. Though most chromosome-studied individuals are children, adults are tested as well.


The practicality of each analysis, for which Signature Genomic charges $1,650, is to give a scientific explanation for an abnormality, to give parents the exact odds of a recurrence in future offspring, and to share DNA-specific information about anticipated future medical complications such as cancer and kidney failure.


A future use of microarray technology could be for pre-natal tests, especially for women over the age of 35, who because they are in advanced childbearing years, sometimes will have children with problems, says Bejjani.


He is realistic about the fact that for now, a subjects DNA cant be altered to correct a problem.


We cant put DNA back in them, he says. He makes an analogy between the complexity of repairing DNA abnormalities and the baking of a cake, and says, If you discover the cake is made wrong, you cant undo the cake.


Cytogenetics, the study of human chromosomes, was begun in the early to mid-1970s, says Shaffer. It is primarily a microscope-based discipline in which technicians perform a very tedious and detailed visual analysis of the chromosome, says Bejjani.


In the late 1980s a breakthrough called Fluorescence In Situ Hybridization, or FISH for short, enabled scientists to study simultaneously one to five specific sites on the chromosomes with DNA probes.


Laboratory scientists next made breakthroughs in the microarray technique in 1997. Signature Genomic was the first company to adopt, modify, and optimize that technology in a clinical setting, says Bejjani.


Signature Genomic spent several months selecting the exact cloned pieces of DNA it would uses on its arrays. Thousands and thousands of cloned DNAs are available from institutions and companies, but mistakes can be made, and the company needed to be absolutely certain it was using the right DNA, Bejjani says. Also, the genome is complicated and has repetitive sequences that Signature Genome wanted to avoid.


The Spokane company has invested in two computer-controlled robots, at a combined cost of about $250,000, that place the miniscule cloned DNA on microscope slides. The newer and larger of the two machines loads 300 slides in a four-hour period, and the second robot loads 50 slides in the same time.


When the robots put the cloned DNA on a microscope slide, they shred the entire human genomethe sum total of all of the genes in an individualinto small pieces that they array on the slide. The cloned DNA provides a basis for comparing the patients DNA and the normal DNA. The DNA from the patient and the normal DNA also are of the entire genome. DNA from any normal male or female can be used as the normal DNA, says Shaffer.


Shaffer says microarray technology now can provide information on 831 DNA segments on one slide, although that number is growing as the science improves.


Once a robot creates an array by placing the cloned DNA in tiny rows and columns on a microscope slide, the slide is taken from the robot and manually labeled, numbered, and catalogued according to diagnostic laboratory standards.


DNA from the patient and the normal DNA are treated separately with two different colors of fluorescent dye, are mixed together, and then are allowed, through a process called hybridization, to find their perfect DNA match on the microarray of cloned DNA. DNA seeks to attach itself to DNA that looks like itself, Bejjani says. The patient DNA and the normal DNA attach themselves proportionately onto the spots of the arrayed DNA for which they have equal amounts, but one will attach itself in higher amounts to areas of the genome where the patient and the control dont have equal amounts of DNA. That difference will be visualized as a difference in the color of the dye. Because the microarray has been printed in a certain way, the software knows exactly what spot on the slide represents what area of the genome.


The slide is then inserted into a dual-laser scanner thats capable of differentiating between DNA data accentuated by the two different colors of dye. That specialized microscope computer scans the slide and extracts chromosome-specific information from the dye-coated samples and plots the information on a line graph. The DNA in the normal specimen usually projects in a straight, horizontal line, while any abnormalities in the patient DNA deviate from that norm.


Based on their training, Shaffer and Bejjani can identify the variations in the patients DNA and diagnose the problem.


Chromosome analysis is not new, but the speed and accuracy of microarray diagnostics is, says Bejjani. Shaffer estimates that there are 500,000 chromosome analyses done annually in the U.S., almost all of them with slower, microscope-based technology. She thinks Signature Genomic will get a growing share of the market for quicker analyses. It has the ability to complete a chromosome analysis in five days, and she asserts that the growth potential for the company is exponential.


Signature Genomics is now growing at a rate at which it adds about three new employees every three or four months and before long will be looking to own its own building, says Shaffer. That building might consist of a 10,000-square-foot laboratory with another 5,000 square feet for office space, she says.


We definitely want to stay in Spokane, says Shaffer. She says there are four major universities and colleges in the area that produce bio-technology graduates who can fill the companys labor needs.


Its a great place for us, and the airport is close, says Bejjani.