Fallout from the Human Genome Project
Have you noticed that the Human Genome Project (and related genetic research) is affecting your daily practice? I’m sure you have, as already last year Dr. Keren devoted his Editorial and a good part of The Warde Report to BRCA1 and BRCA2 gene testing in breast cancer families.
In 1990, we established the DNA Diagnostic Laboratory for the testing of heritable disease mutations. In that year, testing was available for sickle cell, cystic fibrosis, and the DNA triplet-repeat expansion associated with the Fragile X syndrome (see article). The fragile X test was previously a relatively unreliable and considerably more expensive chromosome test for the expression of the X-linked fragile site. Today, in collaboration with Warde, our laboratory offers over 20 different assays including heritable disorders expressed in childhood such as Prader-Willi and Angelman syndromes and myotonic dystrophy, heritable predisposition to endocrine cancers (familial medullary thyroid cancer and the MEN2 syndromes), numerous disorders of importance for hematology (prothrombin, Factor V Leiden, MTHFR, hemochromatosis, sickle cell, and hemoglobin C), and most recently hereditary pancreatitis. The cystic fibrosis PolyT allele and the fragile X syndrome locus are of special interest to infertility workers because of their association with congenital absence of the vas deferens and with premature ovarian failure, respectively. If those aren’t enough to remember, we expect to offer another 20 or so additional genetic assays within the next two years. Fallout from the Human Genome Project!
We cytogeneticists, not a group to be upstaged, and never forgetting the usurpation of Prader-Willi and Fragile X by the molecular geneticists, have brought you FISH (fluorescent in situ hybridization). FISH allows us to, for example, identify the number of individual chromosomes in interphase cells, and to visualize leukemia-associated chromosome rearrangements and nearly sub-microscopic deletions and duplications. The FISH techniques and some of the important microdeletion syndromes are briefly described in this issue of the Warde Report (see article).
With an ever-growing test menu, the necessity of excellent two-way communication is essential. Unlike a routine G-banded chromosome analysis, each DNA assay and each FISH test is specific to a particular disease or disease category. On the other hand, today even a routine chromosome study requires us to understand whether you are looking for Down syndrome (PHA-stimulated lymphocyte culture), Pallister-Killian syndrome (skin fibroblast culture), acute leukemia (unstimulated culture of bone marrow), or CLL (B-cell mitogenized culture and FISH for trisomy 12). For this reason we will look for more opportunities to contribute to The Warde Report, and we ask you to bear with us in providing the relevant clinical information on the test requisition forms. In a cost-conscious era, we want to do the right test the first time, and any information you provide will be very much appreciated. We want to answer YOUR clinical question. Likewise telephone and email consultations are welcomed at any time.
Daniel L Van Dyke, Ph.D., FACMG
Chairman, Department of Medical Genetics
Director, Cytogenetics Laboratory