Week 2: Cytogenetics and Late Night Talk Shows

This week in clinical genetics involved going to a cytogenetics laboratory which, for those of you who do not know, is the study of chromosome structure to develop hypotheses and conclusions about genetic function and patient outcomes. There is a slew of genetic disorders out there that are affected by chromosomal abnormalities ranging from extra chromosomes, missing chromosomes or swapping genetic information between different chromosomes (called translocations). For example, Down syndrome is a disorder caused by a trisomy 21. In layman’s terms, that means that someone with Down syndrome contains three copies of chromosome 21 as opposed to the normal two copies from both the mother and the father. This abnormality develops the classic features, developmental delays, and physical disabilities exhibited by individuals with this disorder. The big question here is how does anyone confirm these conditions are present, especially for pregnant women, older people with a higher risk of cancer, and people trying to have children.

My week in a cytogenetics laboratory elucidated some answers to the above question. A little outside the realm of direct clinical contact with patients, I arrived in a cytogenetics laboratory and got an extensive overview of the work they do there by the director. She talked about genetic disorders and some of the common ones they spot and the clinical outcomes of the results they deliver to doctors. More specifically, the p53 mutation that is well known to be associated with cancer and poor patient outcomes is one that often forms near the end of life for patients that this lab screens. The way that they perform these screens is through harvesting of a tissue biopsy (amniotic fluid from a pregnant woman, peripheral blood or bone marrow from a patient, etc.), culturing the cells for a certain amount of time to maximize the number of cells in metaphase (part of the cell cycle in mitosis that separates chromosomes for maximum accessibility visually), and permeabilizing cell and nuclear membranes such that the chromosomes can be exposed. These free chromosomes can then be stained so that they can be imaged by the lab technician for any abnormalities (this is called karyotyping).

Another method that cytogeneticists use that has more sensitivity is called fluorescence in situ hybridization aka FISH (the amount of fish puns I want to make here is significantly high, but I will spare you). The basic premise of FISH is using fluorescent DNA probes to map the locations of specific genes on the chromosomes in intact nuclei that clinically represent the cells inside the body. I was able to see firsthand some of the cases that required this procedure and how certain abnormalities tend to be present through the human population. Since genomes are so complicated and we have barely scratched the surface of genomic interactions, I was surprised to see the pattern of disease that seems to progress on the chromosomes. Also, colorful images are always nice to examine.

Beyond the clinical experiences, this week I delved into New York a little further and ventured out to Brooklyn. See an image below of the Brooklyn Bridge. It’s much better in person. I guarantee it. Also, to top the week off, I went to see the Late Show with Stephen Colbert! If you asked me a year ago, I would be in NYC doing all of this, I would think you are crazy!