Elucidating Gene Function with the use of Genome Wide Association Study (GWAS)

Abstract

DNA replication and cell proliferation are intensely studied subjects. There have been countless experiments and hours put into better understanding how DNA is replicated and compacted, and how cells are able to proliferate with this new DNA. While there have been many breakthroughs throughout history in these subjects, the progress has been at times, slow. Advancing technologies have made studying biological phenomena easier as time progresses. The mysteries that still surround life are being uncovered with new vigor and at hastening paces. With the advent of the genome-wide association study (GWAS), researchers are able to determine gene functions based off of the variation already present in life. By examining multitudes of specimens with slightly differing genetic makeups, researchers are able to deduce gene function from those slight variations. A small single nucleotide can have resounding effects on organisms, such as with sickle cell anemia, or Tay-Sachs; both diseases caused by only a single nucleotide being different from the norm, or point mutation. GWA studies work with a similar principle in mind. By looking at all single nucleotide polymorphisms (SNPs), we can deduce that any phenotypic changes observed in our specimens are caused by these slight changes in the genetic code. The Drosophila Genetic Reference Panel is a GWAS using the organism Drosophila melanogaster. This is a relatively new GWA, developed by Dr. Trudy McKay from NC State University (NCSU). Already there are over 200 strains that are genetically different from the others. By analyzing specific traits, known as quantitative traits, or traits which can be marked by a number, we can deduce what genetic factors could be playing a role in the traits observed. For this study, we will be observing DNA quantity for DNA replication, nucleus size with DNA quantity for DNA compaction, and nuclei counts for cell proliferation. By quantifying these traits for each strain, we will then be able to use the DGRP pipeline to uncover new genetic players in these traits. Some genes may have a role in all traits studied, some may only be involved in one, and some may not have a direct role at all, and only play an indirect regulatory role. While all of this is unknown at the moment, this study hopes to unveil the genetic players that have a high likelihood of being involved in one or more of these traits. Once these genetic markers have been unveiled, new studies can be done to specifically target these genes to allow for more concrete evidence to be provided in support of their roles in the studied traits.