University of Kentucky
Comparing Differences in the Endpoint of Mutations Between Ancestry Groups
Grade Level at Time of Presentation
Sophomore
Major
Biology
Minor
Creative Writing
Institution 23-24
University of Kentucky
KY House District #
79
KY Senate District #
13
Faculty Advisor/ Mentor
Yasminka Jakubek Swartzlander, Ph.D.
Department
Dept. of Internal Medicine
Abstract
Differences across genetic ancestry groups have been observed in the rate and genomic location of somatic chromosomal alterations (mCAs) detected from sequencing of blood tissues from donors without cancer. This project sought to determine whether there are differences in the frequency of somatic copy number mutations that span entire chromosome arms compared to those with endpoints within a chromosome arm, which would indicate a double strand break during generation of the copy number change. A double strand break (DSB) occurs when the sugar-phosphate backbone of the DNA molecule is split between two neighboring nucleotides. This type of DNA damage can be caused by environmental agents such as ionizing radiation, ultraviolet light, chemical compounds, diet, smoking, and air pollution. The driving hypothesis behind this project is that differences in mutation rate, if present, stem from variations in DNA-damaging factors or genetic susceptibility across ancestry groups. Determination of differences in mutation frequency across European American (EA), African American (AA), and Hispanic American (HA) groups (clustered based on genetic similarity) was accomplished through the development of python scripts to identify breakpoints from somatic copy number changes. These were then sorted across two categories: Endpoint at chromosome arm boundaries and endpoint within the chromosome arm. The results of this analysis indicate that there are no differences across genetic ancestry groups in the frequency of inferred somatic copy number changes arising from double strand breaks. Our findings support the notion that genetic and environmental drivers do not lead to differences in DNA double strand breaks across these groups; however, further validation is warranted in additional cohorts.
Comparing Differences in the Endpoint of Mutations Between Ancestry Groups
Differences across genetic ancestry groups have been observed in the rate and genomic location of somatic chromosomal alterations (mCAs) detected from sequencing of blood tissues from donors without cancer. This project sought to determine whether there are differences in the frequency of somatic copy number mutations that span entire chromosome arms compared to those with endpoints within a chromosome arm, which would indicate a double strand break during generation of the copy number change. A double strand break (DSB) occurs when the sugar-phosphate backbone of the DNA molecule is split between two neighboring nucleotides. This type of DNA damage can be caused by environmental agents such as ionizing radiation, ultraviolet light, chemical compounds, diet, smoking, and air pollution. The driving hypothesis behind this project is that differences in mutation rate, if present, stem from variations in DNA-damaging factors or genetic susceptibility across ancestry groups. Determination of differences in mutation frequency across European American (EA), African American (AA), and Hispanic American (HA) groups (clustered based on genetic similarity) was accomplished through the development of python scripts to identify breakpoints from somatic copy number changes. These were then sorted across two categories: Endpoint at chromosome arm boundaries and endpoint within the chromosome arm. The results of this analysis indicate that there are no differences across genetic ancestry groups in the frequency of inferred somatic copy number changes arising from double strand breaks. Our findings support the notion that genetic and environmental drivers do not lead to differences in DNA double strand breaks across these groups; however, further validation is warranted in additional cohorts.