Using Down Syndrome (Trisomy 21) cells

to study chromosome organization

Presenter: Vanessa Sanchez

Co-Presenter(s):
Gabriel Quintero Plancarte

Presenter Status: Undergraduate student

Academic Year: 22-23

Semester: Spring

Faculty Mentor: Lisa Hua

Department: Biology

Funding Source/Sponsor: McNair

Other Funding Source/Program: LSAMP, Koret, Genentech, MESA, NSF, CSUPERB

Screenshot URL: https://drive.google.com/uc?id=1hXZLcJTUkugDXiYNr_-dNq7n8syikPcX

Abstract:
Genetic recombination is a key feature of meiosis, where the pairing of homologous chromosomes aids in creating four genetically unique haploid (1n) daughter cells [1]. However, recombination during mitosis leads to detrimental effects such as carcinogenesis, and genetic misregulation [2, 3]. To prevent/minimize the pairing of homologous chromosomes in mitosis, individual homologous autosomal and sex chromosomes spatially segregate, or antipair, along the centrosome axis [4]. Thus forming haploid sets on either side of the centrosome axis [4]. One possible mechanism underlying the haploid set segregation is parental origin. To test the parental origin of the haploid sets, we used male Trisomy 21 Down Syndrome (DS) fibroblast cells. The X and Y chromosomes were used as markers for the maternal and paternal genomes, respectively. The extra 21 chromosome was used as a maternal marker, as DS frequently arises from a nondisjunction event in maternal meiosis [5]. Using high resolution confocal microscopy, and chromosome painting for X, Y, and 21 our preliminary data reveals that the two chromosome 21 localizes in the X-containing hemisphere, and not in the Y-containing hemisphere. These results suggest that the haploid sets may be derived by parental origin, and may regulate the antiparing mechanisms between homologs. Findings of my project will allow us to improve our understanding of the mechanisms of human development and its implications in chromosomal disorders. 1. O'Connor, C. (2008) Meiosis, genetic recombination, and sexual reproduction. Nature Education 1(1):174 2. Gupta PK, et al. (1997) High frequency in vivo loss of heterozygosity is primarily a consequence of mitotic recombination. Cancer Res 57:1188–1193 3. Holt D, et al. (1999) Interindividual variation in mitotic recombination. Am J Hum Genet 65:1423–1427 4. Hua, L. L., & Mikawa, T. (2018). Mitotic antipairing of homologous and sex chromosomes via spatial restriction of two haploid sets. Proceedings of the National Academy of Sciences, 115(52). doi: 10.1073/pnas.1809583115 5. Hultén, M. A., Patel, S. D., Westgren, M., Papadogiannakis, N., Jonsson, A. M., Jonasson, J., & Iwarsson, E. (2010). On the paternal origin of trisomy 21 Down syndrome. Molecular cytogenetics, 3, 4. https://doi.org/10.1186/1755-8166-3-4