Small chromosomal structural variants are detected by the meiotic machinery in C. elegans
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Jakubik, Mattew Edward
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CitationJakubik, Mattew Edward. 2021. Small chromosomal structural variants are detected by the meiotic machinery in C. elegans. Doctoral dissertation, Harvard University Graduate School of Arts and Sciences.
AbstractHeterozygous chromosomal structural variants are widely present in many different organisms. These variants exist in many different forms, including copy number variants, insertions, deletions, and translocations and can be present in both homozygous and heterozygous forms. The widespread nature of structural variation begs the question as to what happens to heterozygous structural variants when homologous chromosomes pair during meiosis and if pairing could allow the genome to detect the presence of heterozygous variants. Here, we investigated whether homolog pairing during meiosis allows for the detection of heterozygous deficiencies in C. elegans. By determining Rad51 levels and kinetics in 28 heterozygous deficiency strains and 7 control strains, we demonstrate that heterozygous deficiencies as small as 34kb and as large as 2647kb displayed elevated Rad51 levels during meiotic prophase I and are, therefore, detected by the meiotic machinery. We also find a rough positive correlation between deficiency size and Rad51 response. We further demonstrate that many heterozygous deficiency strains show increased levels of leptotene-zygotene nuclei in early pachytene. This type of delay has previously been associated with the presence of unsynapsed chromosomal regions during C. elegans meiosis. Additionally, we find that homozygous viable translocations and inversions show a reduced Rad51 response when homozygous compared to when heterozygous. Thus, we suggest that detection of heterozygous deficiencies is dependent on pairing of homologous chromosomes. Finally, we discuss the implications of these findings given the widespread nature of structural variants in the genomes of a wide array of organisms.
Citable link to this pagehttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37368310
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