[
International Worm Meeting,
2019]
When cells divide each daughter cell gets a chromosome set. However, the process is imperfect and occasionally chromosomes fail to separate, generating a nondisjunction event. Nondisjunction events can lead to aneuploidy and genetic instability, the former a hallmark of cancer in somatic cells. If nondisjunction occurs during gametogenesis, and the aneuploid gametes become part of a zygote, the resulting embryo has a high probability to abort or to develop physical or mental abnormalities such as human chromosome-21 trisomy, and Turner syndrome, in which females have only one X chromosome. Studying nondisjunction can give us a better understanding of how nondisjunction events occur, and could allow us to predict and alleviate some of its consequences. Our work aims to understand how chromosome nondisjunction is regulated, specifically, how genetic variation and stress influences the rates of chromosome-X nondisjunction. We leverage C. elegans sex determination system to study nondisjunction. Nondisjunction can produce chromosome X-depleted gametes, which upon fertilization form single-X embryos that will give rise to males. Thus, starting with a hermaphrodite population, the percentage of males over one generation is a proxy of chromosome-X nondisjunction rates. We can also increase the proportion of male progeny by subjecting hermaphrodites to stress. To map genetic variants affecting the rate of chromosome-X nondisjunction, we are using a panel of 359 Recombinant Inbred Lines (RILs). This RIL panel was built by mating the reference strain N2 with the CB4856 strain. N2 and CB4856 have different rates of chromosome-X nondisjunction. Thus far, we have phenotyped 90 strains. Preliminary analyses show that the trait is heritable, with genetic variation explaining 46% of the trait variance. An initial QTL mapping revealed that variants on chromosomes II and X might influence chromosome-X nondisjunction. We are currently testing a couple of candidate genes for the increase in chromosome-X nondisjunction.
[
International Worm Meeting,
2021]
The gut microbiome influences many of its host traits. In humans, disruption of the microbiota balance has been associated with various diseases including obesity, metabolic syndrome, and autoimmune disorders. However, it is challenging to study the mechanisms by which bacteria influence their human hosts due to the complexity of bacterial communities and the genetic diversity of humans. The nematode Caenorhabditis elegans has recently been used as a model organism to study the influence of the microbiome and diet on several phenotypes. Studies have shown that the worm microbiome/diet affects important traits such as development, life span, metabolism, and resistance to chemotherapy drugs, but the underlying mechanisms are not well understood. We recently discovered that resistance to cold stress in a related nematode, Caenorhabditis tropicalis, is affected by the worm diet. Interestingly, different C. tropicalis isolates are differently affected depending on their diet. Isolate JU1639 was highly susceptible to cold stress when grown on E. coli HT115 but survived when grown on OP50. Genetic analysis suggests that cold stress resistance is a dominant trait, and initial mapping reveled a potential QTL on chromosome III. Currently, we are working on refining and validating the QTL associated with cold stress resistance, and in dissecting the bacterial elements and pathways involved in the cold stress survival difference. The genetic variants uncovered by this study will further our understanding of the mechanisms by which diet and microbiome modulate an organism's phenotype, and how this modulation depends on the host genetic variation.