Browsing by Author "Johnson, Claire"

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    Comparison of Identity by Descent Detection Algorithms and their Implementation with Pedigrees
    (2022) Johnson, Claire; Mathieson, Sara
    In recent history, access to biological and genomic data (provided by DNA sequencing) has exponentially increased as more efficient technologies have been developed. Newer, more accurate algorithms for analyzing this data are in high demand: in particular, the search for relatedness amongst individuals in a population to detect deleterious mutations that predispose one to certain diseases. Genome-wide association studies (GWAS) search for these disease-causing mutations, and motivation for this thesis is to improve identification and tracing of these mutations. Identity by descent (IBD)—segments of DNA shared between individuals sharing a common ancestor—is a principle that can be used to detect genetic variants and estimate mutation rates (Zhou et al., 2020). Several algorithmic methods can be utilized to pinpoint regions of IBD in genomic data: GERMLINE (used for thread, an algorithm that can reconstruct the genomes of ancestors via tracing IBD segments back through a pedigree), hap-IBD, and templated positional Burrows-Wheeler transform (TPBWT) will be the main focal points of this thesis. These methods use different tactics to find IBD segments such as "seed-and-extend" of IBS regions—small, shared segments of nucleotides—as for hap-IBD and GERMLINE (Zhou et al., 2020), or using an improved PBWT and heuristic algorithm to stitch together the IBD segments in TPBWT. All methods struggle to control levels of error introduced through handling genomic data. False negative and false positive errors are nearly inescapable despite the best efforts of contemporary algorithms. Therefore, one might consider using a pedigree—a tree-like diagram depicting the relationships between several generations of family members—to reduce the likelihood of these errors. These pedigrees, armed with the ability to show true relatedness, can be applied to algorithmically determined IBD segments to check if the amount of IBD sharing between pairs of individuals is realistic given their genealogical relationship. A comparison between these IBD identification algorithms will provide insight into what methods will provide consistent results long-term as GWAS data continues to increase. The foremost of these algorithms could then be combined with pedigrees to further bolster accuracy and efficiency of IBD detection. We endeavor to determine what method can reliably compute IBD segments shared between individuals and how this method might be enhanced with pedigrees.
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    T. H. Morgan, Nettie M. Stevens, and the Trouble with Aphids
    (2022) Johnson, Claire; Davis, Gregory K. (Biologist)
    When one considers the greatest discoveries in the history of biology, one is naturally drawn to think of well-known model organisms, such as mice or Drosophila melanogaster, which have been the backbone for most contemporary discoveries. Yet, along the way, there have been many other organisms—marine and terrestrial—that have bolstered our understanding of genotype-by- environment interactions (called polyphenisms) and organismal development. Aphids are one of these organisms. Aphids are particularly interesting for their cyclically parthenogenetic lifecycle: phases of female-only asexual reproduction in spring and summer, and male and female sexual reproduction in winter. It appeared to many that the determination of sex was due to environmental factors such as temperature or nutritional supply. Thomas Hunt Morgan, Chair of Biology at Bryn Mawr College from 1891-1904, chose to study aphids and their close relatives because he thought they would provide evidence in his favor in a long-standing conflict regarding the chromosomal theory of sex determination to which he was opposed, instead believing that the cytoplasm was at the heart of heredity and development. In 1905, he encouraged his former Ph.D. student at Bryn Mawr, Nettie M. Stevens, to study aphid development—specifically, the production of males, asexual females, and sexual females. In 1906, Morgan studied the development of a close relative of aphids, phylloxerans. Both he and Stevens committed the same crucial oversight. What had been overlooked and how? The complex lifecycle and biology of aphids may be the culprit. In 1908 and 1909, respectively, Morgan and Stevens—prompted by the former—revisited their own previous works and corrected their oversights. The back-and-forth communication between Morgan and Stevens during their studies of phylloxerans and aphids, respectively, arguably primed Morgan to be able to accurately apply the concept of sex linkage to his discovery of the famous mutant, white-eyed fly. He came to accept the truth of the chromosomal theory of sex determination in Drosophila, the very theory he had vigorously opposed.