Forward Genomics of a Complex Trait: Mammalian Basal Metabolic Rate

The significance and nature of basal metabolic rate, a metabolic parameter recorded under specific laboratory conditions, are contested among biologists. Although it was most likely important in the evolution of endothermy in mammals and is associated with many other traits inter-and intra-specifically, the specifics of its heritability and its genetic determinants are largely unknown. Two bioinformatics pipelines are available which can associate traits with their genetic correlates given only whole genomes and phenotypes for each animal. However, extant pipelines were created with binary traits in mind. This leaves a void in our ability to associate continuous traits such as basal metabolic rate with genetic regions that influence them. To fill this gap, I developed a technique to augment the existing forward genomics pipeline developed by Hiller et al.(2012)by repeatedly analyzing a continuous trait converted to a binary trait via increasing thresholds. The results of my analysis identified a list of genes that have changed more from a reconstructed ancestral state in high BMR than in low BMR mammals. However, the list of genes did not appear to be enriched for genes associated with any biological process, function, or component clearly related to metabolism. Applying these analyses to other continuous traits could provide context for whether this result is unique to BMR, which could make a statement on its lack of straightforward genetic underpinnings, or is a result of the limitations of the forward genomics pipeline

Population and subspecies diversity at mouse centromere satellites.

BACKGROUND: Mammalian centromeres are satellite-rich chromatin domains that execute conserved roles in kinetochore assembly and chromosome segregation. Centromere satellites evolve rapidly between species, but little is known about population-level diversity across these loci. RESULTS: We developed a k-mer based method to quantify centromere copy number and sequence variation from whole genome sequencing data. We applied this method to diverse inbred and wild house mouse (Mus musculus) genomes to profile diversity across the core centromere (minor) satellite and the pericentromeric (major) satellite repeat. We show that minor satellite copy number varies more than 10-fold among inbred mouse strains, whereas major satellite copy numbers span a 3-fold range. In contrast to widely held assumptions about the homogeneity of mouse centromere repeats, we uncover marked satellite sequence heterogeneity within single genomes, with diversity levels across the minor satellite exceeding those at the major satellite. Analyses in wild-caught mice implicate subspecies and population origin as significant determinants of variation in satellite copy number and satellite heterogeneity. Intriguingly, we also find that wild-caught mice harbor dramatically reduced minor satellite copy number and elevated satellite sequence heterogeneity compared to inbred strains, suggesting that inbreeding may reshape centromere architecture in pronounced ways. CONCLUSION: Taken together, our results highlight the power of k-mer based approaches for probing variation across repetitive regions, provide an initial portrait of centromere variation across Mus musculus, and lay the groundwork for future functional studies on the consequences of natural genetic variation at these essential chromatin domains

UNBIASED, K-MER BASED ANALYSIS OF DIFFERENTIALLY PRESENT REPETITIVE ELEMENTS BETWEEN MOUSE SPECIES

Repetitive DNA elements have previously been considered junk DNA because they are not protein coding, but there is increasing evidence that many have impacts on the organisms that they inhabit. In this project, we manipulated tables of DNA k-mer frequencies for 59 diverse mouse genomes to reveal which k-mers varied most in frequency between genomes. This analysis revealed sets of differentially present, highly abundant k-mers that could be assembled into longer sequences. One sequence, seq A. had a number of notable attributes, such as an inverse repeat structure and consistent pattern of presence inside of known transposable elements. We began exploring these sequences to reveal routes for future study conducted a PCR consistent with the differential presence of seq A between mouse strains in vitro

Clustering Size Measurements of Extinct and Extant Bird Species

In this repository I perform clustering of size measurements of bird species, of which 469 were driven to extinction by humans