Biology subjects

Harris, D. N.

Publications and source records attributed to Harris, D. N..

4 recordsLinked to original sources

bioRxiv2020

Phantom histories of misspecified pasts

AO_SCPLOWBSTRACTC_SCPLOWThe observation that even a tiny sample of genome sequences from a natural population contains a plethora of information about the history of the population has enticed researchers to use these data to fit complex demographic histories and make detailed inference about the changes a population has experienced through time. Unfortunately, the standard assumptions required to make these inferences are often violated by natural populations in such ways as to produce specious results. This paper examines two phenomena of particular concern: when a sample is drawn from a single sub-population of a larger meta-population these models infer a spurious recent population decline, and when a genome contains loci under weak or recessive purifying selection these models infer a spurious recent population expansion.

genomics↗

bioRxiv2019

Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program

Summary paragraphThe Trans-Omics for Precision Medicine (TOPMed) program seeks to elucidate the genetic architecture and disease biology of heart, lung, blood, and sleep disorders, with the ultimate goal of improving diagnosis, treatment, and prevention. The initial phases of the program focus on whole genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here, we describe TOPMed goals and design as well as resources and early insights from the sequence data. The resources include a variant browser, a genotype imputation panel, and sharing of genomic and phenotypic data via dbGaP. In 53,581 TOPMed samples, >400 million single-nucleotide and insertion/deletion variants were detected by alignment with the reference genome. Additional novel variants are detectable through assembly of unmapped reads and customized analysis in highly variable loci. Among the >400 million variants detected, 97% have frequency <1% and 46% are singletons. These rare variants provide insights into mutational processes and recent human evolutionary history. The nearly complete catalog of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and non-coding sequence variants to phenotypic variation. Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and extends the reach of nearly all genome-wide association studies to include variants down to ~0.01% in frequency.

genomics↗

bioRxiv2017

The Evolutionary Genomic Dynamics of Peruvians Before, During, and After the Inca Empire

Native Americans from the Amazon, Andes, and coast regions of South America have a rich cultural heritage, but have been genetically understudied leading to gaps in our knowledge of their genomic architecture and demographic history. Here, we sequenced 150 high-coverage and genotyped 130 genomes from Native American and mestizo populations in Peru. A majority of our samples possess greater than 90% Native American ancestry and demographic modeling reveals, consistent with a rapid peopling model of the Americas, that most of Peru was peopled approximately 12,000 years ago. While the Native American populations possessed distinct ancestral divisions, the mestizo groups were admixtures of multiple Native American communities which occurred before and during the Inca Empire. The mestizo communities also show Spanish introgression only after Peruvian Independence. Thus, we present a detailed model of the evolutionary dynamics which impacted the genomes of modern day Peruvians.

genomics↗

bioRxiv2017

Evolution of Hominin Polyunsaturated Fatty Acid Metabolism: From Africa to the New World

BackgroundThe metabolic conversion of dietary omega-3 and omega-6 18 carbon (18C) to long chain (> 20 carbon) polyunsaturated fatty acids (LC-PUFAs) is vital for human life. Fatty acid desaturase (FADS) 1 and 2 catalyze the rate-limiting steps in the biosynthesis of LC-PUFAs. The FADS region contains two haplotypes; ancestral and derived, where the derived haplotypes are associated with more efficient LC-PUFA biosynthesis and is nearly fixed in Africa. In addition, Native American populations appear to be nearly fixed for the lesser efficient ancestral haplotype, which could be a public health problem due to associated low LC-PUFA levels, while Eurasia is polymorphic. This haplotype frequency distribution is suggestive of archaic re-introduction of the ancestral haplotype to non-African populations or ancient polymorphism with differential selection patterns across the globe. Therefore, we tested the FADS region for archaic introgression or ancient polymorphism. We specifically addressed the genetic architecture of the FADS region in Native American populations to better understand this potential public health impact.\n\nResultsWe confirmed Native American ancestry is nearly fixed for the ancestral haplotype and is under positive selection. The ancestral haplotype frequency is also correlated to Siberian populations geographic location further suggesting the ancestral haplotype s role in cold weather adaptation and leading to the high haplotype frequency within Native American populations. We also find that the Neanderthal is more closely related to the derived haplotypes while the Denisovan clusters closer to the ancestral haplotypes. In addition, the derived haplotypes have a time to the most recent common ancestor of 688,474 years ago which is within the range of the modern-archaic hominin divergence.\n\nConclusionsThese results support an ancient polymorphism forming in the FADS gene region with differential selection pressures acting on the derived and ancestral haplotypes due to the old age of the derived haplotypes and the ancestral haplotype being under positive selection in Native American ancestry populations. Further, the near fixation of the less efficient ancestral haplotype in Native American ancestry suggests the need for future studies to explore the potential health risk of associated low LC-PUFA levels in Native American ancestry populations.

evolutionary biology↗