scispace - formally typeset
Search or ask a question
Author

Heather A. Lawson

Other affiliations: Pennsylvania State University
Bio: Heather A. Lawson is an academic researcher from Washington University in St. Louis. The author has contributed to research in topics: Quantitative trait locus & Adipose tissue. The author has an hindex of 19, co-authored 40 publications receiving 2976 citations. Previous affiliations of Heather A. Lawson include Pennsylvania State University.

Papers
More filters
Journal ArticleDOI
13 Apr 2007-Science
TL;DR: The genome sequence of an Indian-origin Macaca mulatta female is determined and compared with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families.
Abstract: The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.

1,297 citations

Journal ArticleDOI
Devin P. Locke1, LaDeana W. Hillier1, Wesley C. Warren1, Kim C. Worley2, Lynne V. Nazareth2, Donna M. Muzny2, Shiaw-Pyng Yang1, Zhengyuan Wang1, Asif T. Chinwalla1, Patrick Minx1, Makedonka Mitreva1, Lisa Cook1, Kim D. Delehaunty1, Catrina Fronick1, Heather Schmidt1, Lucinda Fulton1, Robert S. Fulton1, Joanne O. Nelson1, Vincent Magrini1, Craig Pohl1, Tina Graves1, Chris Markovic1, Andy Cree2, Huyen Dinh2, Jennifer Hume2, Christie Kovar2, Gerald R. Fowler2, Gerton Lunter3, Gerton Lunter4, Stephen Meader4, Andreas Heger4, Chris P. Ponting4, Tomas Marques-Bonet5, Tomas Marques-Bonet6, Can Alkan6, Lin Chen6, Ze Cheng6, Jeffrey M. Kidd6, Evan E. Eichler6, Evan E. Eichler7, Simon D. M. White8, Stephen M. J. Searle8, Albert J. Vilella9, Yuan Chen9, Paul Flicek9, Jian Ma10, Jian Ma11, Brian J. Raney10, Bernard B. Suh10, Richard Burhans12, Javier Herrero9, David Haussler10, Rui Faria13, Rui Faria5, Olga Fernando5, Olga Fernando14, Fleur Darré5, Domènec Farré5, Elodie Gazave5, Meritxell Oliva5, Arcadi Navarro5, Roberta Roberto15, Oronzo Capozzi15, Nicoletta Archidiacono15, Giuliano Della Valle16, Stefania Purgato16, Mariano Rocchi15, Miriam K. Konkel17, Jerilyn A. Walker17, Brygg Ullmer17, Mark A. Batzer17, Arian F.A. Smit18, Robert Hubley18, Claudio Casola19, Daniel R. Schrider19, Matthew W. Hahn19, Víctor Quesada20, Xose S. Puente20, Gonzalo R. Ordóñez20, Carlos López-Otín20, Tomas Vinar21, Brona Brejova21, Aakrosh Ratan12, Robert S. Harris12, Webb Miller12, Carolin Kosiol, Heather A. Lawson1, Vikas Taliwal22, André L. Martins22, Adam Siepel22, Arindam RoyChoudhury23, Xin Ma22, Jeremiah D. Degenhardt22, Carlos Bustamante24, Ryan N. Gutenkunst25, Thomas Mailund26, Julien Y. Dutheil26, Asger Hobolth26, Mikkel H. Schierup26, Oliver A. Ryder, Yuko Yoshinaga27, Pieter J. de Jong27, George M. Weinstock1, Jeffrey Rogers2, Elaine R. Mardis1, Richard A. Gibbs2, Richard K. Wilson1 
27 Jan 2011-Nature
TL;DR: The orang-utan species, Pongo abelii and Pongo pygmaeus, are the most phylogenetically distant great apes from humans, thereby providing an informative perspective on hominid evolution and a primate polymorphic neocentromere, found in both Pongo species are described.
Abstract: 'Orang-utan' is derived from a Malay term meaning 'man of the forest' and aptly describes the southeast Asian great apes native to Sumatra and Borneo. The orang-utan species, Pongo abelii (Sumatran) and Pongo pygmaeus (Bornean), are the most phylogenetically distant great apes from humans, thereby providing an informative perspective on hominid evolution. Here we present a Sumatran orang-utan draft genome assembly and short read sequence data from five Sumatran and five Bornean orang-utan genomes. Our analyses reveal that, compared to other primates, the orang-utan genome has many unique features. Structural evolution of the orang-utan genome has proceeded much more slowly than other great apes, evidenced by fewer rearrangements, less segmental duplication, a lower rate of gene family turnover and surprisingly quiescent Alu repeats, which have played a major role in restructuring other primate genomes. We also describe a primate polymorphic neocentromere, found in both Pongo species, emphasizing the gradual evolution of orang-utan genome structure. Orang-utans have extremely low energy usage for a eutherian mammal, far lower than their hominid relatives. Adding their genome to the repertoire of sequenced primates illuminates new signals of positive selection in several pathways including glycolipid metabolism. From the population perspective, both Pongo species are deeply diverse; however, Sumatran individuals possess greater diversity than their Bornean counterparts, and more species-specific variation. Our estimate of Bornean/Sumatran speciation time, 400,000 years ago, is more recent than most previous studies and underscores the complexity of the orang-utan speciation process. Despite a smaller modern census population size, the Sumatran effective population size (N(e)) expanded exponentially relative to the ancestral N(e) after the split, while Bornean N(e) declined over the same period. Overall, the resources and analyses presented here offer new opportunities in evolutionary genomics, insights into hominid biology, and an extensive database of variation for conservation efforts.

555 citations

Journal ArticleDOI
TL;DR: A non-uniform distribution of human genetic substructure is illustrated, an instructional and useful paradigm for education and research and strong correlations between inter-marker distance and both locus-specific FST levels and branch lengths are demonstrated.
Abstract: Understanding the nature of evolutionary relationships among persons and populations is important for the efficient application of genome science to biomedical research. We have analysed 8,525 autosomal single nucleotide polymorphisms (SNPs) in 84 individuals from four populations: African-American, European-American, Chinese and Japanese. Individual relationships were reconstructed using the allele sharing distance and the neighbour-joining tree making method. Trees show clear clustering according to population, with the root branching from the African-American clade. The African-American cluster is much less star-like than European-American and East Asian clusters, primarily because of admixture. Furthermore, on the East Asian branch, all ten Chinese individuals cluster together and all ten Japanese individuals cluster together. Using positional information, we demonstrate strong correlations between inter-marker distance and both locus-specific FST (the proportion of total variation due to differentiation) levels and branch lengths. Chromosomal maps of the distribution of locus-specific branch lengths were constructed by combining these data with other published SNP markers (total of 33,704 SNPs). These maps clearly illustrate a non-uniform distribution of human genetic substructure, an instructional and useful paradigm for education and research.

241 citations

Journal ArticleDOI
TL;DR: In this paper, the parent-of-origin-dependent gene expression associated with genomic imprinting has been characterized and evidence supporting its role in complex trait variation and approaches for identifying its molecular signatures.
Abstract: Parent-of-origin effects occur when the phenotypic effect of an allele depends on whether it is inherited from the mother or the father. Several phenomena can cause parent-of-origin effects, but the best characterized is parent-of-origin-dependent gene expression associated with genomic imprinting. The development of new mapping approaches applied to the growing abundance of genomic data has demonstrated that imprinted genes can be important contributors to complex trait variation. Therefore, to understand the genetic architecture and evolution of complex traits, including complex diseases and traits of agricultural importance, it is crucial to account for these parent-of-origin effects. Here, we discuss patterns of phenotypic variation associated with imprinting, evidence supporting its role in complex trait variation and approaches for identifying its molecular signatures.

219 citations

Journal ArticleDOI
TL;DR: The WashU Epigenome Browser is extended, which currently hosts thousands of epigenome and transcriptome data sets for multiple cell types, tissues, individuals and species, to support multiple types of long-range genome interaction data, consistent with the hypothesis that chromatin domains are stable across cell types but can have different epigenetic profiles in different cells.
Abstract: To the Editor : Eukar yotic chromosomes are a highly organized three-dimensional entity folded through a tightly regulated process1,2 with important functions that include bringing distal regulatory elements into the vicinity of their target gene promoters and arranging the chromosomes into distinct compartments3–6. Recent technological innovations, including chromosome conformation capture carbon copy (5C), Hi-C and chromatin interaction analysis by paired-end tag sequencing (ChIA-PET), have facilitated the discovery of chromosomal organization principles and folding architectures at unprecedented scales and resolution. Each technology also comes with corresponding computational tools7,8 to process and visualize its specific data type (Supplementary Note 1). However, visualizing and navigating long-range interaction data, as well as integrating these interactions with other epigenomics data, remains a much-desired capability and a daunting challenge9. We have extended the WashU Epigenome Browser10 (http:// epigenomegateway.wustl.edu/), which currently hosts thousands of epigenome and transcriptome data sets for multiple cell types, tissues, individuals and species, to support multiple types of long-range genome interaction data. This enables investigators to explore epigenomic data in the context of higher-order chromosomal domains and to generate multiple types of intuitive, publication-quality figures of interactions (see tutorial in Supplementary Note 2). In Figure 1 we display the histonemodification profile and long-range interaction data of two human cell lines (IMR90 and K562) side by side and note that regions can exhibit similar interaction patterns while showing different histone modifications (such as the boundary region between domains 1 and 2) (Supplementary Methods). These observations are consistent with the hypothesis that chromatin domains are stable across cell types but can have different epigenetic profiles in different cells. Genes within each domain are regulated epigenetically in a cell type– specific manner5. Integrating higherorder chromatin interaction data with other genomic data could potentially reveal novel insights about mechanisms underlying gene and genome regulation. Pairs of interacting regions can be joined by arcs (Fig. 1b)—a suitable representation for sparse interactions—as is common with ChIA-PET and sometimes found in 5C data sets, or they can be indicated by filled rectangles in a heat map (Fig. 1c) for dense interactions (as is typical for Hi-C and some regions in 5C data sets). Investigators can click on the arcs or heat-map cells to invoke a companion Browser panel (Supplementary Fig. 1), which displays epigenomic data over the distal interacting locus. This companion panel can be navigated independently, enabling comparison of data patterns of interacting loci in the same view. Thus, investigators can observe several loci that are distant in their genomic coordinates but are inferred to be spatially close to each other in the nucleus. Both the “arc” and “heat-map” modes display only interactions that are contained within the current browsing range while omitting interactions beyond the range. To visualize the complete set of interactions, investigators can invoke the “Circlet View” (Supplementary Fig. 2), in which the chromosomal axis curls to form a circle and interactions are displayed as arcs inside the circle. Investigators can choose to display a single chromosome or to include interacting chromosomes to achieve a wholegenome perspective of the interactions. Investigators can also toggle between “thin,” “full” or “density” mode for any data track (Supplementary Figs. 3–5). “Gene Set View” and genomic juxtaposition can be combined with the long-range interaction function to focus on the interaction events in a subregion of the genome (Fig. 1). An investigator’s own long-range interaction data can be displayed on the Browser via the custom track or Data Hub function. The Browser currently hosts over 100 genomewide chromatin interaction data sets for human, mouse and fly. We expect such data to become increasingly available, and the browser will be a helpful tool for exploring how eukaryotic genomes function as nonlinear systems.

213 citations


Cited by
More filters
28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal Article
TL;DR: For the next few weeks the course is going to be exploring a field that’s actually older than classical population genetics, although the approach it’ll be taking to it involves the use of population genetic machinery.
Abstract: So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to

9,847 citations

01 Aug 2000
TL;DR: Assessment of medical technology in the context of commercialization with Bioentrepreneur course, which addresses many issues unique to biomedical products.
Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

4,833 citations

01 Feb 2015
TL;DR: In this article, the authors describe the integrative analysis of 111 reference human epigenomes generated as part of the NIH Roadmap Epigenomics Consortium, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

4,409 citations

Journal ArticleDOI
TL;DR: ABySS (Assembly By Short Sequences), a parallelized sequence assembler, was developed and assembled 3.5 billion paired-end reads from the genome of an African male publicly released by Illumina, Inc, representing 68% of the reference human genome.
Abstract: Widespread adoption of massively parallel deoxyribonucleic acid (DNA) sequencing instruments has prompted the recent development of de novo short read assembly algorithms. A common shortcoming of the available tools is their inability to efficiently assemble vast amounts of data generated from large-scale sequencing projects, such as the sequencing of individual human genomes to catalog natural genetic variation. To address this limitation, we developed ABySS (Assembly By Short Sequences), a parallelized sequence assembler. As a demonstration of the capability of our software, we assembled 3.5 billion paired-end reads from the genome of an African male publicly released by Illumina, Inc. Approximately 2.76 million contigs > or =100 base pairs (bp) in length were created with an N50 size of 1499 bp, representing 68% of the reference human genome. Analysis of these contigs identified polymorphic and novel sequences not present in the human reference assembly, which were validated by alignment to alternate human assemblies and to other primate genomes.

3,483 citations