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Mallory Romanovitch

Bio: Mallory Romanovitch is an academic researcher. The author has contributed to research in topics: Genome-wide association study & Copy-number variation. The author has an hindex of 5, co-authored 6 publications receiving 12645 citations.

Papers
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Journal ArticleDOI
Adam Auton1, Gonçalo R. Abecasis2, David Altshuler3, Richard Durbin4  +514 moreInstitutions (90)
01 Oct 2015-Nature
TL;DR: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations, and has reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-generation sequencing, deep exome sequencing, and dense microarray genotyping.
Abstract: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.

12,661 citations

01 Oct 2015
TL;DR: The 1000 Genomes Project as mentioned in this paper provided a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations, and reported the completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole genome sequencing, deep exome sequencing and dense microarray genotyping.
Abstract: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.

3,247 citations

Journal ArticleDOI
Peter H. Sudmant1, Tobias Rausch, Eugene J. Gardner2, Robert E. Handsaker3, Robert E. Handsaker4, Alexej Abyzov5, John Huddleston1, Yan Zhang6, Kai Ye7, Goo Jun8, Goo Jun9, Markus His Yang Fritz, Miriam K. Konkel10, Ankit Malhotra, Adrian M. Stütz, Xinghua Shi11, Francesco Paolo Casale12, Jieming Chen6, Fereydoun Hormozdiari1, Gargi Dayama8, Ken Chen13, Maika Malig1, Mark Chaisson1, Klaudia Walter12, Sascha Meiers, Seva Kashin3, Seva Kashin4, Erik Garrison14, Adam Auton15, Hugo Y. K. Lam, Xinmeng Jasmine Mu3, Xinmeng Jasmine Mu6, Can Alkan16, Danny Antaki17, Taejeong Bae5, Eliza Cerveira, Peter S. Chines18, Zechen Chong13, Laura Clarke12, Elif Dal16, Li Ding7, S. Emery8, Xian Fan13, Madhusudan Gujral17, Fatma Kahveci16, Jeffrey M. Kidd8, Yu Kong15, Eric-Wubbo Lameijer19, Shane A. McCarthy12, Paul Flicek12, Richard A. Gibbs20, Gabor T. Marth14, Christopher E. Mason21, Androniki Menelaou22, Androniki Menelaou23, Donna M. Muzny24, Bradley J. Nelson1, Amina Noor17, Nicholas F. Parrish25, Matthew Pendleton24, Andrew Quitadamo11, Benjamin Raeder, Eric E. Schadt24, Mallory Romanovitch, Andreas Schlattl, Robert Sebra24, Andrey A. Shabalin26, Andreas Untergasser27, Jerilyn A. Walker10, Min Wang20, Fuli Yu20, Chengsheng Zhang, Jing Zhang6, Xiangqun Zheng-Bradley12, Wanding Zhou13, Thomas Zichner, Jonathan Sebat17, Mark A. Batzer10, Steven A. McCarroll4, Steven A. McCarroll3, Ryan E. Mills8, Mark Gerstein6, Ali Bashir24, Oliver Stegle12, Scott E. Devine2, Charles Lee28, Evan E. Eichler1, Jan O. Korbel12 
01 Oct 2015-Nature
TL;DR: In this paper, the authors describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which are constructed using short-read DNA sequencing data and statistically phased onto haplotype blocks in 26 human populations.
Abstract: Structural variants are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which we constructed using short-read DNA sequencing data and statistically phased onto haplotype blocks in 26 human populations. Analysing this set, we identify numerous gene-intersecting structural variants exhibiting population stratification and describe naturally occurring homozygous gene knockouts that suggest the dispensability of a variety of human genes. We demonstrate that structural variants are enriched on haplotypes identified by genome-wide association studies and exhibit enrichment for expression quantitative trait loci. Additionally, we uncover appreciable levels of structural variant complexity at different scales, including genic loci subject to clusters of repeated rearrangement and complex structural variants with multiple breakpoints likely to have formed through individual mutational events. Our catalogue will enhance future studies into structural variant demography, functional impact and disease association.

1,971 citations

Journal ArticleDOI
TL;DR: A calibrated phylogenetic tree is constructed on the basis of binary single-nucleotide variants and the more complex variants onto it, estimating the number of mutations for each class and shows bursts of extreme expansion in male numbers that have occurred independently among the five continental superpopulations examined.
Abstract: We report the sequences of 1,244 human Y chromosomes randomly ascertained from 26 worldwide populations by the 1000 Genomes Project. We discovered more than 65,000 variants, including single-nucleotide variants, multiple-nucleotide variants, insertions and deletions, short tandem repeats, and copy number variants. Of these, copy number variants contribute the greatest predicted functional impact. We constructed a calibrated phylogenetic tree on the basis of binary single-nucleotide variants and projected the more complex variants onto it, estimating the number of mutations for each class. Our phylogeny shows bursts of extreme expansion in male numbers that have occurred independently among each of the five continental superpopulations examined, at times of known migrations and technological innovations.

280 citations

Book ChapterDOI
TL;DR: A microarray method is described that has been used for the detection of genome-wide CNVs, loss of heterozygosity (LOH), and uniparental disomy (UPD) associated with constitutional and neoplastic disorders.
Abstract: Copy number variations (CNVs) in the genomes have been suggested to play important roles in human evolution, genetic diversity, and disease susceptibility. A number of assays have been developed for the detection of CNVs, including fluorescent in situ hybridization (FISH), array-based comparative genomic hybridization (aCGH), PCR-based assays, and next-generation sequencing (NGS). In this chapter, we describe a microarray method that has been used for the detection of genome-wide CNVs, loss of heterozygosity (LOH), and uniparental disomy (UPD) associated with constitutional and neoplastic disorders.

7 citations


Cited by
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Journal ArticleDOI
Adam Auton1, Gonçalo R. Abecasis2, David Altshuler3, Richard Durbin4  +514 moreInstitutions (90)
01 Oct 2015-Nature
TL;DR: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations, and has reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-generation sequencing, deep exome sequencing, and dense microarray genotyping.
Abstract: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.

12,661 citations

Journal ArticleDOI
Monkol Lek, Konrad J. Karczewski1, Konrad J. Karczewski2, Eric Vallabh Minikel2, Eric Vallabh Minikel1, Kaitlin E. Samocha, Eric Banks1, Timothy Fennell1, Anne H. O’Donnell-Luria3, Anne H. O’Donnell-Luria2, Anne H. O’Donnell-Luria1, James S. Ware, Andrew J. Hill4, Andrew J. Hill2, Andrew J. Hill1, Beryl B. Cummings2, Beryl B. Cummings1, Taru Tukiainen2, Taru Tukiainen1, Daniel P. Birnbaum1, Jack A. Kosmicki, Laramie E. Duncan2, Laramie E. Duncan1, Karol Estrada1, Karol Estrada2, Fengmei Zhao1, Fengmei Zhao2, James Zou1, Emma Pierce-Hoffman1, Emma Pierce-Hoffman2, Joanne Berghout5, David Neil Cooper6, Nicole A. Deflaux7, Mark A. DePristo1, Ron Do, Jason Flannick2, Jason Flannick1, Menachem Fromer, Laura D. Gauthier1, Jackie Goldstein2, Jackie Goldstein1, Namrata Gupta1, Daniel P. Howrigan1, Daniel P. Howrigan2, Adam Kiezun1, Mitja I. Kurki2, Mitja I. Kurki1, Ami Levy Moonshine1, Pradeep Natarajan, Lorena Orozco, Gina M. Peloso1, Gina M. Peloso2, Ryan Poplin1, Manuel A. Rivas1, Valentin Ruano-Rubio1, Samuel A. Rose1, Douglas M. Ruderfer8, Khalid Shakir1, Peter D. Stenson6, Christine Stevens1, Brett Thomas1, Brett Thomas2, Grace Tiao1, María Teresa Tusié-Luna, Ben Weisburd1, Hong-Hee Won9, Dongmei Yu, David Altshuler10, David Altshuler1, Diego Ardissino, Michael Boehnke11, John Danesh12, Stacey Donnelly1, Roberto Elosua, Jose C. Florez2, Jose C. Florez1, Stacey Gabriel1, Gad Getz1, Gad Getz2, Stephen J. Glatt13, Christina M. Hultman14, Sekar Kathiresan, Markku Laakso15, Steven A. McCarroll2, Steven A. McCarroll1, Mark I. McCarthy16, Mark I. McCarthy17, Dermot P.B. McGovern18, Ruth McPherson19, Benjamin M. Neale2, Benjamin M. Neale1, Aarno Palotie, Shaun Purcell8, Danish Saleheen20, Jeremiah M. Scharf, Pamela Sklar, Patrick F. Sullivan14, Patrick F. Sullivan21, Jaakko Tuomilehto22, Ming T. Tsuang23, Hugh Watkins16, Hugh Watkins17, James G. Wilson24, Mark J. Daly1, Mark J. Daly2, Daniel G. MacArthur1, Daniel G. MacArthur2 
18 Aug 2016-Nature
TL;DR: The aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC) provides direct evidence for the presence of widespread mutational recurrence.
Abstract: Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of predicted protein-truncating variants, with 72% of these genes having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human 'knockout' variants in protein-coding genes.

8,758 citations

Journal ArticleDOI
11 Oct 2018-Nature
TL;DR: Deep phenotype and genome-wide genetic data from 500,000 individuals from the UK Biobank is described, describing population structure and relatedness in the cohort, and imputation to increase the number of testable variants to 96 million.
Abstract: The UK Biobank project is a prospective cohort study with deep genetic and phenotypic data collected on approximately 500,000 individuals from across the United Kingdom, aged between 40 and 69 at recruitment. The open resource is unique in its size and scope. A rich variety of phenotypic and health-related information is available on each participant, including biological measurements, lifestyle indicators, biomarkers in blood and urine, and imaging of the body and brain. Follow-up information is provided by linking health and medical records. Genome-wide genotype data have been collected on all participants, providing many opportunities for the discovery of new genetic associations and the genetic bases of complex traits. Here we describe the centralized analysis of the genetic data, including genotype quality, properties of population structure and relatedness of the genetic data, and efficient phasing and genotype imputation that increases the number of testable variants to around 96 million. Classical allelic variation at 11 human leukocyte antigen genes was imputed, resulting in the recovery of signals with known associations between human leukocyte antigen alleles and many diseases.

4,489 citations

Journal ArticleDOI
12 Oct 2017-Nature
TL;DR: It is found that local genetic variation affects gene expression levels for the majority of genes, and inter-chromosomal genetic effects for 93 genes and 112 loci are identified, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.
Abstract: Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.

3,289 citations

Journal ArticleDOI
TL;DR: These and other strategies are providing researchers and clinicians a variety of tools to probe genomes in greater depth, leading to an enhanced understanding of how genome sequence variants underlie phenotype and disease.
Abstract: Since the completion of the human genome project in 2003, extraordinary progress has been made in genome sequencing technologies, which has led to a decreased cost per megabase and an increase in the number and diversity of sequenced genomes. An astonishing complexity of genome architecture has been revealed, bringing these sequencing technologies to even greater advancements. Some approaches maximize the number of bases sequenced in the least amount of time, generating a wealth of data that can be used to understand increasingly complex phenotypes. Alternatively, other approaches now aim to sequence longer contiguous pieces of DNA, which are essential for resolving structurally complex regions. These and other strategies are providing researchers and clinicians a variety of tools to probe genomes in greater depth, leading to an enhanced understanding of how genome sequence variants underlie phenotype and disease.

3,096 citations