Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Shalini N. Jhangiani is active.

Publication


Featured researches published by Shalini N. Jhangiani.


Nature | 2008

Somatic mutations affect key pathways in lung adenocarcinoma

Li Ding; Gad Getz; David A. Wheeler; Elaine R. Mardis; Michael D. McLellan; Kristian Cibulskis; Carrie Sougnez; Heidi Greulich; Donna M. Muzny; Margaret Morgan; Lucinda Fulton; Robert S. Fulton; Qunyuan Zhang; Michael C. Wendl; Michael S. Lawrence; David E. Larson; Ken Chen; David J. Dooling; Aniko Sabo; Alicia Hawes; Hua Shen; Shalini N. Jhangiani; Lora Lewis; Otis Hall; Yiming Zhu; Tittu Mathew; Yanru Ren; Jiqiang Yao; Steven E. Scherer; Kerstin Clerc

Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers—including NF1, APC, RB1 and ATM—and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.


Nature | 2012

The Drosophila melanogaster Genetic Reference Panel

Trudy F. C. Mackay; Stephen Richards; Eric A. Stone; Antonio Barbadilla; Julien F. Ayroles; Dianhui Zhu; Sònia Casillas; Yi Han; Michael M. Magwire; Julie M. Cridland; Mark F. Richardson; Robert R. H. Anholt; Maite Barrón; Crystal Bess; Kerstin P. Blankenburg; Mary Anna Carbone; David Castellano; Lesley S. Chaboub; Laura H. Duncan; Zeke Harris; Mehwish Javaid; Joy Jayaseelan; Shalini N. Jhangiani; Katherine W. Jordan; Fremiet Lara; Faye Lawrence; Sandra L. Lee; Pablo Librado; Raquel S. Linheiro; Richard F. Lyman

A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype–phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype–phenotype mapping using the power of Drosophila genetics.


Proceedings of the National Academy of Sciences of the United States of America | 2012

Epistasis dominates the genetic architecture of Drosophila quantitative traits

Wen Huang; Stephen Richards; Mary Anna Carbone; Dianhui Zhu; Robert R. H. Anholt; Julien F. Ayroles; Laura H. Duncan; Katherine W. Jordan; Faye Lawrence; Michael M. Magwire; Crystal B. Warner; Kerstin P. Blankenburg; Yi Han; Mehwish Javaid; Joy Jayaseelan; Shalini N. Jhangiani; Donna M. Muzny; Fiona Ongeri; Lora Perales; Yuan Qing Wu; Yiqing Zhang; Xiaoyan Zou; Eric A. Stone; Richard A. Gibbs; Trudy F. C. Mackay

Epistasis—nonlinear genetic interactions between polymorphic loci—is the genetic basis of canalization and speciation, and epistatic interactions can be used to infer genetic networks affecting quantitative traits. However, the role that epistasis plays in the genetic architecture of quantitative traits is controversial. Here, we compared the genetic architecture of three Drosophila life history traits in the sequenced inbred lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) and a large outbred, advanced intercross population derived from 40 DGRP lines (Flyland). We assessed allele frequency changes between pools of individuals at the extremes of the distribution for each trait in the Flyland population by deep DNA sequencing. The genetic architecture of all traits was highly polygenic in both analyses. Surprisingly, none of the SNPs associated with the traits in Flyland replicated in the DGRP and vice versa. However, the majority of these SNPs participated in at least one epistatic interaction in the DGRP. Despite apparent additive effects at largely distinct loci in the two populations, the epistatic interactions perturbed common, biologically plausible, and highly connected genetic networks. Our analysis underscores the importance of epistasis as a principal factor that determines variation for quantitative traits and provides a means to uncover genetic networks affecting these traits. Knowledge of epistatic networks will contribute to our understanding of the genetic basis of evolutionarily and clinically important traits and enhance predictive ability at an individualized level in medicine and agriculture.


American Journal of Human Genetics | 2015

The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities

Jessica X. Chong; Kati J. Buckingham; Shalini N. Jhangiani; Corinne D. Boehm; Nara Sobreira; Joshua D. Smith; Tanya M. Harrell; Margaret J. McMillin; Wojciech Wiszniewski; Tomasz Gambin; Zeynep Coban Akdemir; Kimberly F. Doheny; Alan F. Scott; Dimitri Avramopoulos; Aravinda Chakravarti; Julie Hoover-Fong; Debra J. H. Mathews; P. Dane Witmer; Hua Ling; Kurt N. Hetrick; Lee Watkins; Karynne E. Patterson; Frederic Reinier; Elizabeth Blue; Donna M. Muzny; Martin Kircher; Kaya Bilguvar; Francesc López-Giráldez; V. Reid Sutton; Holly K. Tabor

Discovering the genetic basis of a Mendelian phenotype establishes a causal link between genotype and phenotype, making possible carrier and population screening and direct diagnosis. Such discoveries also contribute to our knowledge of gene function, gene regulation, development, and biological mechanisms that can be used for developing new therapeutics. As of February 2015, 2,937 genes underlying 4,163 Mendelian phenotypes have been discovered, but the genes underlying ∼50% (i.e., 3,152) of all known Mendelian phenotypes are still unknown, and many more Mendelian conditions have yet to be recognized. This is a formidable gap in biomedical knowledge. Accordingly, in December 2011, the NIH established the Centers for Mendelian Genomics (CMGs) to provide the collaborative framework and infrastructure necessary for undertaking large-scale whole-exome sequencing and discovery of the genetic variants responsible for Mendelian phenotypes. In partnership with 529 investigators from 261 institutions in 36 countries, the CMGs assessed 18,863 samples from 8,838 families representing 579 known and 470 novel Mendelian phenotypes as of January 2015. This collaborative effort has identified 956 genes, including 375 not previously associated with human health, that underlie a Mendelian phenotype. These results provide insight into study design and analytical strategies, identify novel mechanisms of disease, and reveal the extensive clinical variability of Mendelian phenotypes. Discovering the gene underlying every Mendelian phenotype will require tackling challenges such as worldwide ascertainment and phenotypic characterization of families affected by Mendelian conditions, improvement in sequencing and analytical techniques, and pervasive sharing of phenotypic and genomic data among researchers, clinicians, and families.


Science | 2014

The sheep genome illuminates biology of the rumen and lipid metabolism

Yu Jiang; Min Xie; Wenbin Chen; Richard Talbot; J. F. Maddox; Thomas Faraut; Chunhua Wu; Donna M. Muzny; Yuxiang Li; Wenguang Zhang; Jo-Ann L. Stanton; Rudiger Brauning; Wesley C. Barris; Thibaut Hourlier; Bronwen Aken; Stephen M. J. Searle; David L. Adelson; Chao Bian; Graham R. Cam; Yulin Chen; Shifeng Cheng; Udaya DeSilva; Karen Dixen; Yang Dong; Guangyi Fan; Ian R. Franklin; Shaoyin Fu; Pablo Fuentes-Utrilla; Rui Guan; Margaret A. Highland

A genome for ewe and ewe Sheep-specific genetic changes underlie differences in lipid metabolism between sheep and other mammals, and may have contributed to the production of wool. Jiang et al. sequenced the genome of two Texel sheep, a breed that produces high-value meat, milk, and wool. The genome information will provide an important resource for livestock production and aid in the understanding of mammalian evolution. Science, this issue p. 1168 A genomic analysis of sheep explains specializations in digestive system physiology and wool production. Sheep (Ovis aries) are a major source of meat, milk, and fiber in the form of wool and represent a distinct class of animals that have a specialized digestive organ, the rumen, that carries out the initial digestion of plant material. We have developed and analyzed a high-quality reference sheep genome and transcriptomes from 40 different tissues. We identified highly expressed genes encoding keratin cross-linking proteins associated with rumen evolution. We also identified genes involved in lipid metabolism that had been amplified and/or had altered tissue expression patterns. This may be in response to changes in the barrier lipids of the skin, an interaction between lipid metabolism and wool synthesis, and an increased role of volatile fatty acids in ruminants compared with nonruminant animals.


Cell | 2014

A drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases.

Shinya Yamamoto; Manish Jaiswal; Wu Lin Charng; Tomasz Gambin; Ender Karaca; Ghayda M. Mirzaa; Wojciech Wiszniewski; Hector Sandoval; Nele A. Haelterman; Bo Xiong; Ke Zhang; Vafa Bayat; Gabriela David; Tongchao Li; Kuchuan Chen; Upasana Gala; Tamar Harel; Davut Pehlivan; Samantha Penney; Lisenka E.L.M. Vissers; Joep de Ligt; Shalini N. Jhangiani; Yajing Xie; Stephen H. Tsang; Yesim Parman; Merve Sivaci; Esra Battaloglu; Donna M. Muzny; Ying Wooi Wan; Zhandong Liu

Invertebrate model systems are powerful tools for studying human disease owing to their genetic tractability and ease of screening. We conducted a mosaic genetic screen of lethal mutations on the Drosophila X chromosome to identify genes required for the development, function, and maintenance of the nervous system. We identified 165 genes, most of whose function has not been studied in vivo. In parallel, we investigated rare variant alleles in 1,929 human exomes from families with unsolved Mendelian disease. Genes that are essential in flies and have multiple human homologs were found to be likely to be associated with human diseases. Merging the human data sets with the fly genes allowed us to identify disease-associated mutations in six families and to provide insights into microcephaly associated with brain dysgenesis. This bidirectional synergism between fly genetics and human genomics facilitates the functional annotation of evolutionarily conserved genes involved in human health.


Cell | 2014

Human CLP1 Mutations Alter tRNA Biogenesis, Affecting Both Peripheral and Central Nervous System Function

Ender Karaca; Stefan Weitzer; Davut Pehlivan; Hiroshi Shiraishi; Tasos Gogakos; Toshikatsu Hanada; Shalini N. Jhangiani; Wojciech Wiszniewski; Marjorie Withers; Ian M. Campbell; Serkan Erdin; Sedat Işıkay; Luis M. Franco; Claudia Gonzaga-Jauregui; Tomasz Gambin; Violet Gelowani; Jill V. Hunter; Gozde Yesil; Erkan Koparir; Sarenur Yilmaz; Miguel Brown; Daniel Briskin; Markus Hafner; Pavel Morozov; Thalia A. Farazi; Christian Bernreuther; Markus Glatzel; Siegfried Trattnig; Joachim Friske; Claudia Kronnerwetter

CLP1 is a RNA kinase involved in tRNA splicing. Recently, CLP1 kinase-dead mice were shown to display a neuromuscular disorder with loss of motor neurons and muscle paralysis. Human genome analyses now identified a CLP1 homozygous missense mutation (p.R140H) in five unrelated families, leading to a loss of CLP1 interaction with the tRNA splicing endonuclease (TSEN) complex, largely reduced pre-tRNA cleavage activity, and accumulation of linear tRNA introns. The affected individuals develop severe motor-sensory defects, cortical dysgenesis, and microcephaly. Mice carrying kinase-dead CLP1 also displayed microcephaly and reduced cortical brain volume due to the enhanced cell death of neuronal progenitors that is associated with reduced numbers of cortical neurons. Our data elucidate a neurological syndrome defined by CLP1 mutations that impair tRNA splicing. Reduction of a founder mutation to homozygosity illustrates the importance of rare variations in disease and supports the clan genomics hypothesis.


Cell Reports | 2015

Exome Sequence Analysis Suggests that Genetic Burden Contributes to Phenotypic Variability and Complex Neuropathy

Claudia Gonzaga-Jauregui; Tamar Harel; Tomasz Gambin; Maria Kousi; Laurie B. Griffin; Ludmila Francescatto; Burcak Ozes; Ender Karaca; Shalini N. Jhangiani; Matthew N. Bainbridge; Kim Lawson; Davut Pehlivan; Yuji Okamoto; Marjorie Withers; Pedro Mancias; Anne Slavotinek; Pamela J. Reitnauer; Meryem Tuba Goksungur; Michael E. Shy; Thomas O. Crawford; Michel Koenig; Jason R. Willer; Brittany N. Flores; Igor Pediaditrakis; Onder Us; Wojciech Wiszniewski; Yesim Parman; Anthony Antonellis; Donna M. Muzny; Nicholas Katsanis

Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous distal symmetric polyneuropathy. Whole-exome sequencing (WES) of 40 individuals from 37 unrelated families with CMT-like peripheral neuropathy refractory to molecular diagnosis identified apparent causal mutations in ∼ 45% (17/37) of families. Three candidate disease genes are proposed, supported by a combination of genetic and in vivo studies. Aggregate analysis of mutation data revealed a significantly increased number of rare variants across 58 neuropathy-associated genes in subjects versus controls, confirmed in a second ethnically discrete neuropathy cohort, suggesting that mutation burden potentially contributes to phenotypic variability. Neuropathy genes shown to have highly penetrant Mendelizing variants (HPMVs) and implicated by burden in families were shown to interact genetically in a zebrafish assay exacerbating the phenotype established by the suppression of single genes. Our findings suggest that the combinatorial effect of rare variants contributes to disease burden and variable expressivity.


Journal of the National Cancer Institute | 2015

Germline mutations in shelterin complex genes are associated with familial glioma

Matthew N. Bainbridge; Georgina Armstrong; M. Monica Gramatges; Alison A. Bertuch; Shalini N. Jhangiani; Harsha Doddapaneni; Lora Lewis; Joseph Tombrello; Spyros Tsavachidis; Yanhong Liu; Ali Jalali; Sharon E. Plon; Ching C. Lau; Donald W. Parsons; Elizabeth B. Claus; Jill S. Barnholtz-Sloan; Dora Il'yasova; Joellen M. Schildkraut; Francis Ali-Osman; Siegal Sadetzki; Christoffer Johansen; Richard S. Houlston; Robert B. Jenkins; Daniel H. Lachance; Sara H. Olson; Jonine L. Bernstein; Ryan Merrell; Margaret Wrensch; Kyle M. Walsh; Faith G. Davis

Gliomas are the most common brain tumor, with several histological subtypes of various malignancy grade. The genetic contribution to familial glioma is not well understood. Using whole exome sequencing of 90 individuals from 55 families, we identified two families with mutations in POT1 (p.G95C, p.E450X), a member of the telomere shelterin complex, shared by both affected individuals in each family and predicted to impact DNA binding and TPP1 binding, respectively. Validation in a separate cohort of 264 individuals from 246 families identified an additional mutation in POT1 (p.D617Efs), also predicted to disrupt TPP1 binding. All families with POT1 mutations had affected members with oligodendroglioma, a specific subtype of glioma more sensitive to irradiation. These findings are important for understanding the origin of glioma and could have importance for the future diagnostics and treatment of glioma.


Current Biology | 2015

A massive expansion of effector genes underlies gall-formation in the wheat pest Mayetiola destructor.

Chaoyang Zhao; Lucio Navarro Escalante; Hang Chen; Thiago R. Benatti; Jiaxin Qu; Sanjay Chellapilla; Robert M. Waterhouse; David Wheeler; Martin Andersson; Riyue Bao; Matthew Batterton; Susanta K. Behura; Kerstin P. Blankenburg; Doina Caragea; James C. Carolan; Marcus Coyle; Mustapha El-Bouhssini; Liezl Francisco; Markus Friedrich; Navdeep Gill; Tony Grace; Cornelis J. P. Grimmelikhuijzen; Yi Han; Frank Hauser; Nicolae Herndon; Michael Holder; Panagiotis Ioannidis; LaRonda Jackson; Mehwish Javaid; Shalini N. Jhangiani

Gall-forming arthropods are highly specialized herbivores that, in combination with their hosts, produce extended phenotypes with unique morphologies [1]. Many are economically important, and others have improved our understanding of ecology and adaptive radiation [2]. However, the mechanisms that these arthropods use to induce plant galls are poorly understood. We sequenced the genome of the Hessian fly (Mayetiola destructor; Diptera: Cecidomyiidae), a plant parasitic gall midge and a pest of wheat (Triticum spp.), with the aim of identifying genic modifications that contribute to its plant-parasitic lifestyle. Among several adaptive modifications, we discovered an expansive reservoir of potential effector proteins. Nearly 5% of the 20,163 predicted gene models matched putative effector gene transcripts present in the M. destructor larval salivary gland. Another 466 putative effectors were discovered among the genes that have no sequence similarities in other organisms. The largest known arthropod gene family (family SSGP-71) was also discovered within the effector reservoir. SSGP-71 proteins lack sequence homologies to other proteins, but their structures resemble both ubiquitin E3 ligases in plants and E3-ligase-mimicking effectors in plant pathogenic bacteria. SSGP-71 proteins and wheat Skp proteins interact in vivo. Mutations in different SSGP-71 genes avoid the effector-triggered immunity that is directed by the wheat resistance genes H6 and H9. Results point to effectors as the agents responsible for arthropod-induced plant gall formation.

Collaboration


Dive into the Shalini N. Jhangiani's collaboration.

Top Co-Authors

Avatar

James R. Lupski

Baylor College of Medicine

View shared research outputs
Top Co-Authors

Avatar

Donna M. Muzny

Baylor College of Medicine

View shared research outputs
Top Co-Authors

Avatar

Richard A. Gibbs

Baylor College of Medicine

View shared research outputs
Top Co-Authors

Avatar

Tomasz Gambin

Warsaw University of Technology

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Eric Boerwinkle

University of Texas Health Science Center at Houston

View shared research outputs
Top Co-Authors

Avatar

Ender Karaca

Baylor College of Medicine

View shared research outputs
Top Co-Authors

Avatar

Davut Pehlivan

Baylor College of Medicine

View shared research outputs
Top Co-Authors

Avatar

Yavuz Bayram

Baylor College of Medicine

View shared research outputs
Top Co-Authors

Avatar
Researchain Logo
Decentralizing Knowledge