Ivan Adzhubei
Harvard University
Publications 26
#1Christopher A. Cassa (Brigham and Women's Hospital)H-Index: 18
#2Daniel M. Jordan (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 13
Last.Shamil R. Sunyaev (Brigham and Women's Hospital)H-Index: 67
view all 4 authors...
Introduction: Over 150,000 variants have been reported to cause Mendelian disease in the medical literature. It is still difficult to leverage this knowledge base in clinical practice as many reports lack strong statistical evidence or may include false associations. Clinical laboratories assess whether these variants (along with newly observed variants that are adjacent to these published ones) underlie clinical disorders. Materials and Methods: We measured whether citation data -- including jo...
#1Virginia Savova (Harvard University)H-Index: 16
#2Esther J. Pearl (MBL: Marine Biological Laboratory)H-Index: 6
Last.Leonid Peshkin (Harvard University)H-Index: 31
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We characterize the genetic diversity of Xenopus laevis strains using RNA-seq data and allele-specific analysis. This data provides a catalogue of coding variation, which can be used for improving the genomic sequence, as well as for better sequence alignment, probe design, and proteomic analysis. In addition, we paint a broad picture of the genetic landscape of the species by functionally annotating different classes of mutations with a well-established prediction tool (PolyPhen-2). Further, we...
1 CitationsSource
#1Ron DoH-Index: 39
#2Daniel J. BalickH-Index: 7
Last.David ReichH-Index: 109
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David Reich, Shamil Sunyaev and colleagues report an analysis of the per-genome accumulation of nonsynonymous substitutions across diverse pairs of human populations. They find no evidence for a higher load of deleterious mutations in non-Africans than in West Africans and show that the observed patterns are not likely to reflect changes in natural selection.
108 CitationsSource
#1Ron Do (Harvard University)H-Index: 39
#2Daniel J. Balick (Brigham and Women's Hospital)H-Index: 7
Last.David Reich (Harvard University)H-Index: 109
view all 6 authors...
Non-African populations have experienced major bottlenecks in the time since their split from West Africans, which has led to the hypothesis that natural selection to remove weakly deleterious mutations may have been less effective in non-Africans. To directly test this hypothesis, we measure the per-genome accumulation of deleterious mutations across diverse humans. We fail to detect any significant differences, but find that archaic Denisovans accumulated non-synonymous mutations at a higher r...
6 CitationsSource
#1Ivan Adzhubei (Brigham and Women's Hospital)H-Index: 15
#2Daniel M. Jordan (Harvard University)H-Index: 13
Last.Shamil R. Sunyaev (Brigham and Women's Hospital)H-Index: 67
view all 3 authors...
PolyPhen-2 (Polymorphism Phenotyping v2), available as software and via a Web server, predicts the possible impact of amino acid substitutions on the stability and function of human proteins using structural and comparative evolutionary considerations. It performs functional annotation of single-nucleotide polymorphisms (SNPs), maps coding SNPs to gene transcripts, extracts protein sequence annotations and structural attributes, and builds conservation profiles. It then estimates the probability...
1,048 CitationsSource
#1Ignaty Leshchiner (Harvard University)H-Index: 20
#2Kristen Alexa (Harvard University)H-Index: 7
Last.Shamil R. Sunyaev (MIT: Massachusetts Institute of Technology)H-Index: 67
view all 17 authors...
Genetic mapping of mutations in model systems has facilitated the identification of genes contributing to fundamental biological processes including human diseases. However, this approach has historically required the prior characterization of informative markers. Here we report a fast and cost-effective method for genetic mapping using next-generation sequencing that combines single nucleotide polymorphism discovery, mutation localization, and potential identification of causal sequence variant...
82 CitationsSource
#1Ivan Adzhubei (Brigham and Women's Hospital)H-Index: 15
#2Steffen Schmidt (MPG: Max Planck Society)H-Index: 28
Last.Shamil R. Sunyaev (Brigham and Women's Hospital)H-Index: 67
view all 8 authors...
To the Editor: Applications of rapidly advancing sequencing technologies exacerbate the need to interpret individual sequence variants. Sequencing of phenotyped clinical subjects will soon become a method of choice in studies of the genetic causes of Mendelian and complex diseases. New exon capture techniques will direct sequencing efforts towards the most informative and easily interpretable protein-coding fraction of the genome. Thus, the demand for computational predictions of the impact of p...
7,131 CitationsSource
#1John A. Stamatoyannopoulos (UW: University of Washington)H-Index: 80
#2Ivan Adzhubei (Brigham and Women's Hospital)H-Index: 15
Last.Shamil R. Sunyaev (Brigham and Women's Hospital)H-Index: 67
view all 6 authors...
Eukaryotic DNA replication is highly stratified, with different genomic regions shown to replicate at characteristic times during S phase. Here we observe that mutation rate, as reflected in recent evolutionary divergence and human nucleotide diversity, is markedly increased in later-replicating regions of the human genome. All classes of substitutions are affected, suggesting a generalized mechanism involving replication time-dependent DNA damage. This correlation between mutation rate and regi...
279 CitationsSource
#1Steffen SchmidtH-Index: 28
#2Anna GerasimovaH-Index: 12
Last.Shamil R. SunyaevH-Index: 67
view all 6 authors...
The fourth author's name was spelled incorrectly. The correct name is: Ivan A. Adzhubei. The correct citation is: Schmidt S, Gerasimova A, Kondrashov FA, Adzhubei IA, Kondrashov AS, et al. (2008) Hypermutable Non-Synonymous Sites Are under Stronger Negative Selection. PLoS Genet 4(11): e1000281. doi:10.1371/journal.pgen.1000281
4 CitationsSource
#1Steffen Schmidt (MPG: Max Planck Society)H-Index: 28
#2Anna Gerasimova (UM: University of Michigan)H-Index: 12
Last.Shamil R. Sunyaev (Brigham and Women's Hospital)H-Index: 67
view all 6 authors...
Mutation rate varies greatly between nucleotide sites of the human genome and depends both on the global genomic location and the local sequence context of a site. In particular, CpG context elevates the mutation rate by an order of magnitude. Mutations also vary widely in their effect on the molecular function, phenotype, and fitness. Independence of the probability of occurrence of a new mutation's effect has been a fundamental premise in genetics. However, highly mutable contexts may be prese...
25 CitationsSource