Dr Daniel Gaffney

Daniel's research combines computational and statistical methods with high-throughput experimental techniques to study eukaryotic gene regulation.

Daniel earned his PhD in evolutionary genetics from Edinburgh University in 2006 under the supervision of Dr Peter Keightley. His graduate research used computational methods to study variation in the mutation rate and natural selection in noncoding DNA. From 2006 to 2008 he pursued a postdoc with Dr Jacek Majewski in McGill University and Genome Quebec Genome Centre, where he worked on the evolution of transcriptional regulation in primates, and the role of alternative splicing in embryonic development. From 2008 until 2011 he worked on population genetic variation in gene expression and regulation with Dr Jonathan Pritchard at the University of Chicago.

In July 2011 Daniel started as a Career Development Fellowship Group Leader at the Wellcome Trust Sanger Institute. The long-term goal of the group is to understand how changes in gene regulation play a role in disease susceptibility and human evolution. His research combines statistical genetics and comparative genomics with high-throughput experimental techniques, such as ChIP-seq and DNaseI-seq, in human cells to address these questions. The group uses naturally occurring human genetic variation as a model system to test hypotheses about gene regulation. The team is also interested in developing evolutionary models of gene regulation to understand how changes at the molecular level drive gene expression divergence between species.

Selected Publications

• Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis.

  Liu JZ, Almarri MA, Gaffney DJ, Mells GF, Jostins L, Cordell HJ, Ducker SJ, Day DB, Heneghan MA, Neuberger JM, Donaldson PT, Bathgate AJ, Burroughs A, Davies MH, Jones DE, Alexander GJ, Barrett JC, Sandford RN, Anderson CA, UK Primary Biliary Cirrhosis (PBC) Consortium and Wellcome Trust Case Control Consortium 3

  Nature genetics 2012;44;10;1137-41

  PUBMED: 22961000; PMC: 3459817; DOI: 10.1038/ng.2395

• DNA sequence-dependent compartmentalization and silencing of chromatin at the nuclear lamina.

  Zullo JM, Demarco IA, Piqué-Regi R, Gaffney DJ, Epstein CB, Spooner CJ, Luperchio TR, Bernstein BE, Pritchard JK, Reddy KL and Singh H

  Cell 2012;149;7;1474-87

  PUBMED: 22726435; DOI: 10.1016/j.cell.2012.04.035

• DNase I sensitivity QTLs are a major determinant of human expression variation.

  Degner JF, Pai AA, Pique-Regi R, Veyrieras JB, Gaffney DJ, Pickrell JK, De Leon S, Michelini K, Lewellen N, Crawford GE, Stephens M, Gilad Y and Pritchard JK

  Nature 2012;482;7385;390-4

  PUBMED: 22307276; PMC: 3501342; DOI: 10.1038/nature10808

• The contribution of RNA decay quantitative trait loci to inter-individual variation in steady-state gene expression levels.

  Pai AA, Cain CE, Mizrahi-Man O, De Leon S, Lewellen N, Veyrieras JB, Degner JF, Gaffney DJ, Pickrell JK, Stephens M, Pritchard JK and Gilad Y

  PLoS genetics 2012;8;10;e1003000

  PUBMED: 23071454; PMC: 3469421; DOI: 10.1371/journal.pgen.1003000

• Controls of nucleosome positioning in the human genome.

  Gaffney DJ, McVicker G, Pai AA, Fondufe-Mittendorf YN, Lewellen N, Michelini K, Widom J, Gilad Y and Pritchard JK

  PLoS genetics 2012;8;11;e1003036

  PUBMED: 23166509; PMC: 3499251; DOI: 10.1371/journal.pgen.1003036

• Dissecting the regulatory architecture of gene expression QTLs.

  Gaffney DJ, Veyrieras JB, Degner JF, Pique-Regi R, Pai AA, Crawford GE, Stephens M, Gilad Y and Pritchard JK

  Genome biology 2012;13;1;R7

  PUBMED: 22293038; PMC: 3334587; DOI: 10.1186/gb-2012-13-1-r7

• Exon-specific QTLs skew the inferred distribution of expression QTLs detected using gene expression array data.

  Veyrieras JB, Gaffney DJ, Pickrell JK, Gilad Y, Stephens M and Pritchard JK

  PloS one 2012;7;2;e30629

  PUBMED: 22359548; PMC: 3281037; DOI: 10.1371/journal.pone.0030629

• False positive peaks in ChIP-seq and other sequencing-based functional assays caused by unannotated high copy number regions.

  Pickrell JK, Gaffney DJ, Gilad Y and Pritchard JK

  Bioinformatics (Oxford, England) 2011;27;15;2144-6

  PUBMED: 21690102; PMC: 3137225; DOI: 10.1093/bioinformatics/btr354

• Accurate inference of transcription factor binding from DNA sequence and chromatin accessibility data.

  Pique-Regi R, Degner JF, Pai AA, Gaffney DJ, Gilad Y and Pritchard JK

  Genome research 2011;21;3;447-55

  PUBMED: 21106904; PMC: 3044858; DOI: 10.1101/gr.112623.110

• DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines.

  Bell JT, Pai AA, Pickrell JK, Gaffney DJ, Pique-Regi R, Degner JF, Gilad Y and Pritchard JK

  Genome biology 2011;12;1;R10

  PUBMED: 21251332; PMC: 3091299; DOI: 10.1186/gb-2011-12-1-r10

• Alternative splicing is frequent during early embryonic development in mouse.

  Revil T, Gaffney D, Dias C, Majewski J and Jerome-Majewska LA

  BMC genomics 2010;11;399

  PUBMED: 20573213; PMC: 2898759; DOI: 10.1186/1471-2164-11-399

• Effect of the assignment of ancestral CpG state on the estimation of nucleotide substitution rates in mammals.

  Gaffney DJ and Keightley PD

  BMC evolutionary biology 2008;8;265

  PUBMED: 18826599; PMC: 2576242; DOI: 10.1186/1471-2148-8-265

• Selective constraints in experimentally defined primate regulatory regions.

  Gaffney DJ, Blekhman R and Majewski J

  PLoS genetics 2008;4;8;e1000157

  PUBMED: 18704158; PMC: 2490716; DOI: 10.1371/journal.pgen.1000157

• Genomic selective constraints in murid noncoding DNA.

  Gaffney DJ and Keightley PD

  PLoS genetics 2006;2;11;e204

  PUBMED: 17166057; PMC: 1657059; DOI: 10.1371/journal.pgen.0020204

• The scale of mutational variation in the murid genome.

  Gaffney DJ and Keightley PD

  Genome research 2005;15;8;1086-94

  PUBMED: 16024822; PMC: 1182221; DOI: 10.1101/gr.3895005

• Functional constraints and frequency of deleterious mutations in noncoding DNA of rodents.

  Keightley PD and Gaffney DJ

  Proceedings of the National Academy of Sciences of the United States of America 2003;100;23;13402-6

  PUBMED: 14597721; PMC: 263826; DOI: 10.1073/pnas.2233252100