A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly.

By L. Lettice, S. Heaney, Lorna A. Purdie, Li Li, P. D. De Beer, B. Oostra, D. Goode, G. Elgar, R. Hill, E. de Graaff. Human Molecular Genetics, 2003

1,222 citations recorded by the source corpus.

Subfields: Developmental Biology, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/f453163ef2b8303961b67c8b244160b0fe4321c6

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Citations in the corpus

Long-range control of gene expression: emerging mechanisms and disruption in disease. (2005, methodology): “Some examples have been identified, initially through mouse models (Lettice et al. 2003) or through detailed mapping and sequencing studies around a strong candidate gene (Enattah et al.”
Transcriptional enhancers: from properties to genome-wide predictions (2014, background): “The necessity and sufficiency of individual enhancers for gene expression in defined cell types or tissues is also supported by several known diseases that are related to specific enhancer mutations 113–115 (reviewed in REF.”
Ever-changing landscapes: transcriptional enhancers in development and evolution (2016, background): “Because of their developmental importance and strict structural requirements, mutations at conserved regulatory sites are also associated with human disease, as seen for the deeply conserved Shh enhancer that drives preaxial polydactyly upon disruption (Lettice et al., 2003).”
Needles in stacks of needles: finding disease-causal variants in a wealth of genomic data (2011, neutral): “Conversely, the existence of numerous large-effect regulatory variants 61–63 — despite the increased difficulties associated with their discovery — confirms at least that a substantial fraction of mutations underlying Mendelian diseases is non-coding.”
Hedgehog: functions and mechanisms. (2008, background): “Consistently in humans, germline mutations within the conserved MFCS1 element cause congenital limb malformations characterized by preaxial polydactyly (Lettice et al. 2003).”
Chromosome 21 and Down syndrome: from genomics to pathophysiology (2004, background): “A recent example of this comes from the duplication of ∼30 Kb containing a conserved regulatory element that maps ∼1 Mb from the sonic hedgehog ( Shh ) locus and causes PREAXIAL POLYDACTYLY in the sasquatch ( Ssq ) mouse mutan”
A computational pipeline for comparative ChIP-seq analyses (2011, background): “…however, as enhancers bound by transcription factors are able to activate their target genes from remote distances and even across nonregulated genes located in between (e.g., more than 1 Mb for the mouse gene Shh (encoding Sonic hedgehog) 20,21 ; see also shadow enhancers in Drosophila 22 ).”
Regulation of disease-associated gene expression in the 3D genome (2016, neutral): “Examples of such genes include Shh (encoding Sonic hedgehog) 35–37 , Myc (encoding the Myc protooncogene) 38 , Fgf8 (encoding fibroblast growth factor 8) 39 and the HOX 40,41 gene family.”