Understanding synergy in genetic interactions

Pérez-Pérez, José Manuel; Candela, Héctor; Micol, José Luis

doi:10.1016/j.tig.2009.06.004

Cited by 127 publications

(111 citation statements)

References 88 publications

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“…It is therefore conceivable that single‐cause disease is rather rare while the concert action of multiple contingent factors may better explains many complexed conditions like PSIS 39.…”

Section: Discussionmentioning

confidence: 99%

Multi‐genic pattern found in rare type of hypopituitarism: a whole‐exome sequencing study of Han Chinese with pituitary stalk interruption syndrome

Guo

Wang

et al. 2017

J Cellular Molecular Medi

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Pituitary stalk interruption syndrome (PSIS) is a rare type of hypopituitarism manifesting various degrees of pituitary hormone deficiency. Although mutations have been identified in some familial cases, the underpinning mechanisms of sporadic patients with PSIS who are in a vast majority remain elusive, necessitating a comprehensive study using systemic approaches. We postulate that other genetic mechanisms may be responsible for the sporadic PSIS. To test this hypothesis, we conducted a study in 24 patients with PSIS of Han Chinese with no family history using whole‐exome sequencing (WES) and bioinformatic analysis. We identified a group of heterozygous mutations in 92% (22 of 24) of the patients, and these genes are mostly associated with Notch, Shh, Wnt signalling pathways. Importantly, 83% (20 of 24) of the patients had more than one mutation in those pathways suggesting synergy of compound mutations underpin the pathogenesis of sporadic PSIS.

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“…It is therefore conceivable that single‐cause disease is rather rare while the concert action of multiple contingent factors may better explains many complexed conditions like PSIS 39.…”

Section: Discussionmentioning

confidence: 99%

Multi‐genic pattern found in rare type of hypopituitarism: a whole‐exome sequencing study of Han Chinese with pituitary stalk interruption syndrome

Guo

Wang

et al. 2017

J Cellular Molecular Medi

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“…Over time, one of the duplicates may be lost or both duplicates may be retained and diverge in sequence and function, leading to subfunctionalization or neofunctionalization, with corresponding changes in the degree of genetic redundancy (Pickett and Meeks-Wagner, 1995;Briggs et al, 2006;Pérez-Pérez et al, 2009;Chen et al, 2010).…”

Section: Discussion Molecular Dissection Of Duplicate Gene Functionmentioning

confidence: 99%

“…Because redundancy is assessed by comparing differences in single and multiple mutants, conclusions regarding genetic redundancy are necessarily dependent on the nature of the phenotypic analysis performed (Pickett and Meeks-Wagner, 1995;Pérez-Pérez et al, 2009;Lloyd and Meinke, 2012).…”

Section: Redundancy Is Relativementioning

confidence: 99%

“…For example, in Arabidopsis, <10% of single-gene insertional mutants exhibit discernable phenotypes, largely due to genetic redundancy originating from duplication events (Bouché and Bouchez, 2001;Hanada et al, 2009a;Pérez-Pérez et al, 2009;Brady et al, 2011).…”

Section: Using Molecular Phenotypes To Define Gene Functionmentioning

confidence: 99%

“…However, this approach relies on the availability of mutants that exhibit observable differences in phenotype. Unfortunately, the majority of single-gene mutants lack detectable alterations, due to genetic redundancy, other compensatory mechanisms, or difficulties in phenotypic assessment, which limits the usefulness of a genetic approach for defining gene function (Pickett and Meeks-Wagner, 1995;Bouché and Bouchez, 2001;Hanada et al, 2009a;Pérez-Pérez et al, 2009;Lloyd and Meinke, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Tissue-Specific Profiling Reveals Transcriptome Alterations inArabidopsisMutants Lacking Morphological Phenotypes

et al. 2013

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Traditional genetic analysis relies on mutants with observable phenotypes. Mutants lacking visible abnormalities may nevertheless exhibit molecular differences useful for defining gene function. To examine this, we analyzed tissue-specific transcript profiles from Arabidopsis thaliana transcription factor gene mutants with known roles in root epidermis development, but lacking a single-gene mutant phenotype due to genetic redundancy. We discovered substantial transcriptional changes in each mutant, preferentially affecting root epidermal genes in a manner consistent with the known double mutant effects. Furthermore, comparing transcript profiles of single and double mutants, we observed remarkable variation in the sensitivity of target genes to the loss of one or both paralogous genes, including preferential effects on specific branches of the epidermal gene network, likely reflecting the pathways of paralog subfunctionalization during evolution. In addition, we analyzed the root epidermal transcriptome of the transparent testa glabra2 mutant to clarify its role in the network. These findings provide insight into the molecular basis of genetic redundancy and duplicate gene diversification at the level of a specific gene regulatory network, and they demonstrate the usefulness of tissue-specific transcript profiling to define gene function in mutants lacking informative visible changes in phenotype.

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Rapid Detection of Hormonal Involvement in Light Responses

Vandenbussche

2019

Methods in Molecular Biology

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Understanding synergy in genetic interactions

Cited by 127 publications

References 88 publications

Multi‐genic pattern found in rare type of hypopituitarism: a whole‐exome sequencing study of Han Chinese with pituitary stalk interruption syndrome

Multi‐genic pattern found in rare type of hypopituitarism: a whole‐exome sequencing study of Han Chinese with pituitary stalk interruption syndrome

Tissue-Specific Profiling Reveals Transcriptome Alterations inArabidopsisMutants Lacking Morphological Phenotypes

Rapid Detection of Hormonal Involvement in Light Responses

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