Genetic mutations you want

Williams, Sharon

doi:10.1073/pnas.1601663113

Cited by 8 publications

(5 citation statements)

References 17 publications

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“…The five nonsynonymous (C743A, G754T, C781A, C808G and T1173A) goat specific mutations we detected in the present study might despite the necessity of tested in larger population be valuable for future studies on the molecular and functional effect of mutations on differential prolificacy in Bangladeshi goat breeds. The molecular and functional effect of a mutation can be neutral, harmful or beneficial depending on their context or location (Williams, 2016). In our study, two of the identified polymorphisms (G754T and T1173A) predicted to have a significant effect on resulting protein sequences.…”

Section: Discussionmentioning

confidence: 73%

Polymorphism of fecundity genes (BMP15 and GDF9) and their association with litter size in Bangladeshi prolific Black Bengal goat

Das

Shaha

Gupta

et al. 2021

Trop Anim Health Prod

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Identification of prolificacy associated genetic markers remains vital in goat breeding industry since an increase in litter size can generate significant profit. Black Bengal is a prolific goat breed in Bangladesh. There are no inland reports on polymorphisms associated with fertility of Black Bengal goats in Bangladesh. In this study, we investigated two major fecundity genes-bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) in order to detect any possible mutations in these two genes in Bangladeshi Black Bengal goats. We identified six single nucleotide polymorphisms (SNP), of which five (C735A, C743A, G754T, C781A, and C808G) in BMP15 exon 2 and one (T1173A) in GDF9 exon 2. We also studied their association with litter size.Association analysis results show that polymorphism at the 735, 754 and 781 nucleotide positions of BMP15 exon 2 had significant association with litter size in Black Bengal goat. The effect of parity was also highly significant (p <0.001) on litter size. This study explored, for the first time, SNP loci in fecundity genes in Bangladeshi prolific Black Bengal goats. Further studies with a high number of genetically unrelated animals for assessing the association of these loci and others in the fecundity genes with litter size may be useful.

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Section: Discussionmentioning

confidence: 73%

Polymorphism of fecundity genes (BMP15 and GDF9) and their association with litter size in Bangladeshi prolific Black Bengal goat

Das

Shaha

Gupta

et al. 2021

Trop Anim Health Prod

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“…Studying human genetic disorders (Plenge et al, 2013; Nelson et al, 2015; Williams, 2016) in conjunction with knockout mice (Zambrowicz and Sands, 2003) can identify previously unknown tractable targets and lead to effective drugs. PCSK9 is an example of this strategy, as knowledge that human inactivating mutations result in hypocholesterolemia led to the development of neutralizing antibodies to treat this condition (Jaworski et al, 2017).…”

Section: Identifying Novel Drug Targetsmentioning

confidence: 99%

Predicting human disease mutations and identifying drug targets from mouse gene knockout phenotyping campaigns

Brommage

Powell

Vogel

2019

Disease Models &Amp; Mechanisms

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Two large-scale mouse gene knockout phenotyping campaigns have provided extensive data on the functions of thousands of mammalian genes. The ongoing International Mouse Phenotyping Consortium (IMPC), with the goal of examining all ∼20,000 mouse genes, has examined 5115 genes since 2011, and phenotypic data from several analyses are available on the IMPC website (www.mousephenotype.org). Mutant mice having at least one human genetic disease-associated phenotype are available for 185 IMPC genes. Lexicon Pharmaceuticals' Genome5000™ campaign performed similar analyses between 2000 and the end of 2008 focusing on the druggable genome, including enzymes, receptors, transporters, channels and secreted proteins. Mutants (4654 genes, with 3762 viable adult homozygous lines) with therapeutically interesting phenotypes were studied extensively. Importantly, phenotypes for 29 Lexicon mouse gene knockouts were published prior to observations of similar phenotypes resulting from homologous mutations in human genetic disorders. Knockout mouse phenotypes for an additional 30 genes mimicked previously published human genetic disorders. Several of these models have helped develop effective treatments for human diseases. For example, studying Tph1 knockout mice (lacking peripheral serotonin) aided the development of telotristat ethyl, an approved treatment for carcinoid syndrome. Sglt1 (also known as Slc5a1 ) and Sglt2 (also known as Slc5a2 ) knockout mice were employed to develop sotagliflozin, a dual SGLT1/SGLT2 inhibitor having success in clinical trials for diabetes. Clinical trials evaluating inhibitors of AAK1 (neuropathic pain) and SGLT1 (diabetes) are underway. The research community can take advantage of these unbiased analyses of gene function in mice, including the minimally studied ‘ignorome’ genes.

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“…The recent explosion of genomic data has allowed systematic searches for “fairy godmother” mutations or genetic variants that confer disease resistance (Williams, 2016). For example, recent work screened genomic sequence data from >589,000 subjects to identify 13 subjects with Mendelian disease causing mutations but without apparent disease.…”

Section: Other Diseasesmentioning

confidence: 99%

Informing Prevention and Intervention Policy Using Genetic Studies of Resistance

2016

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The common paradigm for conceptualizing the influence of genetic and environmental factors on a particular disease relies on the concept of risk. Consequently, the bulk of etiologic, including genetic, work focuses on "risk" factors. These factors are aggregated at the high end of the distribution of liability to disease, the latent variable underlying the distribution of probability and severity of a disorder. However, liability has a symmetric but distinct aspect to risk, resistance to disorder. Resistance factors, aggregated at the low end of the liability distribution and supporting health and recovery, appear to be more promising for effective prevention and intervention. Herein, we discuss existing work on resistance factors, highlighting those with known genetic influences. We examine the utility of incorporating resistance genetics in prevention and intervention trials and compare the statistical power of a series of ascertainment schemes to develop a general framework for examining resistance outcomes in genetically informative designs. We find that an approach that samples individuals discordant on measured liability, a low-risk design, is the most feasible design and yields power equivalent to or higher than commonly used designs for detecting resistance genetic and environmental effects.

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Genetic mutations you want

Cited by 8 publications

References 17 publications

Polymorphism of fecundity genes (BMP15 and GDF9) and their association with litter size in Bangladeshi prolific Black Bengal goat

Polymorphism of fecundity genes (BMP15 and GDF9) and their association with litter size in Bangladeshi prolific Black Bengal goat

Predicting human disease mutations and identifying drug targets from mouse gene knockout phenotyping campaigns

Informing Prevention and Intervention Policy Using Genetic Studies of Resistance

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