Intronic SNP in ESR1 encoding human estrogen receptor alpha is associated with brain ESR1 mRNA isoform expression and behavioral traits

Pinsonneault, Julia K.; Frater, John T.; Kompa, Benjamin; Mascarenhas, Roshan; Wang, Daqing; Sadée, Wolfgang

doi:10.1371/journal.pone.0179020

Cited by 14 publications

(11 citation statements)

References 51 publications

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“…Approximately 81% of the 13,748 SNPs in PCGs were annotated in potentially neutral regions (introns), while 19% were annotated in potentially functional regions (Table 6). Even considered as a potentially neutral region, SNPs in introns can be associated with the phenotype, playing a role in gene expression and alternative splicing regulation as well, affecting the mRNA transport, providing important information to understand the genetic architecture of the trait [71–73]. However, SNPs located in introns were not deeply investigated in this study.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association scan for QTL and their positional candidate genes associated with internal organ traits in chickens

et al. 2019

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Background Poultry breeding programs have been focused on improvement of growth and carcass traits, however, this has resulted in correlated changes in internal organ weights and increased incidence of metabolic disorders. These disorders can affect feed efficiency or even cause death. We used a high density SNP array (600 K, Affymetrix) to estimate genomic heritability, perform genome-wide association analysis, and identify genomic regions and positional candidate genes (PCGs) associated with internal organ traits in an F2 chicken population. We integrated knowledge of haplotype blocks, selection signature regions and sequencing data to refine the list of PCGs. Results Estimated genomic heritability for internal organ traits in chickens ranged from low (LUNGWT, 0.06) to high (GIZZWT, 0.45). A total of 20 unique 1 Mb windows identified on GGA1, 2, 4, 7, 12, 15, 18, 19, 21, 27 and 28 were significantly associated with intestine length, and weights or percentages of liver, gizzard or lungs. Within these windows, 14 PCGs were identified based on their biological functions: TNFSF11 , GTF2F2 , SPERT , KCTD4 , HTR2A , RB1 , PCDH7 , LCORL , LDB2 , NR4A2 , GPD2 , PTPN11 , ITGB4 and SLC6A4 . From those genes, two were located within haplotype blocks and three overlapped with selection signature regions. A total of 13,748 annotated sequence SNPs were in the 14 PCGs, including 156 SNPs in coding regions (124 synonymous, 26 non-synonymous, and 6 splice variants). Seven deleterious SNPs were identified in TNFSF11 , NR4A2 or ITGB4 genes. Conclusions The results from this study provide novel insights to understand the genetic architecture of internal organ traits in chickens. The QTL detection performed using a high density SNP array covered the whole genome allowing the discovery of novel QTL associated with organ traits. We identified PCGs within the QTL involved in biological processes that may regulate internal organ growth and development. Potential functional genetic variations were identified generating crucial information that, after validation, might be used in poultry breeding programs to reduce the occurrence of metabolic disorders. Electronic supplementary material The online version of this article (10.1186/s12864-019-6040-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Genome-wide association scan for QTL and their positional candidate genes associated with internal organ traits in chickens

et al. 2019

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“…3 ). Intronic SNPs can modulate gene expression, and consequently, affect the phenotype 72 , 73 . However, they are commonly deemed as potentially neutral.…”

Section: Discussionmentioning

confidence: 99%

Integration of genome wide association studies and whole genome sequencing provides novel insights into fat deposition in chicken

Moreira

Boschiero

Cesar

et al. 2018

Sci Rep

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Excessive fat deposition is a negative factor for poultry production because it reduces feed efficiency, increases the cost of meat production and is a health concern for consumers. We genotyped 497 birds from a Brazilian F2 Chicken Resource Population, using a high-density SNP array (600 K), to estimate the genomic heritability of fat deposition related traits and to identify genomic regions and positional candidate genes (PCGs) associated with these traits. Selection signature regions, haplotype blocks and SNP data from a previous whole genome sequencing study in the founders of this chicken F2 population were used to refine the list of PCGs and to identify potential causative SNPs. We obtained high genomic heritabilities (0.43–0.56) and identified 22 unique QTLs for abdominal fat and carcass fat content traits. These QTLs harbored 26 PCGs involved in biological processes such as fat cell differentiation, insulin and triglyceride levels, and lipid biosynthetic process. Three of these 26 PCGs were located within haplotype blocks there were associated with fat traits, five overlapped with selection signature regions, and 12 contained predicted deleterious variants. The identified QTLs, PCGs and potentially causative SNPs provide new insights into the genetic control of fat deposition and can lead to improved accuracy of selection to reduce excessive fat deposition in chickens.

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“…Performing such research can be a daunting undertaking because there are so many mechanisms by which variation in cis-regulatory sequences can lead to alterations in mRNA or protein expression. Sex steroid receptors in particular are extraordinarily complex, with multiple promoters, coding and noncoding exons, alternative splice variants, and isoforms (Pinsonneault et al, 2017). Below, I have reviewed the most obvious processes that can be affected by regulatory variation; those processes are also shown in Fig.…”

Section: Moving Beyond Association Studiesmentioning

confidence: 99%

Polymorphisms in sex steroid receptors: From gene sequence to behavior

Maney

2017

Frontiers in Neuroendocrinology

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Sex steroid receptors have received much interest as potential mediators of human behaviors and mental disorders. Candidate gene association studies have identified about 50 genetic variants of androgen and estrogen receptors that correlate with human behavioral phenotypes. Because most of these polymorphisms lie outside coding regions, discerning their effect on receptor function is not straightforward. Thus, although discoveries of associations improve our ability to predict risk, they have not greatly advanced our understanding of underlying mechanisms. This article is intended to serve as a starting point for psychologists and other behavioral biologists to consider potential mechanisms. Here, I review associations between polymorphisms in sex steroid receptors and human behavioral phenotypes. I then consider ways in which genetic variation can affect processes such as mRNA transcription, splicing, and stability. Finally, I suggest ways that hypotheses about mechanism can be tested, for example using in vitro assays and/or animal models.

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Intronic SNP in ESR1 encoding human estrogen receptor alpha is associated with brain ESR1 mRNA isoform expression and behavioral traits

Cited by 14 publications

References 51 publications

Genome-wide association scan for QTL and their positional candidate genes associated with internal organ traits in chickens

Genome-wide association scan for QTL and their positional candidate genes associated with internal organ traits in chickens

Integration of genome wide association studies and whole genome sequencing provides novel insights into fat deposition in chicken

Polymorphisms in sex steroid receptors: From gene sequence to behavior

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