ResearchPad - human-and-animal-genetics https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[RNA‐Seq Analysis of Genetic and Transcriptome Network Effects of Dual‐Trait Selection for Ethanol Preference and Withdrawal Using SOT and NOT Genetic Models]]> https://www.researchpad.co/article/elastic_article_7353 SOT (Old English for drunkard) mice were selected for high alcohol preference/low withdrawal, with NOTs selected for the opposite phenotype. A cluster analysis showed genetic separation of the lines with SOTs genetically closer to the C57BL/6 founder, and NOTs genetically closer to the DBA/2 founder. The effects of selection on gene expression in SOTs and NOTs implicates genes involved in cell and synaptic interactions, energy metabolism and oxidative stress in alcohol preference and withdrawal.

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<![CDATA[Novel Ethanol‐Sensitive Mutants Identified in an F3 Forward Genetic Screen]]> https://www.researchpad.co/article/N6c253323-5127-48d7-ad94-f4cb80ee1748

Background

Fetal alcohol spectrum disorders (FASD) collectively refer to all deleterious outcomes due to prenatal alcohol exposures. Alterations to the face are common phenotypes in FASD. While alcohol exposure is the underlying cause of FASD, many variables modify the outcomes of such exposures. Genetic risk is one such variable, yet we still have a limited understanding of the nature of the genetic loci mediating susceptibility to FASD.

Methods

We employed ENU‐based random mutagenesis in zebrafish to identify mutations that enhanced the teratogenicity of ethanol (EtOH). F3 embryos obtained from 126 inbred F2 families were exposed to 1% EtOH in the medium (approximately 41 mM tissue levels). Zebrafish stained with Alcian Blue and Alizarin Red were screened for qualitative alterations to the craniofacial skeleton between 4 and 7 days postfertilization (dpf).

Results

In all, we recovered 6 EtOH‐sensitive mutants, 5 from the genetic screen itself and one as a background mutation in one of our wild‐type lines. Each mutant has a unique EtOH‐induced phenotype relative to the other mutant lines. All but 1 mutation appears to be recessive in nature, and only 1 mutant, au29, has apparent craniofacial defects in the absence of EtOH. To validate the genetic screen, we genetically mapped au29 and found that it carries a mutation in a previously uncharacterized gene, si:dkey‐88l16.3.

Conclusions

The phenotypes of these EtOH‐sensitive mutants differ from those in previous characterizations of gene–EtOH interactions. Thus, each mutant is likely to provide novel insights into EtOH teratogenesis. Given that most of these mutants only have craniofacial defects in the presence of EtOH and our mapping of au29, it is also likely that many of the mutants will be previously uncharacterized. Collectively, our findings point to the importance of unbiased genetic screens in the identification, and eventual characterization, of risk alleles for FASD.

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<![CDATA[Association of the CHRNA4 Neuronal Nicotinic Receptor Subunit Gene with Frequency of Binge Drinking in Young Adults]]> https://www.researchpad.co/article/5ba6aed240307c29fb0f9a6a

Background

Binge drinking is responsible for over half of all alcohol‐related deaths and results in significant health and economic costs to individuals and society. Knowledge of genetic aspects of this behavior, particularly as it emerges in young adulthood, could lead to improved treatment and prevention programs.

Methods

We have focused on the association of variation in neuronal nicotinic receptor subunit genes (CHRNs) in a cohort of 702 Hispanic and non‐Hispanic White young adults who are part of the Social and Emotional Contexts of Adolescent Smoking Patterns (SECASP) study. Fifty‐five single nucleotide polymorphisms (SNPs) covering the variation in 5 CHRNs (CHRNA4,CHRNB2,CHRNA2, CHRNB3A6, and CHRNA5A3B4) were studied.

Results

Frequency of binge drinking and other correlated alcohol consumption measures were significantly associated with SNPs in CHRNA4 (p‐values ranged from 0.0003 to 0.02), but not with SNPs in other CHRNs. This association was independent of smoking status in our cohort.

Conclusions

Variants in CHRNA4 may contribute to risk of binge drinking in young adults in this cohort. Results will need to be confirmed in independent samples.

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