Systems genetic analysis of binge-like eating in a C57BL/6J x DBA/2J-F2 cross,Genes, Brain and Behavior

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Systems genetic analysis of binge-like eating in a C57BL/6J x DBA/2J-F2 cross
Genes, Brain and Behavior ( IF 2.4 ) Pub Date : 2021-05-12 , DOI: 10.1111/gbb.12751
Emily J Yao ₁ , Richard K Babbs ₁ , Julia C Kelliher ₁ , Kimberly P Luttik ₁ , Kristyn N Borrelli _{1,

2,

3,

4} , M Imad Damaj ₅ , Megan K Mulligan ₆ , Camron D Bryant _{1,

2,

3,

4}

Affiliation

Binge eating is a heritable trait associated with eating disorders and refers to the rapid consumption of a large quantity of energy-dense food that is, associated with loss of control and negative affect. Binge eating disorder is the most common eating disorder in the United States; however, the genetic basis is unknown. We previously identified robust mouse inbred strain differences between C57BL/6J and DBA/2J in binge-like eating of sweetened palatable food in an intermittent access, conditioned place preference paradigm. To map the genetic basis of changes in body weight and binge-like eating (BLE) and to identify candidate genes, we conducted quantitative trait locus (QTL) analysis in 128 C57BL/6J x DBA/2J-F2 mice combined with PheQTL and trait covariance analysis in GeneNetwork2 using legacy BXD-RI trait datasets. We identified a QTL on Chromosome 18 influencing changes in body weight across days in females (log of the odds [LOD] = 6.3; 1.5-LOD: 3–12 cM) that contains the candidate gene Zeb1. We also identified a sex-combined QTL influencing initial palatable food intake on Chromosome 5 (LOD = 5.8; 1.5-LOD: 21–28 cM) that contains the candidate gene Lcorl and a second QTL influencing escalated palatable food intake on Chromosome 6 in males (LOD = 5.4; 1.5-LOD: 50–59 cM) that contains the candidate genes Adipor2 and Plxnd1. Finally, we identified a suggestive QTL in females for slope of BLE on distal Chromosome 18 (LOD = 4.1; p = 0.055; 1.5-LOD: 23–35 cM). Future studies will use BXD-RI strains to fine map loci and support candidate gene nomination for gene editing.

中文翻译：

C57BL/6J x DBA/2J-F2 杂交中暴饮暴食的系统遗传分析

暴饮暴食是一种与饮食失调相关的遗传特征，是指快速消耗大量能量密集的食物，即与失控和负面情绪相关。暴食症是美国最常见的饮食失调症。然而，遗传基础尚不清楚。我们之前发现了 C57BL/6J 和 DBA/2J 之间在间歇性获取、条件性位置偏好范式中暴饮暴食甜味可口食物方面的小鼠近交系之间的显着差异。为了绘制体重和暴饮暴食 (BLE) 变化的遗传基础并确定候选基因，我们对 128 只 C57BL/6J x DBA/2J-F2 小鼠结合 PheQTL 和性状进行了数量性状位点 (QTL) 分析。使用旧版 BXD-RI 性状数据集在 GeneNetwork2 中进行协方差分析。我们在 18 号染色体上发现了一个 QTL，该 QTL 影响女性体重的几天变化（对数 [LOD] = 6.3；1.5-LOD：3-12 cM），其中包含候选基因Zeb1 。我们还确定了一个影响 5 号染色体上初始可口食物摄入量的性别组合 QTL（LOD = 5.8；1.5-LOD：21-28 cM），其中包含候选基因Lcorl和一个影响雄性 6 号染色体上可口食物摄入量逐步增加的第二个 QTL （LOD = 5.4；1.5-LOD：50-59 cM），包含候选基因Adipor2和Plxnd1 。最后，我们在雌性中确定了远端 18 号染色体上 BLE 斜率的提示性 QTL（LOD = 4.1； p = 0.055；1.5-LOD：23-35 cM）。未来的研究将使用 BXD-RI 菌株来精细定位基因座并支持基因编辑的候选基因提名。

更新日期：2021-07-07

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