Genetic Basis of Aerobically Supported Voluntary Exercise: Results from a Selection Experiment with House Mice
GENETICS
Authors: Hillis, David A.; Yadgary, Liran; Weinstock, George M.; Pardo-Manuel de Villena, Fernando; Pomp, Daniel; Fowler, Alexandra S.; Xu, Shizhong; Chan, Frank; Garland, Theodore, Jr.
Abstract
House mice from 4 replicate lines selectively bred for 61 generations for voluntary wheel-running behavior were compared with 4 non-selected control lines using multiple genome-wide analytical techniques on both haplotype and single nucleotide polymorphism data...... The biological basis of exercise behavior is increasingly relevant for maintaining healthy lifestyles. Various quantitative genetic studies and selection experiments have conclusively demonstrated substantial heritability for exercise behavior in both humans and laboratory rodents. In the "High Runner" selection experiment, four replicate lines of Mus domesticus were bred for high voluntary wheel running (HR), along with four nonselected control (C) lines. After 61 generations, the genomes of 79 mice (9-10 from each line) were fully sequenced and single nucleotide polymorphisms (SNPs) were identified. We used nested ANOVA with MIVQUE estimation and other approaches to compare allele frequencies between the HR and C lines for both SNPs and haplotypes. Approximately 61 genomic regions, across all somatic chromosomes, showed evidence of differentiation; 12 of these regions were differentiated by all methods of analysis. Gene function was inferred largely using Panther gene ontology terms and KO phenotypes associated with genes of interest. Some of the differentiated genes are known to be associated with behavior/motivational systems and/or athletic ability, including Sorl1, Dach1, and Cdh10. Sorl1 is a sorting protein associated with cholinergic neuron morphology, vascular wound healing, and metabolism. Dach1 is associated with limb bud development and neural differentiation. Cdh10 is a calcium ion binding protein associated with phrenic neurons. Overall, these results indicate that selective breeding for high voluntary exercise has resulted in changes in allele frequencies for multiple genes associated with both motivation and ability for endurance exercise, providing candidate genes that may explain phenotypic changes observed in previous studies.
Association between the SORL1 rs2070045 polymorphism and late-onset Alzheimer's disease: Interaction with the ApoE genotype in the Chinese Han population
NEUROSCIENCE LETTERS
Authors: Xue, Xiaofan; Zhang, Milan; Lin, Yicong; Xu, Erhe; Jia, Jianping
Abstract
Late-onset Alzheimer's Disease (LOAD) is a common neurodegenerative disease [1], and the two well identified pathological hallmarks of LOAD are senile plaques formed from amyloid [3 peptides (A13) and neurofibrillary tangles (NFTs) consisting of hyperphorylated tau protein [2]. The neuronal Sortilin-related receptor (SORL1) is involved in the processing and trafficking of amyloid precursor protein (APP) into recycling pathways, thus influencing Ap generation and by this AD pathology [3]. To explore the relationship between the single nucleotide polymorphism (SNP) of the SORL1 SNP 19 rs2070045 and LOAD, a case-control study was conducted in a Chinese Han cohort including 77 LOAD patients and 100 control participants. This SNP 19 rs2070045 was genotyped with a polymerase chain reaction-restriction fragment length polymorphism, (PCR-RFLP) method. The association was revealed between the polymorphism of SNP 19 rs2070045 (T/T, T/G, GIG) and the risk of LOAD. The results of this study indicated that the T allele (T/G+T/T) of SNP 19 rs2070045 was successful in exerting obvious influence in LOAD patients (x2= 4.884, P= 0.027 < 0.05). However, there is no sufficient evidence to prove that the T allele of SNP 19 rs2070045 is associated with s4 allele of ApoE gene in LOAD patients (x2 = 0.771, P= 0.380 > 0.05). (C) 2013 Elsevier Ireland Ltd. All rights reserved.