Dashti Mohammed, Alsaleh Hussain, Eaaswarkhanth Muthukrishnan, John Sumi Elsa, Nizam Rasheeba, Melhem Motasem, Hebbar Prashantha, Sharma Prem, Al-Mulla Fahd, Thanaraj Thangavel Alphonse
Genetics and Bioinformatics Department, Dasman Diabetes Institute, Kuwait City, Kuwait.
Kuwait Identification DNA Laboratory, General Department of Criminal Evidence, Ministry of Interior, Kuwait City, Kuwait.
Front Genet. 2021 Feb 11;12:626260. doi: 10.3389/fgene.2021.626260. eCollection 2021.
BACKGROUND/OBJECTIVES: Whole-exome sequencing is a valuable tool to determine genetic variations that are associated with rare and common health conditions. A limited number of studies demonstrated that mitochondrial DNA can be captured using whole-exome sequencing. Previous studies have suggested that mitochondrial DNA variants and haplogroup lineages are associated with obesity. Therefore, we investigated the role of mitochondrial variants and haplogroups contributing to the risk of obesity in Arabs in Kuwait using exome sequencing data.
SUBJECTS/METHODS: Indirect mitochondrial genomes were extracted from exome sequencing data from 288 unrelated native Arab individuals from Kuwait. The cohort was divided into obese [body mass index (BMI) ≥ 30 kg/m] and non-obese (BMI < 30 kg/m) groups. Mitochondrial variants were identified, and haplogroups were classified and compared with other sequencing technologies. Statistical analysis was performed to determine associations and identify mitochondrial variants and haplogroups affecting obesity.
Haplogroup R showed a protective effect on obesity [odds ratio (OR) = 0.311; = 0.006], whereas haplogroup L individuals were at high risk of obesity (OR = 2.285; = 0.046). Significant differences in mitochondrial variants between the obese and non-obese groups were mainly haplogroup-defining mutations and were involved in processes in energy generation. The majority of mitochondrial variants and haplogroups extracted from exome were in agreement with technical replica from Sanger and whole-genome sequencing.
This is the first to utilize whole-exome data to extract entire mitochondrial haplogroups to study its association with obesity in an Arab population.
背景/目的：全外显子组测序是确定与罕见和常见健康状况相关的基因变异的重要工具。少数研究表明，全外显子组测序可用于捕获线粒体DNA。此前的研究表明，线粒体DNA变异和单倍群谱系与肥胖有关。因此，我们利用外显子组测序数据，研究线粒体变异和单倍群在科威特阿拉伯人群肥胖风险中的作用。
对象/方法：从288名来自科威特的无亲缘关系的阿拉伯本地个体的外显子组测序数据中提取间接线粒体基因组。该队列分为肥胖组[体重指数（BMI）≥30kg/m²]和非肥胖组（BMI<30kg/m²）。鉴定线粒体变异，对单倍群进行分类，并与其他测序技术进行比较。进行统计分析以确定关联，并识别影响肥胖的线粒体变异和单倍群。
单倍群R对肥胖具有保护作用[比值比（OR）=0.311；P=0.006]，而单倍群L个体肥胖风险较高（OR=2.285；P=0.046）。肥胖组和非肥胖组之间线粒体变异的显著差异主要是单倍群定义突变，且参与能量生成过程。从外显子组中提取的大多数线粒体变异和单倍群与桑格测序和全基因组测序的技术复制品一致。
这是首次利用全外显子组数据提取完整的线粒体单倍群，以研究其与阿拉伯人群肥胖的关联。
