与肥胖有关的基因特征近来多有报道，但让人超瘦的基因特征很少被发现和提起。英国《自然》杂志网站刊登的一项最新研究结果认为，有些基因的数量如果太多，就有可能让人骨瘦如柴。
由英国、瑞士、法国等多国研究人员共同完成的这份研究报告说，研究人员调查了超过9．5万人的基因数据，结果发现，如果第16号染色体上名为16p11．2的一个区域中的基因被过多复制，就会让人超瘦。如果拥有过多的相关基因，男性超瘦的风险会是正常人的23倍，而女性超瘦的风险也会是正常人的5倍。这里超瘦的定义是体重指数低于18．5，已属于不健康的瘦的范畴。
通常人体内每个基因只有两份，但实际上不完全如此，一个人的基因组有些地方可能会丢失一些基因，而另一些地方又会出现过多的某些基因。这种基因的丢失和冗余许多时候没有什么影响，但有时也会带来疾病。
比如本次研究关注的名为16p11．2的区域中的基因，以前曾发现如果这些基因丢失，那么肥胖症的风险就会大大增加。丢失这些基因的人变得肥胖的风险是正常人的43倍。参与研究的英国帝国理工学院教授菲利普·弗罗盖尔指出，这还是首次发现同一批基因的丢失和冗余会造成相反的影响。
据介绍，在这个区域中共有28个基因，研究人员计划对它们进行详细分析，找出它们影响胖瘦的深层原因。(生物谷 Bioon.com）
doi:10.1038/nature10406
PMC:
PMID:
Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus
Sébastien Jacquemont,Alexandre Reymond，Flore Zufferey，Robin G. Walters,Louise Harewood,et al.
Both obesity and being underweight have been associated with increased mortality1, 2. Underweight, defined as a body mass index (BMI) ≤18.5kgper m2 in adults and ≤standard deviations from the mean in children, is the main sign of a series of heterogeneous clinical conditions including failure to thrive, feeding and eating disorder and/or anorexia nervosa. In contrast to obesity, few genetic variants underlying these clinical conditions have been reported. We previously showed that hemizygosity of a ~600-kilobase (kb) region on the short arm of chromosome 16 causes a highly penetrant form of obesity that is often associated with hyperphagia and intellectual disabilities. Here we show that the corresponding reciprocal duplication is associated with being underweight. We identified 138 duplication carriers (including 132 novel cases and 108 unrelated carriers) from individuals clinically referred for developmental or intellectual disabilities (DD/ID) or psychiatric disorders, or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight and BMI. Half of the boys younger than five years are underweight with a probable diagnosis of failure to thrive, whereas adult duplication carriers have an 8.3-fold increased risk of being clinically underweight. We observe a trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive eating behaviours and a significant reduction in head circumference. Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus. The phenotypes correlate with changes in transcript levels for genes mapping within the duplication but not in flanking regions. The reciprocal impact of these 16p11.2 copy-number variants indicates that severe obesity and being underweight could have mirror aetiologies, possibly through contrasting effects on energy balance.
