與肥胖有關(guān)的基因特征近來多有報(bào)道，但讓人超瘦的基因特征很少被發(fā)現(xiàn)和提起,。英國(guó)《自然》雜志網(wǎng)站刊登的一項(xiàng)最新研究結(jié)果認(rèn)為,，有些基因的數(shù)量如果太多，就有可能讓人骨瘦如柴,。
由英國(guó),、瑞士、法國(guó)等多國(guó)研究人員共同完成的這份研究報(bào)告說,，研究人員調(diào)查了超過9．5萬人的基因數(shù)據(jù),，結(jié)果發(fā)現(xiàn)，如果第16號(hào)染色體上名為16p11．2的一個(gè)區(qū)域中的基因被過多復(fù)制,，就會(huì)讓人超瘦,。如果擁有過多的相關(guān)基因，男性超瘦的風(fēng)險(xiǎn)會(huì)是正常人的23倍,，而女性超瘦的風(fēng)險(xiǎn)也會(huì)是正常人的5倍,。這里超瘦的定義是體重指數(shù)低于18．5，已屬于不健康的瘦的范疇,。
通常人體內(nèi)每個(gè)基因只有兩份,，但實(shí)際上不完全如此，一個(gè)人的基因組有些地方可能會(huì)丟失一些基因,，而另一些地方又會(huì)出現(xiàn)過多的某些基因,。這種基因的丟失和冗余許多時(shí)候沒有什么影響，但有時(shí)也會(huì)帶來疾病,。
比如本次研究關(guān)注的名為16p11．2的區(qū)域中的基因,，以前曾發(fā)現(xiàn)如果這些基因丟失，那么肥胖癥的風(fēng)險(xiǎn)就會(huì)大大增加,。丟失這些基因的人變得肥胖的風(fēng)險(xiǎn)是正常人的43倍,。參與研究的英國(guó)帝國(guó)理工學(xué)院教授菲利普·弗羅蓋爾指出，這還是首次發(fā)現(xiàn)同一批基因的丟失和冗余會(huì)造成相反的影響,。
據(jù)介紹,，在這個(gè)區(qū)域中共有28個(gè)基因，研究人員計(jì)劃對(duì)它們進(jìn)行詳細(xì)分析,，找出它們影響胖瘦的深層原因,。(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，F(xiàn)lore 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.
