生物谷報(bào)道：在新一期的BMC Genetics雜志的網(wǎng)絡(luò)版上,，來(lái)自Monell中心的研究人員首次嘗試估算出控制肥胖和體重的基因數(shù)量。他們的研究發(fā)現(xiàn)有超過(guò)6000個(gè)基因（大約占基因組的25％）幫助確定一個(gè)人的體重,。
研究人員表示,，他們的研究結(jié)果暗示出，之前一些研究發(fā)現(xiàn)的每個(gè)與體重有關(guān)的基因只是數(shù)千個(gè)影響體重的基因中的一個(gè)而已,，因此快速地解決體重問(wèn)題是不可能的,。
為了能夠估計(jì)出影響體重的基因數(shù)量，Monell的研究人員研究了Jackson實(shí)驗(yàn)室小鼠基因組數(shù)據(jù)庫(kù),，尋找與敲除小鼠的體重有關(guān)的信息。
每個(gè)敲除小鼠都有一個(gè)特定的基因被失活,。通過(guò)研究這些敲除小鼠與正常小鼠的差異,，研究人員能夠獲得基因功能以及是否導(dǎo)致疾病發(fā)生的信息。小鼠能夠提供有關(guān)人類疾病的有用信息,，這是因?yàn)樗鼈兙哂信c人類相同的很多基因,。
這種敲除方法非常有用，2007年諾貝爾生理醫(yī)學(xué)獎(jiǎng)就頒發(fā)給了這項(xiàng)技術(shù)的發(fā)明者,。敲除小鼠目前是所有行為和疾病小鼠模型的標(biāo)準(zhǔn)研究工具,。
在60％的小鼠株中，敲除一個(gè)基因會(huì)導(dǎo)致小鼠無(wú)法存活,。Monell的研究發(fā)現(xiàn),，體重情況在超過(guò)三分之一的可存活敲除小鼠中發(fā)生了改變,；31％使體重比對(duì)照輕，而另外3％則使體重增加了,。
根據(jù)小鼠基因組中的基因數(shù)量進(jìn)行推算,，這意味著有超過(guò)6000個(gè)基因可能影響小鼠的體重,。
研究人員評(píng)論說(shuō),，這項(xiàng)研究的研究很尤其,，它揭示出促進(jìn)體重增加的基因數(shù)量是使體重減少的基因數(shù)量的10倍——這也可能解釋了為什么增加體重比減肥更容易,。
因?yàn)轶w重是許多疾病的一個(gè)影響因子，包括高血壓,、糖尿病和心臟病,。這些新發(fā)現(xiàn)的意義在于超越了之前的肥胖和體重研究。影響這些疾病和其他疾病的基因敲除信息的公布將有可能對(duì)減少體重產(chǎn)生廣泛影響,。
這些發(fā)現(xiàn)還具有臨床意義,。醫(yī)生和其他關(guān)心個(gè)性化醫(yī)療發(fā)展的專業(yè)人員需要拓寬他們的遺傳學(xué)思路,，要意識(shí)到許多基因一起作用才能決定疾病的敏感性。
生物谷推薦原始出處：
BMC Genetics
Reduced body weight is a common effect of gene knockout in mice
Danielle R Reed , Maureen P Lawler and Michael G Tordoff
BMC Genetics 2008, 9:4doi:10.1186/1471-2156-9-4
Published: 8 January 2008
Background
During a search for obesity candidate genes in a small region of the mouse genome, we noticed that many genes when knocked out influenced body weight. To determine whether this was a general feature of gene knockout or a chance occurrence, we surveyed the Jackson Laboratory Mouse Genome Database for knockout mouse strains and their phenotypes. Body weights were not available for all strains so we also obtained body weight information by contacting a random sample of investigators responsible for a knockout strain.
Results
We classified each knockout mouse strain as (1) lighter and smaller, (2) larger and heavier, or (3) the same weight, relative to control mice. We excluded knockout strains that died early in life, even though this type of lethality is often associated with a small embryo or reduced body size. Based on a dataset of 1,977 knockout strains, we found that 31% of viable knockout mouse strains weighed less and an additional 3% weighed more than did controls.
Conclusions
Body weight is potentially a latent variable in about a third of experiments that use knockout mice and should be considered in interpreting experimental outcomes, e.g., in studies of hypertension, drug and hormone metabolism, organ development, cell proliferation and apoptosis, digestion, heart rate, or atherosclerosis. If we assume that the knockout genes we surveyed are representative then upward of 6,000 genes are predicted to influence the size of a mouse. Body weight is highly heritable, and numerous quantitative trait loci have been mapped in mice, but 'multigenic' is an insufficient term for the thousands of loci that could contribute to this complex trait.
