Effect of Trinucleotide Repeats in the Huntington's Gene on Intelligence.
Effect of Trinucleotide Repeats in the Huntington's Gene on Intelligence.
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DOI：
10.1016/j.ebiom.2018.03.031
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发表时间：
2018-05
期刊：
影响因子：
11.1
通讯作者：
Nopoulos P
中科院分区：
文献类型：
--
作者：
Lee JK;Conrad A;Epping E;Mathews K;Magnotta V;Dawson JD;Nopoulos P
亨廷顿氏病（HD）是由HTT基因异常引起的。该基因包括范围从10到35的三核苷酸重复，并且当扩展超过39时，导致HD。我们以前报道过CAG重复在正常范围内对大脑发育有直接和有益的影响，更高的重复与更高的认知功能相关。目前的研究扩展了这一调查范围，以评估CAG重复在整个重复范围（从15到58）中的影响。我们评估了6-18岁儿童的大脑功能。处理DNA样品以定量HTT内CAG重复的数目。使用线性回归来确定CAG重复的数量是否预测脑功能的测量。HTT中的重复次数对一般智力的测量具有倒U形模式的非线性影响。增加重复长度与更高的GAI评分相关，直到大约40-41次重复。在这个峰值之后，增加重复长度与GAI分数下降相关。HTT可能会带来优势或劣势，这取决于重复序列的长度，在智力的确定中发挥关键作用，或导致独特的人类大脑疾病。HTT基因在正常人群中包括范围为10至35的三核苷酸重复。亨廷顿氏病是由HTT基因中的三核苷酸重复扩增超出正常范围引起的。该基因对大脑发育至关重要，其中每个重复都有助于大脑功能的发展，以智力衡量。增加重复在一定程度上是有益的，然后对智力不利，形成倒U型关系。浮士德式的交易：人类大脑进化的关键能在一种可怕的疾病中找到吗？亨廷顿氏病是一种由单一基因引起的致命的进行性脑部疾病。目前的研究结果表明，相同的基因对大脑发育和智力都很重要。因此，这种基因可能同时具有优势和劣势：在进化出上级人脑中发挥作用，但同时也是人类特有的脑部疾病的劣势。
Huntington's Disease (HD) is caused by an abnormality in the HTT gene. This gene includes trinucleotide repeats ranging from 10 to 35, and when expanded beyond 39, causes HD. We previously reported that CAG repeats in the normal range had a direct and beneficial effect on brain development with higher repeats being associated with higher cognitive function. The current study now expands this line of inquiry to evaluate the effects of CAG repeat throughout the entire spectrum of repeats from 15 to 58. We evaluated brain function in children ages 6–18 years old. DNA samples were processed to quantify the number of CAG repeats within HTT. Linear regression was used to determine if number of CAG repeats predicted measures of brain function. The number of repeats in HTT, had a non-linear effect on a measure of general intelligence with an inverted U shape pattern. Increasing repeat length was associated with higher GAI scores up until roughly 40–41 repeats. After this peak, increasing repeat length was associated with declining GAI scores. HTT may confer an advantage or a disadvantage depending upon the repeat length, playing a key role in the determination of intelligence, or causing a uniquely human brain disease. The HTT gene includes trinucleotide repeats ranging from 10 to 35 in the normal population. Huntington’s disease is caused when the trinucleotide repeats in the HTT gene expand beyond the normal range. The gene is vital for brain growth in which each repeat contributes to the development of brain function, measured as intelligence. Increasing repeats are beneficial to a certain point, then becomes detrimental to intelligence, forming an inverted U relationship. A Faustian Bargain: Could the key to the evolution of the human brain be found in a dreadful disease? Huntington's Disease is a fatal progressive brain disease caused by a single gene. Results from the current study show that the same gene is important for brain development and intelligence. Therefore, this gene may have a simultaneous advantage and disadvantage: a role in the evolution of a superior human brain, yet the disadvantage of a uniquely human brain disease.
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影响因子：
6.1
作者：
Arteaga-Bracho, Eduardo E.;Gulinello, Maria;Winchester, Michael L.;Pichamoorthy, Nandini;Petronglo, Jenna R.;Zambrano, Alicia D.;Inocencio, Julio;De Jesus, Chirstopher D.;Louie, Joseph O.;Gokhan, Solen;Mehler, Mark F.;Molero, Aldrin E.
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Molero, Aldrin E.
影响因子：
15.9
作者：
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通讯作者：
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影响因子：
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作者：
Nopoulos, Peg;Epping, Eric A.;Perlmutter, Joel
通讯作者：
Perlmutter, Joel
影响因子：
11
作者：
Plomin, R.;Deary, I. J.
通讯作者：
Deary, I. J.
影响因子：
3
作者：
Deary, IJ;Whalley, LJ;Starr, JM
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