最近一項新的研究發(fā)現(xiàn),，男性精神疾病的嚴(yán)重程度不同與GDI1基因的拷貝數(shù)有關(guān),，該基因位于X-染色體上，GDI1基因的拷貝數(shù)越多,，疾病也越嚴(yán)重,。這項研究發(fā)表在最近一期的American Journal of Human Genetics雜志上。
科學(xué)家研究了患有相關(guān)疾病的好幾個家族,，通過研究首次發(fā)現(xiàn)精神病的嚴(yán)重程度與X染色體上GDI1基因的拷貝數(shù)有關(guān),。攜帶5個拷貝的GDI1基因一般比攜帶2個拷貝GDI1基因的智力低下程度更嚴(yán)重。
之前有研究人員發(fā)現(xiàn)一些X連鎖的智力低下患者GDI1基因缺失,。這些患者大腦內(nèi)GDI1產(chǎn)生的途徑被中斷,，導(dǎo)致各種刺激無法傳遞到大腦皮層。這項新的研究表明,，過量產(chǎn)生GDI1對人的智力也同樣有危害,。
弱智在總?cè)丝谥械陌l(fā)病比例為2--3%。造成這一缺陷有外部因素,，如分娩時胎兒缺氧等,；也有可能由于遺傳因素決定。因此,，準(zhǔn)確找出導(dǎo)致缺陷的原因?qū)⒂兄跒榛颊咛峁└玫闹委煼椒?。（生物谷Bioon.com）
人類智力研究：
BMC Neuroscience：用磁脈沖刺激大腦有助提高智力
PNAS：嬰兒智商高低與母乳喂養(yǎng)無關(guān) 某種酶成關(guān)鍵因素
Am J Hum Genet.：MECP2的表達(dá)與男性的智力障礙直接相關(guān)
PNAS：噪音影響嬰幼兒聽力和智力發(fā)育
生物谷推薦原始出處：
The American Journal of Human Genetics, Volume 85, Issue 6, 809-822, 11 December 2009
Dosage-Dependent Severity of the Phenotype in Patients with Mental Retardation Due to a Recurrent Copy-Number Gain at Xq28 Mediated by an Unusual Recombination
Joke Vandewalle1, 2, 9, Hilde Van Esch3, 9, Karen Govaerts1, 2, Jelle Verbeeck1, 2, Christiane Zweier4, Irene Madrigal5, Montserrat Mila5, Elly Pijkels3, Isabel Fernandez6, Jürgen Kohlhase7, Christiane Spaich8, Anita Rauch4, Jean-Pierre Fryns3, Peter Marynen1, 2 and Guy Froyen1, 2, ,
1 Human Genome Laboratory, Department for Molecular and Developmental Genetics, VIB, B-3000 Leuven, Belgium
2 Human Genome Laboratory, Center for Human Genetics, K.U. Leuven, B-3000 Leuven, Belgium
3 Center for Human Genetics, University Hospital Leuven, K.U. Leuven, B-3000 Leuven, Belgium
4 Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, D-91054 Erlangen, Germany
5 Biochemistry and Molecular Genetics Department Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer and CIBERER, 08036 Barcelona, Spain
6 Instituto de Biología y Genética Molecular, Universidad de Valladolid, 47003 Valladolid, Spain
7 Center for Human Genetics Freiburg, D-79106 Freiburg, Germany
8 Institute for Clinical Genetics, Olgahospital, D-70176 Stuttgart, Germany
We report on the identification of a 0.3 Mb inherited recurrent but variable copy-number gain at Xq28 in affected males of four unrelated families with X-linked mental retardation (MR). All aberrations segregate with the disease in the families, and the carrier mothers show nonrandom X chromosome inactivation. Tiling Xq28-region-specific oligo array revealed that all aberrations start at the beginning of the low copy repeat LCR-K1, at position 153.20 Mb, and end just distal to LCR-L2, at 153.54 Mb. The copy-number gain always includes 18 annotated genes, of which RPL10, ATP6AP1 and GDI1 are highly expressed in brain. From these, GDI1 is the most likely candidate gene. Its copy number correlates with the severity of clinical features, because it is duplicated in one family with nonsyndromic moderate MR, is triplicated in males from two families with mild MR and additional features, and is present in five copies in a fourth family with a severe syndromic form of MR. Moreover, expression analysis revealed copy-number-dependent increased mRNA levels in affected patients compared to control individuals. Interestingly, analysis of the breakpoint regions suggests a recombination mechanism that involves two adjacent but different sets of low copy repeats. Taken together, our data strongly suggest that an increased expression of GDI1 results in impaired cognition in a dosage-dependent manner. Moreover, these data also imply that a copy-number gain of an individual gene present in the larger genomic aberration that leads to the severe MECP2 duplication syndrome can of itself result in a clinical phenotype as well.
