生物谷報道：一項新研究顯示,，自閉癥障礙癥候群患者比正常人更可能有某些DNA序列的額外拷貝,。這項研究結果被發(fā)表在3月15日的《科學》雜志在線版上,。
這些被稱為“拷貝數(shù)變異”的突變在不同的患者身上影響不同的基因,，意味著自閉癥行為能來自許多不同的遺傳缺陷,?？截悢?shù)變異主要影響偶發(fā)病例,，也就是兄弟姐妹中只有一人患自閉癥的情況,，而在家庭病例（多個兄弟姐妹患病）中不太重要,。雖然雙胞胎研究曾揭示自閉癥具有高度遺傳性,，但是大多數(shù)病例沒有家族自閉癥史。研究遺傳模式的連鎖和關聯(lián)分析未能找到強的候選基因,，意味著自閉癥的遺傳風險是一個相當復雜的問題,。Jonathan Sebat和同事分析了264個家庭中的拷貝數(shù)變異，包括118個有一個自閉癥患者的“單純性”家庭、47個有多個患者的“多發(fā)性”家庭,、以及99個沒有自閉癥診斷的對照家庭,。他們在10%的單純性家庭、2%的多發(fā)性家庭,、以及1%的對照家庭中發(fā)現(xiàn)拷貝數(shù)變異,。文章作者指出，這些變異看來在自閉癥中起主要作用,，但是不知道變異是如何起作用的,。
原文出處：
Strong Association of De Novo Copy Number Mutations with Autism
Jonathan Sebat, B. Lakshmi, Dheeraj Malhotra, Jennifer Troge, Christa Lese-Martin, Tom Walsh, Boris Yamrom, Boris Yamrom, Seungtai Yoon, Alex Krasnitz, Jude Kendall, Anthony Leotta, Deepa Pai, Ray Zhang, Yoon-Ha Lee, James Hicks, Sarah J. Spence, Annette T. Lee, Kaija Puura, Terho Lehtimäki, David Ledbetter, Peter K. Gregersen, Joel Bregman, James S. Sutcliffe, Vaidehi Jobanputra, Wendy Chung, Dorothy Warburton, Mary-Claire King, David Skuse, Daniel H. Geschwind, T. Conrad Gilliam, Kenny Ye, and Michael Wigler
Published online 15 March 2007 [DOI: 10.1126/science.1138659] (in Science Express Reports)
Abstract » PDF » Supporting Online Material »
作者簡介：
Jonathan Sebat
Assistant Professor
Ph.D. University of Idaho, 2002
Copy number variation; segmental duplication; genetics; neurogenetics; ROMA; microarray
Large-scale differences in gene copy number, known as copy number polymorphisms (CNPs), are a significant source of human genetic variation. In contrast to DNA sequence variants such as SNPs and microsatellite repeats, CNPs have not been well characterized. Much remains to be learned about the genomic locations, frequency, and stability of these structural variants and their importance in human genetic disease.
Our laboratory is interested in the role of gene copy number variation in neurological disease. Almost invariably, visible alterations of the genome result in cognitive defects. In addition, some neurological disorders are the result of heritable chromosomal variants invisible at the cytogenetic level. We hypothesize that submicroscopic alterations in gene dosage are underlying causes of diseases such as autism, schizophrenia, and Parkinson’s disease. We are currently investigating chromosomal variation in disease using a method for high-resolution analysis of DNA copy number called Representational Oligonucleotide Microarray Analysis (ROMA).
We have previously applied ROMA to the analysis of cytogenetic aberrations. This analysis has served to validate the method and to illustrate the resolution with which we can define chromosomal imbalances. In addition, through our studies of “normal” genetic variation, we have shown that CNPs are abundant and widely distributed in the human genome. We have now adapted ROMA for use in population studies of genomic variation. Our flagship project is an exploration of copy number variation in familial and sporadic autism.
Selected Publications
Jobanputra,V., J. Sebat, W. Chung, K. Anyane-Yeboa, M. Wigler, and D. Warburton. 2005. Application of ROMA (representational oligonucleotide microarray analysis) to patients with cytogenetic rearrangements. Genet. Med. 7: 111-118.
Sebat, J., L. Muthuswamy, J.,Troge, J. Alexander, J. Young, P. Lundin, S. Maner, H. Massa, M. Walker, M. Chi, N. Navin, R. Lucito, J. Healy, A. Reiner, J. Hicks, K. Ye, A. Reiner, T.C. Gilliam, B. Trask, N. Patterson, A. Zetterberg, and M. Wigler. 2004. Large-Scale Copy Number Polymorphism in the Human Genome. Science 305: 525-528.
Lucito, R., J. Healy, J. Alexander, A. Reiner, D. Esposito, M. Chi, L. Rodgers, A. Brady, J. Sebat, J. Troge, J.A. West, S. Rostan, K.C. Nguyen, S. Powers K.Q. Ye, A. Olshen, E. Venkatraman, L. Norton, and M. Wigler. 2003. Representational oligonucleotide microarray analysis: a high-resolution method to detect genome copy number variation. Genome Res. 13: 2291-2305.
