Identifying autism loci and genes by tracing recent shared ancestry

被引：524

作者：

Morrow, Eric M. ^{[1
,2
,3
,4
,5
,6
,7
,8
]}

Yoo, Seung-Yun ^{[1
,2
,3
,4
,6
,7
,8
]}

Flavell, Steven W. ^{[8
,9
,10
,11
]}

Kim, Tae-Kyung ^{[8
,9
,10
,11
]}

Lin, Yingxi ^{[8
,9
,10
,11
]}

Hill, Robert Sean ^{[1
,2
,3
,4
,6
,7
,8
]}

Mukaddes, Nahit M. ^{[12
]}

Balkhy, Soher ^{[13
]}

Gascon, Generoso ^{[13
,14
]}

Hashmi, Asif ^{[15
]}

Al-Saad, Samira ^{[16
]}

Ware, Janice ^{[8
,17
]}

Joseph, Robert M. ^{[8
,18
]}

Greenblatt, Rachel ^{[1
,2
,3
,4
]}

Gleason, Danielle ^{[1
,2
,3
,4
]}

Ertelt, Julia A. ^{[1
,2
,3
,4
]}

Apse, Kira A. ^{[1
,2
,3
,4
,8
]}

Bodell, Adria ^{[1
,2
,3
,4
]}

Partlow, Jennifer N. ^{[1
,2
,3
,4
]}

Barry, Brenda ^{[1
,2
,3
,4
]}

Yao, Hui ^{[1
,2
]}

Markianos, Kyriacos ^{[1
,2
]}

Ferland, Russell J. ^{[19
]}

Greenberg, Michael E. ^{[8
,9
,10
,11
]}

Walsh, Christopher A. ^{[1
,2
,3
,4
,6
,7
,8
]}

机构：

[1] Childrens Hosp, Div Genet, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Boston, MA 02115 USA

[3] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA

[4] Beth Israel Deaconess Med Ctr, Howard Hughes Med Inst, Boston, MA 02115 USA

[5] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA

[6] MIT, Program Med & Populat Genet, Broad Inst, Cambridge, MA 02142 USA

[7] Harvard Univ, Cambridge, MA 02142 USA

[8] Autism Consortium, Boston, MA 02115 USA

[9] Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA

[10] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA

[11] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA

[12] Istanbul Univ, Istanbul Fac Med, Dept Child Psychiat, Istanbul, Turkey

[13] King Faisal Specialist Hosp & Res Ctr, Dept Neurosci & Pediat, Jeddah, Saudi Arabia

[14] Brown Univ, Sch Med, Providence, RI 02912 USA

[15] Combined Mil Hosp, Dept Neurol, Lahore, Pakistan

[16] Kuwait Ctr Autism, Kuwait, Kuwait

[17] Childrens Hosp, Dev Med Ctr, Boston, MA 02115 USA

[18] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA

[19] Rensselaer Polytech Inst, Dept Biol, Troy, NY 12180 USA

来源：

SCIENCE | 2008年 / 321卷 / 5886期

关键词：

D O I：

10.1126/science.1157657

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

To find inherited causes of autism- spectrum disorders, we studied families in which parents share ancestors, enhancing the role of inherited factors. We mapped several loci, some containing large, inherited, homozygous deletions that are likely mutations. The largest deletions implicated genes, including PCDH10 ( protocadherin 10) and DIA1 ( deleted in autism1, or c3orf58), whose level of expression changes in response to neuronal activity, a marker of genes involved in synaptic changes that underlie learning. A subset of genes, including NHE9 (Na+/H+ exchanger 9), showed additional potential mutations in patients with unrelated parents. Our findings highlight the utility of "homozygosity mapping" in heterogeneous disorders like autism but also suggest that defective regulation of gene expression after neural activity may be a mechanism common to seemingly diverse autism mutations.

引用

页码：218 / 223

页数：6

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