权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular Genetics of Schizophrenia Susceptibility

精神分裂症易感性的分子遗传学

基本信息

批准号：
7347563
负责人：
Linda M Brzustowicz
金额：
$ 49.73万
依托单位：
RUTGERS, THE STATE UNIV OF N.J.
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-02-01 至 2010-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7347563
关键词：
1q22 Adoption Adult Affect Alternative Splicing Area Base Sequence Brain Canada Chromosomes Code Collection Complementary DNA Complex Diagnosis Disease Family Functional RNA Funding Future Gene Expression General Population Genes Genomics Genotype Goals Hereditary Disease Heritability Human Immunohistochemistry Incidence Individual Introns Investigation Length Link Linkage Disequilibrium Linkage Disequilibrium Mapping Location Maps Methods Modeling Molecular Genetics Mus Northern Blotting Nucleic Acid Regulatory Sequences Polymerase Chain Reaction Population Study Predisposition Prefrontal Cortex Protein Analysis Proteins RNA RNA analysis Rattus Relative (related person)Reporting Sampling Schizoaffective Disorders Schizophrenia Screening procedure Signal Transduction Susceptibility Gene Techniques Testing Tetraodontidae Time Transcript Twin Multiple Birth Variant Western Blotting cDNA Library case control comparative fetal genetic linkage analysis genetic pedigree interest lymphoblastoid cell line neuropsychiatry protein distribution research study segregation simulation size

项目摘要

DESCRIPTION (provided by applicant): Schizophrenia is a serious neuropsychiatric illness estimated to affect approximately 1% of the general population. Family, twin and adoption studies have demonstrated that schizophrenia is predominantly a genetic disorder, with a high heritability. Segregation analyses have failed to clearly support a single model of inheritance and suggest at least several, possibly interacting, susceptibility loci. We have previously identified a strong linkage signal (hlod=6.5, empirical p less than 0.0002) to 1q22 in a set of medium-sized Canadian families, selected for study because multiple relatives were clinically diagnosed with schizophrenia or schizoaffective disorder. Fine-map linkage analysis has identified an approximately 1.3 Mb interval that appears very likely to harbor the susceptibility gene, with a 300 kb sub-region identified by linkage as most likely to contain the gene. We have further identified significant linkage disequilibrium (LD) within a 100 kb portion of this sub-interval. The region of LD is contained within the over 300 kb genomic extent of the gene ICAPON, and there is evidence that additional genes may exist within the introns of this large gene. We plan to search this region for additional transcribed sequences to screen for variants associated with schizophrenia susceptibility. We also plan to use comparative genomic techniques to identify conserved regulatory regions within this area. These will also be assessed for variation that is associated with schizophrenia susceptibility. The sample with strong linkage to this region will first be tested for LD, with the NIMH-HGI collection and a Canadian case-control sample also genotyped with markers producing significant LD in the linkage sample. We also plan to conduct expression studies of protein and RNA, using RNA from the Stanley Array Collection, post-mortem brains from the Harvard Brain Bank, and lymphoblastoid cell lines from our linkage sample and the NIMH-HGI collection. We hope to use our investigations of this locus in this sample as a testbed for refining a comprehensive approach to susceptibility gene identification, combining linkage and linkage disequilibrium mapping, evolutionary based sequence comparison methods, and complementary gene expression studies. We anticipate that these methods will be of future use for finding additional susceptibility genes for schizophrenia and other complex disorders.

描述（由申请人提供）：

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Copy number variations in schizophrenia: critical review and new perspectives on concepts of genetics and disease.

DOI：
10.1176/appi.ajp.2009.09071016
发表时间：
2010-08
期刊：
The American journal of psychiatry
影响因子：
0
作者：
Bassett AS;Scherer SW;Brzustowicz LM
通讯作者：
Brzustowicz LM

Childhood trauma and genetic factors in familial schizophrenia associated with the NOS1AP gene.

与NOS1AP基因相关的家族性精神分裂症的儿童创伤和遗传因素。

DOI：
10.1016/j.schres.2010.05.021
发表时间：
2010-08
期刊：
SCHIZOPHRENIA RESEARCH
影响因子：
4.5
作者：
Husted, Janice A.;Ahmed, Rashid;Chow, Eva W. C.;Brzustowicz, Linda M.;Bassett, Anne S.
通讯作者：
Bassett, Anne S.

Schizophrenia and genetics: new insights.

DOI：
10.1007/s11920-996-0051-x
发表时间：
2002-08-01
期刊：
Current psychiatry reports
影响因子：
6.7
作者：
Bassett, Anne S;Chow, Eva W;Brzustowicz, Linda
通讯作者：
Brzustowicz, Linda

Early environmental exposures influence schizophrenia expression even in the presence of strong genetic predisposition.

DOI：
10.1016/j.schres.2012.02.009
发表时间：
2012-05
期刊：
SCHIZOPHRENIA RESEARCH
影响因子：
4.5
作者：
Husted, Janice A.;Ahmed, Rashid;Chow, Eva W. C.;Brzustowicz, Linda M.;Bassett, Anne S.
通讯作者：
Bassett, Anne S.

Identification of a schizophrenia-associated functional noncoding variant in NOS1AP.

DOI：
10.1176/appi.ajp.2008.08081266
发表时间：
2009-04
期刊：
The American journal of psychiatry
影响因子：
0
作者：
Wratten NS;Memoli H;Huang Y;Dulencin AM;Matteson PG;Cornacchia MA;Azaro MA;Messenger J;Hayter JE;Bassett AS;Buyske S;Millonig JH;Vieland VJ;Brzustowicz LM
通讯作者：
Brzustowicz LM