Elucidating the genetic architecture of familial schizophrenia using rare copy number variant and linkage scans Export

@article{citeulike:5859393, abstract = {10.1073/pnas.0908584106 To elucidate the genetic architecture of familial schizophrenia we combine linkage analysis with studies of fine-level chromosomal variation in families recruited from the Afrikaner population in South Africa. We demonstrate that individually rare inherited copy number variants (CNVs) are more frequent in cases with familial schizophrenia as compared to unaffected controls and affect almost exclusively genic regions. Interestingly, we find that while the prevalence of rare structural variants is similar in familial and sporadic cases, the type of variants is markedly different. In addition, using a high-density linkage scan with a panel of nearly 2,000 markers, we identify a region on chromosome 13q34 that shows genome-wide significant linkage to schizophrenia and show that in the families not linked to this locus, there is evidence for linkage to chromosome 1p36. No causative CNVs were identified in either locus. Overall, our results from approaches designed to detect risk variants with relatively low frequency and high penetrance in a well-defined and relatively homogeneous population, provide strong empirical evidence supporting the notion that multiple genetic variants, including individually rare ones, that affect many different genes contribute to the genetic risk of familial schizophrenia. They also highlight differences in the genetic architecture of the familial and sporadic forms of the disease.}, author = {Xu, Bin and Woodroffe, Abigail and Rodriguez-Murillo, Laura and Roos, J. Louw and van Rensburg, Elizabeth J. and Abecasis, Gon\~{A}{\S}alo R. and Gogos, Joseph A. and Karayiorgou, Maria}, booktitle = {Proceedings of the National Academy of Sciences}, citeulike-article-id = {5859393}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0908584106}, citeulike-linkout-1 = {http://www.pnas.org/content/106/39/16746.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/106/39/16746.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19805367}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19805367}, day = {29}, doi = {10.1073/pnas.0908584106}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {cnv, example, inheritance, rare, recurrent, teaching}, month = {September}, number = {39}, pages = {16746--16751}, posted-at = {2009-09-30 11:49:02}, priority = {2}, title = {Elucidating the genetic architecture of familial schizophrenia using rare copy number variant and linkage scans}, url = {http://dx.doi.org/10.1073/pnas.0908584106}, volume = {106}, year = {2009} }

TY - JOUR ID - citeulike:5859393 L3 - citeulike-article-id:5859393 N2 - 10.1073/pnas.0908584106 To elucidate the genetic architecture of familial schizophrenia we combine linkage analysis with studies of fine-level chromosomal variation in families recruited from the Afrikaner population in South Africa. We demonstrate that individually rare inherited copy number variants (CNVs) are more frequent in cases with familial schizophrenia as compared to unaffected controls and affect almost exclusively genic regions. Interestingly, we find that while the prevalence of rare structural variants is similar in familial and sporadic cases, the type of variants is markedly different. In addition, using a high-density linkage scan with a panel of nearly 2,000 markers, we identify a region on chromosome 13q34 that shows genome-wide significant linkage to schizophrenia and show that in the families not linked to this locus, there is evidence for linkage to chromosome 1p36. No causative CNVs were identified in either locus. Overall, our results from approaches designed to detect risk variants with relatively low frequency and high penetrance in a well-defined and relatively homogeneous population, provide strong empirical evidence supporting the notion that multiple genetic variants, including individually rare ones, that affect many different genes contribute to the genetic risk of familial schizophrenia. They also highlight differences in the genetic architecture of the familial and sporadic forms of the disease. IS - 39 JF - Proceedings of the National Academy of Sciences of the United States of America SN - 1091-6490 EP - 16751 TI - Elucidating the genetic architecture of familial schizophrenia using rare copy number variant and linkage scans VL - 106 T2 - Proceedings of the National Academy of Sciences SP - 16746 KW - cnv KW - example KW - inheritance KW - rare KW - recurrent KW - teaching AU - Xu, Bin AU - Woodroffe, Abigail AU - Rodriguez-Murillo, Laura AU - Roos, Louw AU - van Rensburg, Elizabeth AU - Abecasis, Gonçalo AU - Gogos, Joseph AU - Karayiorgou, Maria PY - 2009/09/29/ UR - http://dx.doi.org/10.1073/pnas.0908584106 ER -