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Genomewide Scan and Fine-Mapping Linkage Studies in Four European Samples with Bipolar Affective Disorder Suggest a New Susceptibility Locus on Chromosome.

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Presentation on theme: "Genomewide Scan and Fine-Mapping Linkage Studies in Four European Samples with Bipolar Affective Disorder Suggest a New Susceptibility Locus on Chromosome."— Presentation transcript:

1 Genomewide Scan and Fine-Mapping Linkage Studies in Four European Samples with Bipolar Affective Disorder Suggest a New Susceptibility Locus on Chromosome 1p35- p36 and Provides Further Evidence of Loci on Chromosome 4q31 and 6q24  Johannes Schumacher, Radka Kaneva, Rami Abou Jamra, Guillermo Orozco Diaz, Stephanie Ohlraun, Vihra Milanova, Young-Ae Lee, Fabio Rivas, Fermin Mayoral, Robert Fuerst, Antonia Flaquer, Christine Windemuth, Eudoxia Gay, Sebastian Sanz, Maria José González, Susana Gil, Francisco Cabaleiro, Francisco del Rio, Fermin Perez, Jesus Haro, Christian Kostov, Vesselin Chorbov, Amelia Nikolova-Hill, Vessela Stoyanova, George Onchev, Ivo Kremensky, Konstantin Strauch, Thomas G. Schulze, Peter Nürnberg, Wolfgang Gaebel, Ansgar Klimke, Georg Auburger, Thomas F. Wienker, Luba Kalaydjieva, Peter Propping, Sven Cichon, Assen Jablensky, Marcella Rietschel, Markus M. Nöthen  The American Journal of Human Genetics  Volume 77, Issue 6, Pages (December 2005) DOI: /498619 Copyright © 2005 The American Society of Human Genetics Terms and Conditions

2 Figure 1 Genomewide scan: multipoint NPL analysis of ASDI, ASDII, and ASDIII, across all chromosomes in the entire linkage sample. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

3 Figure 1 Genomewide scan: multipoint NPL analysis of ASDI, ASDII, and ASDIII, across all chromosomes in the entire linkage sample. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

4 Figure 1 Genomewide scan: multipoint NPL analysis of ASDI, ASDII, and ASDIII, across all chromosomes in the entire linkage sample. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

5 Figure 2 Genomewide scan: multipoint NPL analysis of ASDI, ASDII, and ASDIII, across all chromosomes in the Spanish linkage sample. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

6 Figure 2 Genomewide scan: multipoint NPL analysis of ASDI, ASDII, and ASDIII, across all chromosomes in the Spanish linkage sample. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

7 Figure 2 Genomewide scan: multipoint NPL analysis of ASDI, ASDII, and ASDIII, across all chromosomes in the Spanish linkage sample. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

8 Figure 3 Genomewide scan: multipoint NPL analysis of ASDI, ASDII, and ASDIII, across all chromosomes in the Romany linkage sample. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

9 Figure 3 Genomewide scan: multipoint NPL analysis of ASDI, ASDII, and ASDIII, across all chromosomes in the Romany linkage sample. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

10 Figure 3 Genomewide scan: multipoint NPL analysis of ASDI, ASDII, and ASDIII, across all chromosomes in the Romany linkage sample. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

11 Figure 4 Genomewide scan: multipoint NPL analysis of ASDI, ASDII, and ASDIII, across all chromosomes in the Bulgarian linkage sample. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

12 Figure 4 Genomewide scan: multipoint NPL analysis of ASDI, ASDII, and ASDIII, across all chromosomes in the Bulgarian linkage sample. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

13 Figure 4 Genomewide scan: multipoint NPL analysis of ASDI, ASDII, and ASDIII, across all chromosomes in the Bulgarian linkage sample. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

14 Figure 5 Fine-mapping linkage analysis: chromosomal 1p34-p36 multipoint NPL results in the fine-mapping sample and in the Spanish, Romany, and Bulgarian subsamples of ASDI, ASDII, and ASDIII. The legend is available in its entirety in the online edition of The American Journal of Human Genetics. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

15 Figure 5 Fine-mapping linkage analysis: chromosomal 1p34-p36 multipoint NPL results in the fine-mapping sample and in the Spanish, Romany, and Bulgarian subsamples of ASDI, ASDII, and ASDIII. The legend is available in its entirety in the online edition of The American Journal of Human Genetics. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

16 Figure 5 Fine-mapping linkage analysis: chromosomal 1p34-p36 multipoint NPL results in the fine-mapping sample and in the Spanish, Romany, and Bulgarian subsamples of ASDI, ASDII, and ASDIII. The legend is available in its entirety in the online edition of The American Journal of Human Genetics. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

17 Figure 6 Plot of the MOD score for chromosome 1p35-p36, with a separate maximization over trait-model parameters for each genetic position assumed for the trait locus. ASDI (red) position of the maximum MOD score: cM; penetrances {0.00; 0.49; 0.49}; disease-allele frequency ASDII (green) position of the maximum MOD score: cM; penetrances {0.00; 0.50; 0.50}; disease-allele frequency ASDIII (blue) position of the maximum MOD score: cM; penetrances {0.00; 0.53; 0.53}; disease-allele frequency MOD scores are determined from the deCODE Genetics sex-averaged map. The penetrance of the disease models is obtained by MOD-score analysis and given in order {f+/+; fm/+; fm/m}. A plus sign (+) indicates the wild-type allele; “m” indicates the mutant allele. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

18 Figure 7 Fine-mapping linkage analysis: chromosomal 4q28-4q31 multipoint NPL results in the fine-mapping sample and in the German, Romany, and Bulgarian subsamples of ASDI, ASDII, and ASDIII. The legend is available in its entirety in the online edition of The American Journal of Human Genetics. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

19 Figure 7 Fine-mapping linkage analysis: chromosomal 4q28-4q31 multipoint NPL results in the fine-mapping sample and in the German, Romany, and Bulgarian subsamples of ASDI, ASDII, and ASDIII. The legend is available in its entirety in the online edition of The American Journal of Human Genetics. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

20 Figure 7 Fine-mapping linkage analysis: chromosomal 4q28-4q31 multipoint NPL results in the fine-mapping sample and in the German, Romany, and Bulgarian subsamples of ASDI, ASDII, and ASDIII. The legend is available in its entirety in the online edition of The American Journal of Human Genetics. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

21 Figure 8 Plot of the MOD score for chromosome 4q31, with a separate maximization over trait-model parameters for each genetic position assumed for the trait locus. ASDI (red) position of the maximum MOD score: cM; penetrances {0.00; 0.30; 0.92}; disease-allele frequency ASDII (green) position of the maximum MOD score: cM; penetrances {0.00; 0.33; 0.99}; disease-allele frequency ASDIII (blue) position of the maximum MOD score: cM; penetrances {0.00; 0.49; 0.96}; disease-allele frequency MOD scores are determined from the deCODE Genetics sex-averaged map. The penetrance of the disease models is obtained by MOD-score analysis and given in order {f+/+; fm/+; fm/m}. A plus sign (+) indicates the wild-type allele; “m” indicates the mutant allele. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

22 Figure 9 Fine-mapping linkage analysis: chromosomal 6q15-q24 multipoint NPL results in the fine-mapping sample and in the German, Romany, Spanish, and Bulgarian subsamples of ASDI, ASDII, and ASDIII. The legend is available in its entirety in the online edition of The American Journal of Human Genetics. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

23 Figure 9 Fine-mapping linkage analysis: chromosomal 6q15-q24 multipoint NPL results in the fine-mapping sample and in the German, Romany, Spanish, and Bulgarian subsamples of ASDI, ASDII, and ASDIII. The legend is available in its entirety in the online edition of The American Journal of Human Genetics. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

24 Figure 9 Fine-mapping linkage analysis: chromosomal 6q15-q24 multipoint NPL results in the fine-mapping sample and in the German, Romany, Spanish, and Bulgarian subsamples of ASDI, ASDII, and ASDIII. The legend is available in its entirety in the online edition of The American Journal of Human Genetics. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

25 Figure 10 Plot of the MOD score for chromosome 6q24, with a separate maximization over trait-model parameters for each genetic position assumed for the trait locus. ASDI (red) position of the maximum MOD score: cM; penetrances {0.00; 0.50; 0.50}; disease-allele frequency ASDII (green) position of the maximum MOD score: cM; penetrances {0.00; 0.52; 0.52}; disease-allele frequency ASDIII (blue) position of the maximum MOD score: cM; penetrances {0.00; 0.11; 0.26}; disease-allele frequency MOD scores are determined from the deCODE Genetics sex-averaged map. The penetrance of the disease models is obtained by MOD-score analysis and given in order {f+/+; fm/+; fm/m}. A plus sign (+) indicates the wild-type allele; “m” indicates the mutant allele. The American Journal of Human Genetics  , DOI: ( /498619) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

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