The Experts below are selected from a list of 42444 Experts worldwide ranked by ideXlab platform
Michael L Klein - One of the best experts on this subject based on the ideXlab platform.
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expanded genome scan in Extended Families with age related macular degeneration
Investigative Ophthalmology & Visual Science, 2006Co-Authors: Jacek Majewski, Dennis W Schultz, Richard G Weleber, Mitchell B Schain, Ted S Acott, Jurg Ott, Michael L Klein, Sandra Barral, Peter J Francis, Chad HaynesAbstract:PURPOSE. To investigate further the genetic contribution to age-related macular degeneration (AMD), increasing the power of a previous analysis and reproducing the original findings. METHODS. A large cohort of Families with this condition was assembled, and an expanded genome scan was performed with 556 microsatellite markers. In 2003, the results were reported of a genome-wide linkage analysis of 70 of these pedigrees. Members of 51 new Families have now been ascertained and many of the original pedigrees expanded. Parametric and nonparametric linkage analyses were performed with a denser map of markers. In addition, analyses were performed with the sample stratified by age at ascertainment and by two major advanced phenotypes for the disease: neovascular AMD (choroidal neovascularization) and geographic atrophy. RESULTS. The results corroborate the macular degeneration‐ susceptibility loci consistently reported by the authors and others in genome-wide scans. New loci were identified, including the finding of a two-point HLOD of 3.70 at 6q25.2. CONCLUSIONS. The results suggest that the use of Families enriched in predisposition to AMD has legitimacy. Genetic analyses of a genome-wide scan performed on our large cohort of Families add further confirmatory evidence that susceptibility loci lie on 1q, 3p, 9q, and 10q. Furthermore, new loci have been identified, including a locus on 6q. (Invest Ophthalmol Vis Sci. 2006;47:5453‐5459) DOI:10.1167/iovs.06-0655
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age related macular degeneration a genome scan in Extended Families
American Journal of Human Genetics, 2003Co-Authors: Jacek Majewski, Dennis W Schultz, Richard G Weleber, Mitchell B Schain, Albert O Edwards, Tara C Matise, Ted S Acott, Jurg Ott, Michael L KleinAbstract:We performed a genomewide scan and genetic linkage analysis, to identify loci associated with age-related macular degeneration (AMD). We collected 70 Families, ranging from small nuclear Families to Extended multigenerational pedigrees and consisting of a total of 344 affected and 217 unaffected members available for genotyping. We performed linkage analyses using parametric and allele-sharing models. We performed the analyses on the complete pedigrees but also subdivided the Families into nuclear pedigrees. Finally, to dissect potential genetic factors responsible for differences in disease manifestation, we stratified the sample by two major AMD phenotypes (neovascular AMD and geographic atrophy) and by age of affected family members at the time of our evaluation. We have previously demonstrated linkage between AMD and 1q25-31 in a single large family. In the combined sample, we have detected the following loci with scores exceeding a LOD=2 cutoff under at least one of the models considered: 1q31 (HLOD=2.07 at D1S518), 3p13 (HLOD=2.19 at D3S1304/D3S4545), 4q32 (HLOD=2.66 at D4S2368, for the subset of Families with predominantly dry AMD), 9q33 (LODZlr=2.01 at D9S930/D9S934), and 10q26 (HLOD=3.06 at D10S1230). Using correlation analysis, we have found a statistically significant correlation between LOD scores at 3p13 and 10q26, providing evidence for epistatic interactions between the loci and, hence, a complex basis of AMD. Our study has identified new loci that should be considered in future mapping and mutational analyses of AMD and has strengthened the evidence in support of loci suggested by other studies.
Jacek Majewski - One of the best experts on this subject based on the ideXlab platform.
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expanded genome scan in Extended Families with age related macular degeneration
Investigative Ophthalmology & Visual Science, 2006Co-Authors: Jacek Majewski, Dennis W Schultz, Richard G Weleber, Mitchell B Schain, Ted S Acott, Jurg Ott, Michael L Klein, Sandra Barral, Peter J Francis, Chad HaynesAbstract:PURPOSE. To investigate further the genetic contribution to age-related macular degeneration (AMD), increasing the power of a previous analysis and reproducing the original findings. METHODS. A large cohort of Families with this condition was assembled, and an expanded genome scan was performed with 556 microsatellite markers. In 2003, the results were reported of a genome-wide linkage analysis of 70 of these pedigrees. Members of 51 new Families have now been ascertained and many of the original pedigrees expanded. Parametric and nonparametric linkage analyses were performed with a denser map of markers. In addition, analyses were performed with the sample stratified by age at ascertainment and by two major advanced phenotypes for the disease: neovascular AMD (choroidal neovascularization) and geographic atrophy. RESULTS. The results corroborate the macular degeneration‐ susceptibility loci consistently reported by the authors and others in genome-wide scans. New loci were identified, including the finding of a two-point HLOD of 3.70 at 6q25.2. CONCLUSIONS. The results suggest that the use of Families enriched in predisposition to AMD has legitimacy. Genetic analyses of a genome-wide scan performed on our large cohort of Families add further confirmatory evidence that susceptibility loci lie on 1q, 3p, 9q, and 10q. Furthermore, new loci have been identified, including a locus on 6q. (Invest Ophthalmol Vis Sci. 2006;47:5453‐5459) DOI:10.1167/iovs.06-0655
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age related macular degeneration a genome scan in Extended Families
American Journal of Human Genetics, 2003Co-Authors: Jacek Majewski, Dennis W Schultz, Richard G Weleber, Mitchell B Schain, Albert O Edwards, Tara C Matise, Ted S Acott, Jurg Ott, Michael L KleinAbstract:We performed a genomewide scan and genetic linkage analysis, to identify loci associated with age-related macular degeneration (AMD). We collected 70 Families, ranging from small nuclear Families to Extended multigenerational pedigrees and consisting of a total of 344 affected and 217 unaffected members available for genotyping. We performed linkage analyses using parametric and allele-sharing models. We performed the analyses on the complete pedigrees but also subdivided the Families into nuclear pedigrees. Finally, to dissect potential genetic factors responsible for differences in disease manifestation, we stratified the sample by two major AMD phenotypes (neovascular AMD and geographic atrophy) and by age of affected family members at the time of our evaluation. We have previously demonstrated linkage between AMD and 1q25-31 in a single large family. In the combined sample, we have detected the following loci with scores exceeding a LOD=2 cutoff under at least one of the models considered: 1q31 (HLOD=2.07 at D1S518), 3p13 (HLOD=2.19 at D3S1304/D3S4545), 4q32 (HLOD=2.66 at D4S2368, for the subset of Families with predominantly dry AMD), 9q33 (LODZlr=2.01 at D9S930/D9S934), and 10q26 (HLOD=3.06 at D10S1230). Using correlation analysis, we have found a statistically significant correlation between LOD scores at 3p13 and 10q26, providing evidence for epistatic interactions between the loci and, hence, a complex basis of AMD. Our study has identified new loci that should be considered in future mapping and mutational analyses of AMD and has strengthened the evidence in support of loci suggested by other studies.
Ahmad Sukari Halim - One of the best experts on this subject based on the ideXlab platform.
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two novel genes tox3 and col21a1 in large Extended malay Families with nonsyndromic cleft lip and or palate
Molecular Genetics & Genomic Medicine, 2019Co-Authors: Nurul Syazana Mohamad Shah, Sarina Sulong, Wan Azman Wan Sulaiman, Ahmad Sukari HalimAbstract:BACKGROUND Nonsyndromic cleft lip and/or palate is one of the most common human birth defects worldwide that affects the lip and/or palate. The incidence of clefts varies among populations through ethnic, race, or geographical differences. The focus on Malay nonsyndromic cleft lip and/or palate (NSCL/P) is because of a scarce report on genetic study in relation to this deformity in Malaysia. We are interested to discuss about the genes that are susceptible to cause orofacial cleft formation in the family. METHODS Genome-wide linkage analysis was carried out on eight large Extended Families of NSCL/P with the total of 91 individuals among Malay population using microarray platform. Based on linkage analyses findings, copy number variation (CNV) of LPHN2, SATB2, PVRL3, COL21A1, and TOX3 were identified in four large Extended Families that showed linkage evidence using quantitative polymerase chain reaction (qPCR) as for a validation purpose. Copy number calculated (CNC) for each genes were determined with Applied Biosystems CopyCallerTM Software v2.0. Normal CNC of the target sequence expected was set at two. RESULTS Genome-wide linkage analysis had discovered several genes including TOX3 and COL21A1 in four different loci 4p15.2-p16.1, 6p11.2-p12.3, 14q13-q21, and 16q12.1. There was significant decreased, p < 0.05 of SATB2, COL21A1, and TOX3 copy number in Extended Families compared to the normal controls. CONCLUSION Novel linkage evidence and significant low copy number of COL21A1 and TOX3 in NSCLP family was confirmed. These genes increased the risks toward NSCLP formation in that family traits.
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discovery of candidate genes for nonsyndromic cleft lip palate through genome wide linkage analysis of large Extended Families in the malay population
BMC Genetics, 2016Co-Authors: Nurul Syazana Mohamad Shah, Iman Salahshourifar, Sarina Sulong, Wan Azman Wan Sulaiman, Ahmad Sukari HalimAbstract:Nonsyndromic orofacial clefts are one of the most common birth defects worldwide. It occurs as a result of genetic or environmental factors. This study investigates the genetic contribution to nonsyndromic cleft lip and/or palate through the analysis of family pedigrees. Candidate genes associated with the condition were identified from large Extended Families from the Malay population. A significant nonparametric linkage (NPL) score was detected in family 100. Other suggestive NPL and logarithm of the odds (LOD) scores were attained from Families 50, 58, 99 and 100 under autosomal recessive mode. Heterogeneity LOD (HLOD) score ≥ 1 was determined for all Families, confirming genetic heterogeneity of the population and indicating that a proportion of Families might be linked to each other. Several candidate genes in linkage intervals were determined; LPHN2 at 1p31, SATB2 at 2q33.1-q35, PVRL3 at 3q13.3, COL21A1 at 6p12.1, FOXP2 at 7q22.3-q33, FOXG1 and HECTD1 at 14q12 and TOX3 at 16q12.1. We have identified several novel and known candidate genes for nonsyndromic cleft lip and/or palate through genome-wide linkage analysis. Further analysis of the involvement of these genes in the condition will shed light on the disease mechanism. Comprehensive genetic testing of the candidate genes is warranted.
Jurg Ott - One of the best experts on this subject based on the ideXlab platform.
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expanded genome scan in Extended Families with age related macular degeneration
Investigative Ophthalmology & Visual Science, 2006Co-Authors: Jacek Majewski, Dennis W Schultz, Richard G Weleber, Mitchell B Schain, Ted S Acott, Jurg Ott, Michael L Klein, Sandra Barral, Peter J Francis, Chad HaynesAbstract:PURPOSE. To investigate further the genetic contribution to age-related macular degeneration (AMD), increasing the power of a previous analysis and reproducing the original findings. METHODS. A large cohort of Families with this condition was assembled, and an expanded genome scan was performed with 556 microsatellite markers. In 2003, the results were reported of a genome-wide linkage analysis of 70 of these pedigrees. Members of 51 new Families have now been ascertained and many of the original pedigrees expanded. Parametric and nonparametric linkage analyses were performed with a denser map of markers. In addition, analyses were performed with the sample stratified by age at ascertainment and by two major advanced phenotypes for the disease: neovascular AMD (choroidal neovascularization) and geographic atrophy. RESULTS. The results corroborate the macular degeneration‐ susceptibility loci consistently reported by the authors and others in genome-wide scans. New loci were identified, including the finding of a two-point HLOD of 3.70 at 6q25.2. CONCLUSIONS. The results suggest that the use of Families enriched in predisposition to AMD has legitimacy. Genetic analyses of a genome-wide scan performed on our large cohort of Families add further confirmatory evidence that susceptibility loci lie on 1q, 3p, 9q, and 10q. Furthermore, new loci have been identified, including a locus on 6q. (Invest Ophthalmol Vis Sci. 2006;47:5453‐5459) DOI:10.1167/iovs.06-0655
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age related macular degeneration a genome scan in Extended Families
American Journal of Human Genetics, 2003Co-Authors: Jacek Majewski, Dennis W Schultz, Richard G Weleber, Mitchell B Schain, Albert O Edwards, Tara C Matise, Ted S Acott, Jurg Ott, Michael L KleinAbstract:We performed a genomewide scan and genetic linkage analysis, to identify loci associated with age-related macular degeneration (AMD). We collected 70 Families, ranging from small nuclear Families to Extended multigenerational pedigrees and consisting of a total of 344 affected and 217 unaffected members available for genotyping. We performed linkage analyses using parametric and allele-sharing models. We performed the analyses on the complete pedigrees but also subdivided the Families into nuclear pedigrees. Finally, to dissect potential genetic factors responsible for differences in disease manifestation, we stratified the sample by two major AMD phenotypes (neovascular AMD and geographic atrophy) and by age of affected family members at the time of our evaluation. We have previously demonstrated linkage between AMD and 1q25-31 in a single large family. In the combined sample, we have detected the following loci with scores exceeding a LOD=2 cutoff under at least one of the models considered: 1q31 (HLOD=2.07 at D1S518), 3p13 (HLOD=2.19 at D3S1304/D3S4545), 4q32 (HLOD=2.66 at D4S2368, for the subset of Families with predominantly dry AMD), 9q33 (LODZlr=2.01 at D9S930/D9S934), and 10q26 (HLOD=3.06 at D10S1230). Using correlation analysis, we have found a statistically significant correlation between LOD scores at 3p13 and 10q26, providing evidence for epistatic interactions between the loci and, hence, a complex basis of AMD. Our study has identified new loci that should be considered in future mapping and mutational analyses of AMD and has strengthened the evidence in support of loci suggested by other studies.
Ted S Acott - One of the best experts on this subject based on the ideXlab platform.
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expanded genome scan in Extended Families with age related macular degeneration
Investigative Ophthalmology & Visual Science, 2006Co-Authors: Jacek Majewski, Dennis W Schultz, Richard G Weleber, Mitchell B Schain, Ted S Acott, Jurg Ott, Michael L Klein, Sandra Barral, Peter J Francis, Chad HaynesAbstract:PURPOSE. To investigate further the genetic contribution to age-related macular degeneration (AMD), increasing the power of a previous analysis and reproducing the original findings. METHODS. A large cohort of Families with this condition was assembled, and an expanded genome scan was performed with 556 microsatellite markers. In 2003, the results were reported of a genome-wide linkage analysis of 70 of these pedigrees. Members of 51 new Families have now been ascertained and many of the original pedigrees expanded. Parametric and nonparametric linkage analyses were performed with a denser map of markers. In addition, analyses were performed with the sample stratified by age at ascertainment and by two major advanced phenotypes for the disease: neovascular AMD (choroidal neovascularization) and geographic atrophy. RESULTS. The results corroborate the macular degeneration‐ susceptibility loci consistently reported by the authors and others in genome-wide scans. New loci were identified, including the finding of a two-point HLOD of 3.70 at 6q25.2. CONCLUSIONS. The results suggest that the use of Families enriched in predisposition to AMD has legitimacy. Genetic analyses of a genome-wide scan performed on our large cohort of Families add further confirmatory evidence that susceptibility loci lie on 1q, 3p, 9q, and 10q. Furthermore, new loci have been identified, including a locus on 6q. (Invest Ophthalmol Vis Sci. 2006;47:5453‐5459) DOI:10.1167/iovs.06-0655
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age related macular degeneration a genome scan in Extended Families
American Journal of Human Genetics, 2003Co-Authors: Jacek Majewski, Dennis W Schultz, Richard G Weleber, Mitchell B Schain, Albert O Edwards, Tara C Matise, Ted S Acott, Jurg Ott, Michael L KleinAbstract:We performed a genomewide scan and genetic linkage analysis, to identify loci associated with age-related macular degeneration (AMD). We collected 70 Families, ranging from small nuclear Families to Extended multigenerational pedigrees and consisting of a total of 344 affected and 217 unaffected members available for genotyping. We performed linkage analyses using parametric and allele-sharing models. We performed the analyses on the complete pedigrees but also subdivided the Families into nuclear pedigrees. Finally, to dissect potential genetic factors responsible for differences in disease manifestation, we stratified the sample by two major AMD phenotypes (neovascular AMD and geographic atrophy) and by age of affected family members at the time of our evaluation. We have previously demonstrated linkage between AMD and 1q25-31 in a single large family. In the combined sample, we have detected the following loci with scores exceeding a LOD=2 cutoff under at least one of the models considered: 1q31 (HLOD=2.07 at D1S518), 3p13 (HLOD=2.19 at D3S1304/D3S4545), 4q32 (HLOD=2.66 at D4S2368, for the subset of Families with predominantly dry AMD), 9q33 (LODZlr=2.01 at D9S930/D9S934), and 10q26 (HLOD=3.06 at D10S1230). Using correlation analysis, we have found a statistically significant correlation between LOD scores at 3p13 and 10q26, providing evidence for epistatic interactions between the loci and, hence, a complex basis of AMD. Our study has identified new loci that should be considered in future mapping and mutational analyses of AMD and has strengthened the evidence in support of loci suggested by other studies.
