The Experts below are selected from a list of 33 Experts worldwide ranked by ideXlab platform
Gabriella Lindgren - One of the best experts on this subject based on the ideXlab platform.
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Multiple congenital ocular anomalies in Icelandic Horses
BMC Veterinary Research, 2011Co-Authors: Lisa S Andersson, Gabriella Lindgren, Jeanette Axelsson, Richard R. Dubielzig, Björn EkestenAbstract:Background Multiple congenital ocular anomalies (MCOA) syndrome is a hereditary congenital eye defect that was first described in Silver colored Rocky Mountain Horses. The mutation causing this disease is located within a defined chromosomal interval, which also contains the gene and mutation that is associated with the Silver coat color ( PMEL17 , exon 11). Horses that are homozygous for the disease-causing allele have multiple defects (MCOA-phenotype), whilst the heterozygous Horses predominantly have cysts of the iris, ciliary body or retina (Cyst-phenotype). It has been argued that these ocular defects are caused by a recent mutation that is restricted to Horses that are related to the Rocky Mountain Horse breed. For that reason we have examined another Horse breed, the Icelandic Horse, which is historically quite divergent from Rocky Mountain Horses. Results We examined 24 Icelandic Horses and established that the MCOA syndrome is present in this breed. Four of these Horses were categorised as having the MCOA-phenotype and were genotyped as being homozygous for the PMEL17 mutation. The most common clinical signs included megaloglobus, iris stromal hypoplasia, abnormal pectinate ligaments, iridociliary cysts occasionally extending into the peripheral retina and cataracts. The cysts and pectinate ligament abnormalities were observed in the temporal quadrant of the eyes. Fourteen Horses were heterozygous for the PMEL17 mutation and were characterized as having the Cyst-phenotype with cysts and occasionally curvilinear streaks in the peripheral retina. Three additional Horses were genotyped as PMEL17 heterozygotes, but in these Horses we were unable to detect cysts or other forms of anomalies. One eye of a severely vision-impaired 18 month-old stallion, homozygous for the PMEL17 mutation was examined by light microscopy. Redundant duplication of non-pigmented ciliary body epithelium, sometimes forming cysts bulging into the posterior chamber and localized areas of atrophy in the peripheral retina were seen. Conclusions The MCOA syndrome is segregating with the PMEL17 mutation in the Icelandic Horse population. This needs to be taken into consideration in breeding decisions and highlights the fact that MCOA syndrome is present in a breed that are more ancient and not closely related to the Rocky Mountain Horse breed.
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Multiple congenital ocular anomalies in Icelandic Horses
BMC Veterinary Research, 2011Co-Authors: Lisa S Andersson, Gabriella Lindgren, Jeanette Axelsson, Richard R. Dubielzig, Björn EkestenAbstract:Background Multiple congenital ocular anomalies (MCOA) syndrome is a hereditary congenital eye defect that was first described in Silver colored Rocky Mountain Horses. The mutation causing this disease is located within a defined chromosomal interval, which also contains the gene and mutation that is associated with the Silver coat color (PMEL17, exon 11). Horses that are homozygous for the disease-causing allele have multiple defects (MCOA-phenotype), whilst the heterozygous Horses predominantly have cysts of the iris, ciliary body or retina (Cyst-phenotype). It has been argued that these ocular defects are caused by a recent mutation that is restricted to Horses that are related to the Rocky Mountain Horse breed. For that reason we have examined another Horse breed, the Icelandic Horse, which is historically quite divergent from Rocky Mountain Horses.
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Targeted analysis of four breeds narrows equine Multiple Congenital Ocular Anomalies locus to 208 kilobases
Mammalian Genome, 2011Co-Authors: Lisa S Andersson, Rytis Juras, David T Ramsey, Susan Ewart, Gus Cothran, Björn Ekesten, Katarina Lyberg, Sofia Mikko, Gabriella LindgrenAbstract:The syndrome Multiple Congenital Ocular Anomalies (MCOA) is the collective name ascribed to heritable congenital eye defects in Horses. Individuals homozygous for the disease allele (MCOA phenotype) have a wide range of eye anomalies, while heterozygous Horses (Cyst phenotype) predominantly have cysts that originate from the temporal ciliary body, iris, and/or peripheral retina. MCOA syndrome is highly prevalent in the Rocky Mountain Horse but the disease is not limited to this breed. Affected Horses most often have a Silver coat color; however, a pleiotropic link between these phenotypes is yet to be proven. Locating and possibly isolating these traits would provide invaluable knowledge to scientists and breeders. This would favor maintenance of a desirable coat color while addressing the health concerns of the affected breeds, and would also provide insight into the genetic basis of the disease. Identical-by-descent mapping was used to narrow the previous 4.6-Mb region to a 264-kb interval for the MCOA locus. One haplotype common to four breeds showed complete association to the disease (Cyst phenotype, n = 246; MCOA phenotype, n = 83). Candidate genes from the interval, SMARCC2 and IKZF4 , were screened for polymorphisms and genotyped, and segregation analysis allowed the MCOA syndrome region to be shortened to 208 kb. This interval also harbors PMEL17 , the gene causative for Silver coat color. However, by shortening the MCOA locus by a factor of 20, 176 other genes have been unlinked from the disease and only 15 genes remain.
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Equine Multiple Congenital Ocular Anomalies maps to a 4.9 megabase interval on Horse chromosome 6
BMC Genetics, 2008Co-Authors: Lisa S Andersson, Rytis Juras, David T Ramsey, Jessica Eason-butler, Susan Ewart, Gus Cothran, Gabriella LindgrenAbstract:Background Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome consists of a diverse set of abnormalities predominantly localized to the frontal part of the eye. The disease is in agreement with a codominant mode of inheritance in our Horse material. Animals presumed to be heterozygous for the mutant allele have cysts originating from the temporal ciliary body, peripheral retina and/or iris. In contrast, animals predicted to be homozygous for the disease-causing allele possess a wide range of multiple abnormalities, including iridociliary and/or peripheral retinal cysts, iridocorneal angle abnormalities, cornea globosa, iris hypoplasia and congenital cataracts. MCOA is most common in the Rocky Mountain Horse breed where it occurs at a high frequency among Silver colored Horses. The Silver coat color is associated with mutations in PMEL17 that resides on ECA6q23. To map the MCOA locus we analyzed 11 genetic markers on ECA6q and herein describe a chromosome interval for the MCOA locus. Results We performed linkage analysis within 17 paternal half-sib families of the Rocky Mountain Horse breed. More than half of the 131 offspring had the Cyst phenotype and about one third had MCOA. Segregation data were obtained by genotyping 10 microsatellite markers most of which are positioned on ECA6q22-23, as well as the missense mutation for the Silver phenotype in PMEL17 . Significant linkage was found between the MCOA locus and eight of the genetic markers, where marker UPP5 (Theta = 0, z = 12.3), PMEL17ex11 (Theta = 0, z = 19.0) and UPP6 (Theta = 0, z = 17.5) showed complete linkage with the MCOA locus. DNA sequencing of PMEL17 in affected and healthy control individuals did not reveal any additional mutations than the two mutations associated with the Silver coat color. Conclusion The MCOA locus can with high confidence be positioned within a 4.9 megabase (Mb) interval on ECA6q. The genotype data on UPP5 , PMEL17ex11 and UPP6 strongly support the hypothesis that Horses with the Cyst phenotype are heterozygous for the mutant allele and that Horses with the MCOA phenotype are homozygous for the mutant allele.
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Equine Multiple Congenital Ocular Anomalies maps to a 4.9 megabase interval on Horse chromosome 6
BMC Genetics, 2008Co-Authors: Lisa S Andersson, Rytis Juras, David T Ramsey, Jessica Eason-butler, Susan Ewart, Gus Cothran, Gabriella LindgrenAbstract:Background Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome consists of a diverse set of abnormalities predominantly localized to the frontal part of the eye. The disease is in agreement with a codominant mode of inheritance in our Horse material. Animals presumed to be heterozygous for the mutant allele have cysts originating from the temporal ciliary body, peripheral retina and/or iris. In contrast, animals predicted to be homozygous for the disease-causing allele possess a wide range of multiple abnormalities, including iridociliary and/or peripheral retinal cysts, iridocorneal angle abnormalities, cornea globosa, iris hypoplasia and congenital cataracts. MCOA is most common in the Rocky Mountain Horse breed where it occurs at a high frequency among Silver colored Horses. The Silver coat color is associated with mutations in PMEL17 that resides on ECA6q23. To map the MCOA locus we analyzed 11 genetic markers on ECA6q and herein describe a chromosome interval for the MCOA locus.
Lisa S Andersson - One of the best experts on this subject based on the ideXlab platform.
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Multiple congenital ocular anomalies in Icelandic Horses
BMC Veterinary Research, 2011Co-Authors: Lisa S Andersson, Gabriella Lindgren, Jeanette Axelsson, Richard R. Dubielzig, Björn EkestenAbstract:Background Multiple congenital ocular anomalies (MCOA) syndrome is a hereditary congenital eye defect that was first described in Silver colored Rocky Mountain Horses. The mutation causing this disease is located within a defined chromosomal interval, which also contains the gene and mutation that is associated with the Silver coat color ( PMEL17 , exon 11). Horses that are homozygous for the disease-causing allele have multiple defects (MCOA-phenotype), whilst the heterozygous Horses predominantly have cysts of the iris, ciliary body or retina (Cyst-phenotype). It has been argued that these ocular defects are caused by a recent mutation that is restricted to Horses that are related to the Rocky Mountain Horse breed. For that reason we have examined another Horse breed, the Icelandic Horse, which is historically quite divergent from Rocky Mountain Horses. Results We examined 24 Icelandic Horses and established that the MCOA syndrome is present in this breed. Four of these Horses were categorised as having the MCOA-phenotype and were genotyped as being homozygous for the PMEL17 mutation. The most common clinical signs included megaloglobus, iris stromal hypoplasia, abnormal pectinate ligaments, iridociliary cysts occasionally extending into the peripheral retina and cataracts. The cysts and pectinate ligament abnormalities were observed in the temporal quadrant of the eyes. Fourteen Horses were heterozygous for the PMEL17 mutation and were characterized as having the Cyst-phenotype with cysts and occasionally curvilinear streaks in the peripheral retina. Three additional Horses were genotyped as PMEL17 heterozygotes, but in these Horses we were unable to detect cysts or other forms of anomalies. One eye of a severely vision-impaired 18 month-old stallion, homozygous for the PMEL17 mutation was examined by light microscopy. Redundant duplication of non-pigmented ciliary body epithelium, sometimes forming cysts bulging into the posterior chamber and localized areas of atrophy in the peripheral retina were seen. Conclusions The MCOA syndrome is segregating with the PMEL17 mutation in the Icelandic Horse population. This needs to be taken into consideration in breeding decisions and highlights the fact that MCOA syndrome is present in a breed that are more ancient and not closely related to the Rocky Mountain Horse breed.
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Multiple congenital ocular anomalies in Icelandic Horses
BMC Veterinary Research, 2011Co-Authors: Lisa S Andersson, Gabriella Lindgren, Jeanette Axelsson, Richard R. Dubielzig, Björn EkestenAbstract:Background Multiple congenital ocular anomalies (MCOA) syndrome is a hereditary congenital eye defect that was first described in Silver colored Rocky Mountain Horses. The mutation causing this disease is located within a defined chromosomal interval, which also contains the gene and mutation that is associated with the Silver coat color (PMEL17, exon 11). Horses that are homozygous for the disease-causing allele have multiple defects (MCOA-phenotype), whilst the heterozygous Horses predominantly have cysts of the iris, ciliary body or retina (Cyst-phenotype). It has been argued that these ocular defects are caused by a recent mutation that is restricted to Horses that are related to the Rocky Mountain Horse breed. For that reason we have examined another Horse breed, the Icelandic Horse, which is historically quite divergent from Rocky Mountain Horses.
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Targeted analysis of four breeds narrows equine Multiple Congenital Ocular Anomalies locus to 208 kilobases
Mammalian Genome, 2011Co-Authors: Lisa S Andersson, Rytis Juras, David T Ramsey, Susan Ewart, Gus Cothran, Björn Ekesten, Katarina Lyberg, Sofia Mikko, Gabriella LindgrenAbstract:The syndrome Multiple Congenital Ocular Anomalies (MCOA) is the collective name ascribed to heritable congenital eye defects in Horses. Individuals homozygous for the disease allele (MCOA phenotype) have a wide range of eye anomalies, while heterozygous Horses (Cyst phenotype) predominantly have cysts that originate from the temporal ciliary body, iris, and/or peripheral retina. MCOA syndrome is highly prevalent in the Rocky Mountain Horse but the disease is not limited to this breed. Affected Horses most often have a Silver coat color; however, a pleiotropic link between these phenotypes is yet to be proven. Locating and possibly isolating these traits would provide invaluable knowledge to scientists and breeders. This would favor maintenance of a desirable coat color while addressing the health concerns of the affected breeds, and would also provide insight into the genetic basis of the disease. Identical-by-descent mapping was used to narrow the previous 4.6-Mb region to a 264-kb interval for the MCOA locus. One haplotype common to four breeds showed complete association to the disease (Cyst phenotype, n = 246; MCOA phenotype, n = 83). Candidate genes from the interval, SMARCC2 and IKZF4 , were screened for polymorphisms and genotyped, and segregation analysis allowed the MCOA syndrome region to be shortened to 208 kb. This interval also harbors PMEL17 , the gene causative for Silver coat color. However, by shortening the MCOA locus by a factor of 20, 176 other genes have been unlinked from the disease and only 15 genes remain.
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Equine Multiple Congenital Ocular Anomalies maps to a 4.9 megabase interval on Horse chromosome 6
BMC Genetics, 2008Co-Authors: Lisa S Andersson, Rytis Juras, David T Ramsey, Jessica Eason-butler, Susan Ewart, Gus Cothran, Gabriella LindgrenAbstract:Background Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome consists of a diverse set of abnormalities predominantly localized to the frontal part of the eye. The disease is in agreement with a codominant mode of inheritance in our Horse material. Animals presumed to be heterozygous for the mutant allele have cysts originating from the temporal ciliary body, peripheral retina and/or iris. In contrast, animals predicted to be homozygous for the disease-causing allele possess a wide range of multiple abnormalities, including iridociliary and/or peripheral retinal cysts, iridocorneal angle abnormalities, cornea globosa, iris hypoplasia and congenital cataracts. MCOA is most common in the Rocky Mountain Horse breed where it occurs at a high frequency among Silver colored Horses. The Silver coat color is associated with mutations in PMEL17 that resides on ECA6q23. To map the MCOA locus we analyzed 11 genetic markers on ECA6q and herein describe a chromosome interval for the MCOA locus. Results We performed linkage analysis within 17 paternal half-sib families of the Rocky Mountain Horse breed. More than half of the 131 offspring had the Cyst phenotype and about one third had MCOA. Segregation data were obtained by genotyping 10 microsatellite markers most of which are positioned on ECA6q22-23, as well as the missense mutation for the Silver phenotype in PMEL17 . Significant linkage was found between the MCOA locus and eight of the genetic markers, where marker UPP5 (Theta = 0, z = 12.3), PMEL17ex11 (Theta = 0, z = 19.0) and UPP6 (Theta = 0, z = 17.5) showed complete linkage with the MCOA locus. DNA sequencing of PMEL17 in affected and healthy control individuals did not reveal any additional mutations than the two mutations associated with the Silver coat color. Conclusion The MCOA locus can with high confidence be positioned within a 4.9 megabase (Mb) interval on ECA6q. The genotype data on UPP5 , PMEL17ex11 and UPP6 strongly support the hypothesis that Horses with the Cyst phenotype are heterozygous for the mutant allele and that Horses with the MCOA phenotype are homozygous for the mutant allele.
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Equine Multiple Congenital Ocular Anomalies maps to a 4.9 megabase interval on Horse chromosome 6
BMC Genetics, 2008Co-Authors: Lisa S Andersson, Rytis Juras, David T Ramsey, Jessica Eason-butler, Susan Ewart, Gus Cothran, Gabriella LindgrenAbstract:Background Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome consists of a diverse set of abnormalities predominantly localized to the frontal part of the eye. The disease is in agreement with a codominant mode of inheritance in our Horse material. Animals presumed to be heterozygous for the mutant allele have cysts originating from the temporal ciliary body, peripheral retina and/or iris. In contrast, animals predicted to be homozygous for the disease-causing allele possess a wide range of multiple abnormalities, including iridociliary and/or peripheral retinal cysts, iridocorneal angle abnormalities, cornea globosa, iris hypoplasia and congenital cataracts. MCOA is most common in the Rocky Mountain Horse breed where it occurs at a high frequency among Silver colored Horses. The Silver coat color is associated with mutations in PMEL17 that resides on ECA6q23. To map the MCOA locus we analyzed 11 genetic markers on ECA6q and herein describe a chromosome interval for the MCOA locus.
Rytis Juras - One of the best experts on this subject based on the ideXlab platform.
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Targeted analysis of four breeds narrows equine Multiple Congenital Ocular Anomalies locus to 208 kilobases
Mammalian Genome, 2011Co-Authors: Lisa S Andersson, Rytis Juras, David T Ramsey, Susan Ewart, Gus Cothran, Björn Ekesten, Katarina Lyberg, Sofia Mikko, Gabriella LindgrenAbstract:The syndrome Multiple Congenital Ocular Anomalies (MCOA) is the collective name ascribed to heritable congenital eye defects in Horses. Individuals homozygous for the disease allele (MCOA phenotype) have a wide range of eye anomalies, while heterozygous Horses (Cyst phenotype) predominantly have cysts that originate from the temporal ciliary body, iris, and/or peripheral retina. MCOA syndrome is highly prevalent in the Rocky Mountain Horse but the disease is not limited to this breed. Affected Horses most often have a Silver coat color; however, a pleiotropic link between these phenotypes is yet to be proven. Locating and possibly isolating these traits would provide invaluable knowledge to scientists and breeders. This would favor maintenance of a desirable coat color while addressing the health concerns of the affected breeds, and would also provide insight into the genetic basis of the disease. Identical-by-descent mapping was used to narrow the previous 4.6-Mb region to a 264-kb interval for the MCOA locus. One haplotype common to four breeds showed complete association to the disease (Cyst phenotype, n = 246; MCOA phenotype, n = 83). Candidate genes from the interval, SMARCC2 and IKZF4 , were screened for polymorphisms and genotyped, and segregation analysis allowed the MCOA syndrome region to be shortened to 208 kb. This interval also harbors PMEL17 , the gene causative for Silver coat color. However, by shortening the MCOA locus by a factor of 20, 176 other genes have been unlinked from the disease and only 15 genes remain.
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Equine Multiple Congenital Ocular Anomalies maps to a 4.9 megabase interval on Horse chromosome 6
BMC Genetics, 2008Co-Authors: Lisa S Andersson, Rytis Juras, David T Ramsey, Jessica Eason-butler, Susan Ewart, Gus Cothran, Gabriella LindgrenAbstract:Background Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome consists of a diverse set of abnormalities predominantly localized to the frontal part of the eye. The disease is in agreement with a codominant mode of inheritance in our Horse material. Animals presumed to be heterozygous for the mutant allele have cysts originating from the temporal ciliary body, peripheral retina and/or iris. In contrast, animals predicted to be homozygous for the disease-causing allele possess a wide range of multiple abnormalities, including iridociliary and/or peripheral retinal cysts, iridocorneal angle abnormalities, cornea globosa, iris hypoplasia and congenital cataracts. MCOA is most common in the Rocky Mountain Horse breed where it occurs at a high frequency among Silver colored Horses. The Silver coat color is associated with mutations in PMEL17 that resides on ECA6q23. To map the MCOA locus we analyzed 11 genetic markers on ECA6q and herein describe a chromosome interval for the MCOA locus. Results We performed linkage analysis within 17 paternal half-sib families of the Rocky Mountain Horse breed. More than half of the 131 offspring had the Cyst phenotype and about one third had MCOA. Segregation data were obtained by genotyping 10 microsatellite markers most of which are positioned on ECA6q22-23, as well as the missense mutation for the Silver phenotype in PMEL17 . Significant linkage was found between the MCOA locus and eight of the genetic markers, where marker UPP5 (Theta = 0, z = 12.3), PMEL17ex11 (Theta = 0, z = 19.0) and UPP6 (Theta = 0, z = 17.5) showed complete linkage with the MCOA locus. DNA sequencing of PMEL17 in affected and healthy control individuals did not reveal any additional mutations than the two mutations associated with the Silver coat color. Conclusion The MCOA locus can with high confidence be positioned within a 4.9 megabase (Mb) interval on ECA6q. The genotype data on UPP5 , PMEL17ex11 and UPP6 strongly support the hypothesis that Horses with the Cyst phenotype are heterozygous for the mutant allele and that Horses with the MCOA phenotype are homozygous for the mutant allele.
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Equine Multiple Congenital Ocular Anomalies maps to a 4.9 megabase interval on Horse chromosome 6
BMC Genetics, 2008Co-Authors: Lisa S Andersson, Rytis Juras, David T Ramsey, Jessica Eason-butler, Susan Ewart, Gus Cothran, Gabriella LindgrenAbstract:Background Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome consists of a diverse set of abnormalities predominantly localized to the frontal part of the eye. The disease is in agreement with a codominant mode of inheritance in our Horse material. Animals presumed to be heterozygous for the mutant allele have cysts originating from the temporal ciliary body, peripheral retina and/or iris. In contrast, animals predicted to be homozygous for the disease-causing allele possess a wide range of multiple abnormalities, including iridociliary and/or peripheral retinal cysts, iridocorneal angle abnormalities, cornea globosa, iris hypoplasia and congenital cataracts. MCOA is most common in the Rocky Mountain Horse breed where it occurs at a high frequency among Silver colored Horses. The Silver coat color is associated with mutations in PMEL17 that resides on ECA6q23. To map the MCOA locus we analyzed 11 genetic markers on ECA6q and herein describe a chromosome interval for the MCOA locus.
Gus Cothran - One of the best experts on this subject based on the ideXlab platform.
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Targeted analysis of four breeds narrows equine Multiple Congenital Ocular Anomalies locus to 208 kilobases
Mammalian Genome, 2011Co-Authors: Lisa S Andersson, Rytis Juras, David T Ramsey, Susan Ewart, Gus Cothran, Björn Ekesten, Katarina Lyberg, Sofia Mikko, Gabriella LindgrenAbstract:The syndrome Multiple Congenital Ocular Anomalies (MCOA) is the collective name ascribed to heritable congenital eye defects in Horses. Individuals homozygous for the disease allele (MCOA phenotype) have a wide range of eye anomalies, while heterozygous Horses (Cyst phenotype) predominantly have cysts that originate from the temporal ciliary body, iris, and/or peripheral retina. MCOA syndrome is highly prevalent in the Rocky Mountain Horse but the disease is not limited to this breed. Affected Horses most often have a Silver coat color; however, a pleiotropic link between these phenotypes is yet to be proven. Locating and possibly isolating these traits would provide invaluable knowledge to scientists and breeders. This would favor maintenance of a desirable coat color while addressing the health concerns of the affected breeds, and would also provide insight into the genetic basis of the disease. Identical-by-descent mapping was used to narrow the previous 4.6-Mb region to a 264-kb interval for the MCOA locus. One haplotype common to four breeds showed complete association to the disease (Cyst phenotype, n = 246; MCOA phenotype, n = 83). Candidate genes from the interval, SMARCC2 and IKZF4 , were screened for polymorphisms and genotyped, and segregation analysis allowed the MCOA syndrome region to be shortened to 208 kb. This interval also harbors PMEL17 , the gene causative for Silver coat color. However, by shortening the MCOA locus by a factor of 20, 176 other genes have been unlinked from the disease and only 15 genes remain.
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Equine Multiple Congenital Ocular Anomalies maps to a 4.9 megabase interval on Horse chromosome 6
BMC Genetics, 2008Co-Authors: Lisa S Andersson, Rytis Juras, David T Ramsey, Jessica Eason-butler, Susan Ewart, Gus Cothran, Gabriella LindgrenAbstract:Background Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome consists of a diverse set of abnormalities predominantly localized to the frontal part of the eye. The disease is in agreement with a codominant mode of inheritance in our Horse material. Animals presumed to be heterozygous for the mutant allele have cysts originating from the temporal ciliary body, peripheral retina and/or iris. In contrast, animals predicted to be homozygous for the disease-causing allele possess a wide range of multiple abnormalities, including iridociliary and/or peripheral retinal cysts, iridocorneal angle abnormalities, cornea globosa, iris hypoplasia and congenital cataracts. MCOA is most common in the Rocky Mountain Horse breed where it occurs at a high frequency among Silver colored Horses. The Silver coat color is associated with mutations in PMEL17 that resides on ECA6q23. To map the MCOA locus we analyzed 11 genetic markers on ECA6q and herein describe a chromosome interval for the MCOA locus. Results We performed linkage analysis within 17 paternal half-sib families of the Rocky Mountain Horse breed. More than half of the 131 offspring had the Cyst phenotype and about one third had MCOA. Segregation data were obtained by genotyping 10 microsatellite markers most of which are positioned on ECA6q22-23, as well as the missense mutation for the Silver phenotype in PMEL17 . Significant linkage was found between the MCOA locus and eight of the genetic markers, where marker UPP5 (Theta = 0, z = 12.3), PMEL17ex11 (Theta = 0, z = 19.0) and UPP6 (Theta = 0, z = 17.5) showed complete linkage with the MCOA locus. DNA sequencing of PMEL17 in affected and healthy control individuals did not reveal any additional mutations than the two mutations associated with the Silver coat color. Conclusion The MCOA locus can with high confidence be positioned within a 4.9 megabase (Mb) interval on ECA6q. The genotype data on UPP5 , PMEL17ex11 and UPP6 strongly support the hypothesis that Horses with the Cyst phenotype are heterozygous for the mutant allele and that Horses with the MCOA phenotype are homozygous for the mutant allele.
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Equine Multiple Congenital Ocular Anomalies maps to a 4.9 megabase interval on Horse chromosome 6
BMC Genetics, 2008Co-Authors: Lisa S Andersson, Rytis Juras, David T Ramsey, Jessica Eason-butler, Susan Ewart, Gus Cothran, Gabriella LindgrenAbstract:Background Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome consists of a diverse set of abnormalities predominantly localized to the frontal part of the eye. The disease is in agreement with a codominant mode of inheritance in our Horse material. Animals presumed to be heterozygous for the mutant allele have cysts originating from the temporal ciliary body, peripheral retina and/or iris. In contrast, animals predicted to be homozygous for the disease-causing allele possess a wide range of multiple abnormalities, including iridociliary and/or peripheral retinal cysts, iridocorneal angle abnormalities, cornea globosa, iris hypoplasia and congenital cataracts. MCOA is most common in the Rocky Mountain Horse breed where it occurs at a high frequency among Silver colored Horses. The Silver coat color is associated with mutations in PMEL17 that resides on ECA6q23. To map the MCOA locus we analyzed 11 genetic markers on ECA6q and herein describe a chromosome interval for the MCOA locus.
Susan Ewart - One of the best experts on this subject based on the ideXlab platform.
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Targeted analysis of four breeds narrows equine Multiple Congenital Ocular Anomalies locus to 208 kilobases
Mammalian Genome, 2011Co-Authors: Lisa S Andersson, Rytis Juras, David T Ramsey, Susan Ewart, Gus Cothran, Björn Ekesten, Katarina Lyberg, Sofia Mikko, Gabriella LindgrenAbstract:The syndrome Multiple Congenital Ocular Anomalies (MCOA) is the collective name ascribed to heritable congenital eye defects in Horses. Individuals homozygous for the disease allele (MCOA phenotype) have a wide range of eye anomalies, while heterozygous Horses (Cyst phenotype) predominantly have cysts that originate from the temporal ciliary body, iris, and/or peripheral retina. MCOA syndrome is highly prevalent in the Rocky Mountain Horse but the disease is not limited to this breed. Affected Horses most often have a Silver coat color; however, a pleiotropic link between these phenotypes is yet to be proven. Locating and possibly isolating these traits would provide invaluable knowledge to scientists and breeders. This would favor maintenance of a desirable coat color while addressing the health concerns of the affected breeds, and would also provide insight into the genetic basis of the disease. Identical-by-descent mapping was used to narrow the previous 4.6-Mb region to a 264-kb interval for the MCOA locus. One haplotype common to four breeds showed complete association to the disease (Cyst phenotype, n = 246; MCOA phenotype, n = 83). Candidate genes from the interval, SMARCC2 and IKZF4 , were screened for polymorphisms and genotyped, and segregation analysis allowed the MCOA syndrome region to be shortened to 208 kb. This interval also harbors PMEL17 , the gene causative for Silver coat color. However, by shortening the MCOA locus by a factor of 20, 176 other genes have been unlinked from the disease and only 15 genes remain.
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Equine Multiple Congenital Ocular Anomalies maps to a 4.9 megabase interval on Horse chromosome 6
BMC Genetics, 2008Co-Authors: Lisa S Andersson, Rytis Juras, David T Ramsey, Jessica Eason-butler, Susan Ewart, Gus Cothran, Gabriella LindgrenAbstract:Background Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome consists of a diverse set of abnormalities predominantly localized to the frontal part of the eye. The disease is in agreement with a codominant mode of inheritance in our Horse material. Animals presumed to be heterozygous for the mutant allele have cysts originating from the temporal ciliary body, peripheral retina and/or iris. In contrast, animals predicted to be homozygous for the disease-causing allele possess a wide range of multiple abnormalities, including iridociliary and/or peripheral retinal cysts, iridocorneal angle abnormalities, cornea globosa, iris hypoplasia and congenital cataracts. MCOA is most common in the Rocky Mountain Horse breed where it occurs at a high frequency among Silver colored Horses. The Silver coat color is associated with mutations in PMEL17 that resides on ECA6q23. To map the MCOA locus we analyzed 11 genetic markers on ECA6q and herein describe a chromosome interval for the MCOA locus. Results We performed linkage analysis within 17 paternal half-sib families of the Rocky Mountain Horse breed. More than half of the 131 offspring had the Cyst phenotype and about one third had MCOA. Segregation data were obtained by genotyping 10 microsatellite markers most of which are positioned on ECA6q22-23, as well as the missense mutation for the Silver phenotype in PMEL17 . Significant linkage was found between the MCOA locus and eight of the genetic markers, where marker UPP5 (Theta = 0, z = 12.3), PMEL17ex11 (Theta = 0, z = 19.0) and UPP6 (Theta = 0, z = 17.5) showed complete linkage with the MCOA locus. DNA sequencing of PMEL17 in affected and healthy control individuals did not reveal any additional mutations than the two mutations associated with the Silver coat color. Conclusion The MCOA locus can with high confidence be positioned within a 4.9 megabase (Mb) interval on ECA6q. The genotype data on UPP5 , PMEL17ex11 and UPP6 strongly support the hypothesis that Horses with the Cyst phenotype are heterozygous for the mutant allele and that Horses with the MCOA phenotype are homozygous for the mutant allele.
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Equine Multiple Congenital Ocular Anomalies maps to a 4.9 megabase interval on Horse chromosome 6
BMC Genetics, 2008Co-Authors: Lisa S Andersson, Rytis Juras, David T Ramsey, Jessica Eason-butler, Susan Ewart, Gus Cothran, Gabriella LindgrenAbstract:Background Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome consists of a diverse set of abnormalities predominantly localized to the frontal part of the eye. The disease is in agreement with a codominant mode of inheritance in our Horse material. Animals presumed to be heterozygous for the mutant allele have cysts originating from the temporal ciliary body, peripheral retina and/or iris. In contrast, animals predicted to be homozygous for the disease-causing allele possess a wide range of multiple abnormalities, including iridociliary and/or peripheral retinal cysts, iridocorneal angle abnormalities, cornea globosa, iris hypoplasia and congenital cataracts. MCOA is most common in the Rocky Mountain Horse breed where it occurs at a high frequency among Silver colored Horses. The Silver coat color is associated with mutations in PMEL17 that resides on ECA6q23. To map the MCOA locus we analyzed 11 genetic markers on ECA6q and herein describe a chromosome interval for the MCOA locus.
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The Horse homolog of congenital aniridia conforms to codominant inheritance
Journal of Heredity, 2000Co-Authors: Susan Ewart, Dt Ramsey, J Xu, D MeyersAbstract:: Anterior segment dysgenesis syndrome occurs frequently in Rocky Mountain Horses and has two distinct ocular phenotypes: (1) large cysts originating from the temporal ciliary body or peripheral retina and (2) multiple anterior segment anomalies including ciliary cysts, iris hypoplasia, iridocorneal adhesions and opacification, nuclear cataract, and megalocornea. To determine if anterior segment dysgenesis syndrome is heritable in Horses we performed ophthalmic examinations and collected pedigree information on Horses (n = 516) in an extended Rocky Mountain Horse pedigree. Logistic regressive segregation analysis of a subset of animals (n = 337) in which the ocular phenotypes of progeny and both parents were known indicated that the codominant inheritance model best fit the data. This model predicted cyst phenotype expression in heterozygous animals and multiple anterior segment anomalies in homozygous animals. Several cases of nonpenetrance of the cyst phenotype were detected in one lineage. The close resemblance between the inheritance and lesions observed in Small eye mice and rats, humans with congenital aniridia or anterior segment malformation, and Horses with anterior segment dysgenesis syndrome supported the conclusion that anterior segment dysgenesis syndrome in the Horse may be homologous to similar ophthalmic anomalies in other species.
