The Experts below are selected from a list of 1923 Experts worldwide ranked by ideXlab platform
Angela M Christiano - One of the best experts on this subject based on the ideXlab platform.
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autosomal dominant woolly Hair resulting from disruption of keratin 74 krt74 a potential determinant of human Hair Texture
American Journal of Human Genetics, 2010Co-Authors: Yutaka Shimomura, Muhammad Wajid, Lynn Petukhova, Mazen Kurban, Angela M ChristianoAbstract:Autosomal-dominant woolly Hair (ADWH) is a rare disorder characterized by tightly curled Hair. The molecular basis of ADWH has not previously been reported. In this study, we identified a Pakistani family with ADWH. The family showed linkage to chromosome 12q12-q14.1, containing the type II keratin gene cluster. We discovered a heterozygous mutation, p.Asn148Lys, within the helix initiation motif of the keratin 74 (KRT74) gene in all affected family members. KRT74 encodes the inner root sheath (IRS)-specific epithelial (soft) keratin 74. We demonstrate that the mutant K74 protein results in disruption of keratin intermediate filament formation in cultured cells, most likely in a dominant-negative manner. Furthermore, we sequenced the mouse Krt71-74 genes in the dominant Caracul-like 4 (Cal4) allele, which is characterized by a wavy-coat phenotype and maps to the same region of mouse chromosome 15 as the Caracul (Ca) and Reduced coat (Rco) alleles. We identified a heterozygous mutation, p.Glu440Lys, not in Krt74 but in the neighboring gene, Krt71. Krt71 was previously reported to harbor Ca and Rco mutations, as well as a coding SNP that is associated with curly-coated dogs. In this study, we define the ADWH phenotype resulting from a mutation in a Hair-follicle-specific epithelial keratin in humans. Our findings not only further underscore the crucial roles of the IRS-specific epithelial keratin genes Krt71-74 in Hair disorders but also open the possibility that these genes might function as genetic determinants of normal variation in Hair Texture across mammalian species.
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disruption of p2ry5 an orphan g protein coupled receptor underlies autosomal recessive woolly Hair
Nature Genetics, 2008Co-Authors: Yutaka Shimomura, Muhammad Wajid, Yoshiyuki Ishii, Lawrence Shapiro, Lynn Petukhova, Derek Gordon, Angela M ChristianoAbstract:The genetic determinants of Hair Texture in humans are largely unknown. Several human syndromes exist in which woolly Hair comprises a part of the phenotype; however, simple autosomal recessive inheritance of isolated woolly Hair has only rarely been reported1,2. To identify a gene involved in controlling Hair Texture, we performed genetic linkage analysis in six families of Pakistani origin with autosomal recessive woolly Hair (ARWH; OMIM 278150). All six families showed linkage to chromosome 13q14.2–14.3 (Z = 17.97). In all cases, we discovered pathogenic mutations in P2RY5, which encodes a G protein–coupled receptor and is a nested gene residing within intron 17 of the retinoblastoma 1 (RB1) gene. P2RY5 is expressed in both Henle's and Huxley's layers of the inner root sheath of the Hair follicle. Our findings indicate that disruption of P2RY5 underlies ARWH and, more broadly, uncover a new gene involved in determining Hair Texture in humans.
Yutaka Shimomura - One of the best experts on this subject based on the ideXlab platform.
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autosomal dominant woolly Hair resulting from disruption of keratin 74 krt74 a potential determinant of human Hair Texture
American Journal of Human Genetics, 2010Co-Authors: Yutaka Shimomura, Muhammad Wajid, Lynn Petukhova, Mazen Kurban, Angela M ChristianoAbstract:Autosomal-dominant woolly Hair (ADWH) is a rare disorder characterized by tightly curled Hair. The molecular basis of ADWH has not previously been reported. In this study, we identified a Pakistani family with ADWH. The family showed linkage to chromosome 12q12-q14.1, containing the type II keratin gene cluster. We discovered a heterozygous mutation, p.Asn148Lys, within the helix initiation motif of the keratin 74 (KRT74) gene in all affected family members. KRT74 encodes the inner root sheath (IRS)-specific epithelial (soft) keratin 74. We demonstrate that the mutant K74 protein results in disruption of keratin intermediate filament formation in cultured cells, most likely in a dominant-negative manner. Furthermore, we sequenced the mouse Krt71-74 genes in the dominant Caracul-like 4 (Cal4) allele, which is characterized by a wavy-coat phenotype and maps to the same region of mouse chromosome 15 as the Caracul (Ca) and Reduced coat (Rco) alleles. We identified a heterozygous mutation, p.Glu440Lys, not in Krt74 but in the neighboring gene, Krt71. Krt71 was previously reported to harbor Ca and Rco mutations, as well as a coding SNP that is associated with curly-coated dogs. In this study, we define the ADWH phenotype resulting from a mutation in a Hair-follicle-specific epithelial keratin in humans. Our findings not only further underscore the crucial roles of the IRS-specific epithelial keratin genes Krt71-74 in Hair disorders but also open the possibility that these genes might function as genetic determinants of normal variation in Hair Texture across mammalian species.
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disruption of p2ry5 an orphan g protein coupled receptor underlies autosomal recessive woolly Hair
Nature Genetics, 2008Co-Authors: Yutaka Shimomura, Muhammad Wajid, Yoshiyuki Ishii, Lawrence Shapiro, Lynn Petukhova, Derek Gordon, Angela M ChristianoAbstract:The genetic determinants of Hair Texture in humans are largely unknown. Several human syndromes exist in which woolly Hair comprises a part of the phenotype; however, simple autosomal recessive inheritance of isolated woolly Hair has only rarely been reported1,2. To identify a gene involved in controlling Hair Texture, we performed genetic linkage analysis in six families of Pakistani origin with autosomal recessive woolly Hair (ARWH; OMIM 278150). All six families showed linkage to chromosome 13q14.2–14.3 (Z = 17.97). In all cases, we discovered pathogenic mutations in P2RY5, which encodes a G protein–coupled receptor and is a nested gene residing within intron 17 of the retinoblastoma 1 (RB1) gene. P2RY5 is expressed in both Henle's and Huxley's layers of the inner root sheath of the Hair follicle. Our findings indicate that disruption of P2RY5 underlies ARWH and, more broadly, uncover a new gene involved in determining Hair Texture in humans.
Muhammad Wajid - One of the best experts on this subject based on the ideXlab platform.
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autosomal dominant woolly Hair resulting from disruption of keratin 74 krt74 a potential determinant of human Hair Texture
American Journal of Human Genetics, 2010Co-Authors: Yutaka Shimomura, Muhammad Wajid, Lynn Petukhova, Mazen Kurban, Angela M ChristianoAbstract:Autosomal-dominant woolly Hair (ADWH) is a rare disorder characterized by tightly curled Hair. The molecular basis of ADWH has not previously been reported. In this study, we identified a Pakistani family with ADWH. The family showed linkage to chromosome 12q12-q14.1, containing the type II keratin gene cluster. We discovered a heterozygous mutation, p.Asn148Lys, within the helix initiation motif of the keratin 74 (KRT74) gene in all affected family members. KRT74 encodes the inner root sheath (IRS)-specific epithelial (soft) keratin 74. We demonstrate that the mutant K74 protein results in disruption of keratin intermediate filament formation in cultured cells, most likely in a dominant-negative manner. Furthermore, we sequenced the mouse Krt71-74 genes in the dominant Caracul-like 4 (Cal4) allele, which is characterized by a wavy-coat phenotype and maps to the same region of mouse chromosome 15 as the Caracul (Ca) and Reduced coat (Rco) alleles. We identified a heterozygous mutation, p.Glu440Lys, not in Krt74 but in the neighboring gene, Krt71. Krt71 was previously reported to harbor Ca and Rco mutations, as well as a coding SNP that is associated with curly-coated dogs. In this study, we define the ADWH phenotype resulting from a mutation in a Hair-follicle-specific epithelial keratin in humans. Our findings not only further underscore the crucial roles of the IRS-specific epithelial keratin genes Krt71-74 in Hair disorders but also open the possibility that these genes might function as genetic determinants of normal variation in Hair Texture across mammalian species.
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disruption of p2ry5 an orphan g protein coupled receptor underlies autosomal recessive woolly Hair
Nature Genetics, 2008Co-Authors: Yutaka Shimomura, Muhammad Wajid, Yoshiyuki Ishii, Lawrence Shapiro, Lynn Petukhova, Derek Gordon, Angela M ChristianoAbstract:The genetic determinants of Hair Texture in humans are largely unknown. Several human syndromes exist in which woolly Hair comprises a part of the phenotype; however, simple autosomal recessive inheritance of isolated woolly Hair has only rarely been reported1,2. To identify a gene involved in controlling Hair Texture, we performed genetic linkage analysis in six families of Pakistani origin with autosomal recessive woolly Hair (ARWH; OMIM 278150). All six families showed linkage to chromosome 13q14.2–14.3 (Z = 17.97). In all cases, we discovered pathogenic mutations in P2RY5, which encodes a G protein–coupled receptor and is a nested gene residing within intron 17 of the retinoblastoma 1 (RB1) gene. P2RY5 is expressed in both Henle's and Huxley's layers of the inner root sheath of the Hair follicle. Our findings indicate that disruption of P2RY5 underlies ARWH and, more broadly, uncover a new gene involved in determining Hair Texture in humans.
Lynn Petukhova - One of the best experts on this subject based on the ideXlab platform.
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autosomal dominant woolly Hair resulting from disruption of keratin 74 krt74 a potential determinant of human Hair Texture
American Journal of Human Genetics, 2010Co-Authors: Yutaka Shimomura, Muhammad Wajid, Lynn Petukhova, Mazen Kurban, Angela M ChristianoAbstract:Autosomal-dominant woolly Hair (ADWH) is a rare disorder characterized by tightly curled Hair. The molecular basis of ADWH has not previously been reported. In this study, we identified a Pakistani family with ADWH. The family showed linkage to chromosome 12q12-q14.1, containing the type II keratin gene cluster. We discovered a heterozygous mutation, p.Asn148Lys, within the helix initiation motif of the keratin 74 (KRT74) gene in all affected family members. KRT74 encodes the inner root sheath (IRS)-specific epithelial (soft) keratin 74. We demonstrate that the mutant K74 protein results in disruption of keratin intermediate filament formation in cultured cells, most likely in a dominant-negative manner. Furthermore, we sequenced the mouse Krt71-74 genes in the dominant Caracul-like 4 (Cal4) allele, which is characterized by a wavy-coat phenotype and maps to the same region of mouse chromosome 15 as the Caracul (Ca) and Reduced coat (Rco) alleles. We identified a heterozygous mutation, p.Glu440Lys, not in Krt74 but in the neighboring gene, Krt71. Krt71 was previously reported to harbor Ca and Rco mutations, as well as a coding SNP that is associated with curly-coated dogs. In this study, we define the ADWH phenotype resulting from a mutation in a Hair-follicle-specific epithelial keratin in humans. Our findings not only further underscore the crucial roles of the IRS-specific epithelial keratin genes Krt71-74 in Hair disorders but also open the possibility that these genes might function as genetic determinants of normal variation in Hair Texture across mammalian species.
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disruption of p2ry5 an orphan g protein coupled receptor underlies autosomal recessive woolly Hair
Nature Genetics, 2008Co-Authors: Yutaka Shimomura, Muhammad Wajid, Yoshiyuki Ishii, Lawrence Shapiro, Lynn Petukhova, Derek Gordon, Angela M ChristianoAbstract:The genetic determinants of Hair Texture in humans are largely unknown. Several human syndromes exist in which woolly Hair comprises a part of the phenotype; however, simple autosomal recessive inheritance of isolated woolly Hair has only rarely been reported1,2. To identify a gene involved in controlling Hair Texture, we performed genetic linkage analysis in six families of Pakistani origin with autosomal recessive woolly Hair (ARWH; OMIM 278150). All six families showed linkage to chromosome 13q14.2–14.3 (Z = 17.97). In all cases, we discovered pathogenic mutations in P2RY5, which encodes a G protein–coupled receptor and is a nested gene residing within intron 17 of the retinoblastoma 1 (RB1) gene. P2RY5 is expressed in both Henle's and Huxley's layers of the inner root sheath of the Hair follicle. Our findings indicate that disruption of P2RY5 underlies ARWH and, more broadly, uncover a new gene involved in determining Hair Texture in humans.
Muhammad Ansar - One of the best experts on this subject based on the ideXlab platform.
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a homozygous missense variant in type i keratin krt25 causes autosomal recessive woolly Hair
Journal of Medical Genetics, 2015Co-Authors: Muhammad Ansar, Syed Irfan Raza, Shamim Shahi, Anushree Acharya, Joshua D Smith, Jay Shendure, Michael J Bamshad, Deborah A NickersonAbstract:Background Woolly Hair (WH) is a Hair abnormality that is primarily characterised by tightly curled Hair with abnormal growth. Methods In two unrelated consanguineous Pakistani families with non-syndromic autosomal recessive (AR) WH, homozygosity mapping and linkage analysis identified a locus within 17q21.1–q22, which contains the type I keratin gene cluster. A DNA sample from an affected individual from each family underwent exome sequencing. Results A homozygous missense variant c.950T>C (p.(Leu317Pro)) within KRT25 segregated with ARWH in both families, and has a combined maximum two-point LOD score of 7.9 at ϴ=0. The KRT25 variant is predicted to result in disruption of the second α-helical rod domain and the entire protein structure, thus possibly interfering with heterodimerisation of K25 with type II keratins within the inner root sheath (IRS) of the Hair follicle and the medulla of the Hair shaft. Conclusions Our findings implicate a novel gene involved in human Hair abnormality, and are consistent with the curled, fragile Hair found in mice with Krt25 mutations, and further support the role of IRS-specific type I keratins in Hair follicle development and maintenance of Hair Texture.
