Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 76
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Anim Sci ; 98(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31863114

RESUMO

The keratin-associated proteins (KAPs) are structural components of wool fibers and variation in the genes encoding the KAPs can affect wool traits. In this study, sequence variation in the ovine KAP7-1 gene (KRTAP7-1) was investigated in 222 sheep across 5 different Pakistani breeds and breed crosses. Two previously identified variants (A and B) of the KRTAP7-1 coding sequence were identified. The frequency of the genotypes AA and AB was 76% and 23%, respectively, and that of BB was 1%. The association of sequence variation with various wool traits and measurements included yield (the proportion of greasy fleece weight that is clean fleece), mean staple length (MSL), wool bulk, mean fiber diameter, fiber diameter SD, the coefficient of variation of fiber diameter, medullation, the SD of medullation, the coefficient of variation of medullation, fiber opacity, the SD of opacity, and the coefficient of variation of opacity. Variation in KRTAP7-1 was found to be associated with yield (P = 0.017). The adjusted mean yield of sheep of genotype AA (n = 169) was 79.9 ±â€…2.72%, while that of genotype AB (n = 51) was 81.9 ±â€…3.37%. There was also an association between variation in KRTAP7-1 and MSL (P = 0.024), with sheep of genotype AA (n = 169) having an adjusted mean MSL of 47.3 ±â€…0.57 mm compared with sheep of genotype AB (n = 51, 50.9 ±â€…0.65 mm). Yield and MSL are both important wool production traits, hence variation in KRTAP7-1 needs to be further investigated in more sheep of differing breed.


Assuntos
Queratinas Específicas do Cabelo/genética , Polimorfismo Genético , Ovinos/genética , Lã/crescimento & desenvolvimento , Animais , Peso Corporal/genética , Cruzamento , Genótipo , Queratinas/genética , Fenótipo
2.
Genes (Basel) ; 10(7)2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31261764

RESUMO

Intensive artificial and natural selection have shaped substantial variation among European horse breeds. Whereas most equine selection signature studies employ divergent genetic population structures in order to derive specific inter-breed targets of selection, we screened a total of 1476 horses originating from 12 breeds for the loss of genetic diversity by runs of homozygosity (ROH) utilizing a 670,000 single nucleotide polymorphism (SNP) genotyping array. Overlapping homozygous regions (ROH islands) indicating signatures of selection were identified by breed and similarities/dissimilarities between populations were evaluated. In the entire dataset, 180 ROH islands were identified, whilst 100 islands were breed specific, all other overlapped in 36 genomic regions with at least one ROH island of another breed. Furthermore, two ROH hot spots were determined at horse chromosome 3 (ECA3) and ECA11. Besides the confirmation of previously documented target genes involved in selection for coat color (MC1R, STX17, ASIP), body size (LCORL/NCAPG, ZFAT, LASP1, HMGA2), racing ability (PPARGC1A), behavioral traits (GRIN2B, NTM/OPCML) and gait patterns (DMRT3), several putative target genes related to embryonic morphogenesis (HOXB), energy metabolism (IGFBP-1, IGFBP-3), hair follicle morphogenesis (KRT25, KRT27, INTU) and autophagy (RALB) were highlighted. Furthermore, genes were pinpointed which might be involved in environmental adaptation of specific habitats (UVSSA, STXBP4, COX11, HLF, MMD).


Assuntos
Cruzamento , Homozigoto , Cavalos/genética , Proteína Agouti Sinalizadora/genética , Animais , Fatores de Transcrição de Zíper de Leucina Básica/genética , Proteínas de Transporte/genética , Moléculas de Adesão Celular/genética , Proteínas do Citoesqueleto/genética , Ontologia Genética , Genoma , Proteína HMGA2/genética , Proteínas de Homeodomínio/genética , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Queratinas Específicas do Cabelo/genética , Proteínas de Membrana/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Polimorfismo de Nucleotídeo Único , Proteínas Repressoras/genética , Fatores de Transcrição/genética , Proteínas de Transporte Vesicular/genética , Proteínas ral de Ligação ao GTP/genética
3.
J Drugs Dermatol ; 18(3): 246-250, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30909328

RESUMO

The purpose of this review is to discuss the disease process and wide variety of treatment options for psuedofolliculitis barbae (PFB), or razor bumps. PFB is caused by hair follicles penetrating the skin and causing an inflammatory response. PFB can occur to anyone who shaves, and is more likely in those with curly hair. PFB can cause significant hyperpigmentation and scarring, more noticeable in darker skin types. PFB can be treated with a variety of topical, systemic, or light/laser therapies. Minimal progress has been made in treating PFB in recent years, partially due to the success of well-established current treatments discussed in this review. The most effective treatments involve a multifaceted approach including behavioral changes in shaving habits as well as the use of topical therapies. J Drugs Dermatol. 2019;18(3):246-250.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Doenças do Cabelo/terapia , Remoção de Cabelo/efeitos adversos , Terapia com Luz de Baixa Intensidade/métodos , Fotoquimioterapia/métodos , Administração Cutânea , Administração Oral , Antibacterianos/uso terapêutico , Face , Hábitos , Doenças do Cabelo/epidemiologia , Doenças do Cabelo/etiologia , Folículo Piloso/patologia , Folículo Piloso/efeitos da radiação , Humanos , Queratinas Específicas do Cabelo/genética , Queratinas Tipo II/genética , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
4.
Anim Genet ; 50(1): 97-100, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30444027

RESUMO

Major characteristics of coat variation in dogs can be explained by variants in only a few genes. Until now, only one missense variant in the KRT71 gene, p.Arg151Trp, has been reported to cause curly hair in dogs. However, this variant does not explain the curly coat in all breeds as the mutant 151 Trp allele, for example, is absent in Curly Coated Retrievers. We sequenced the genome of a Curly Coated Retriever at 22× coverage and searched for variants in the KRT71 gene. Only one protein-changing variant was present in a homozygous state in the Curly Coated Retriever and absent or present in a heterozygous state in 221 control dogs from different dog breeds. This variant, NM_001197029.1:c.1266_1273delinsACA, was an indel variant in exon 7 that caused a frameshift and an altered and probably extended C-terminus of the KRT71 protein NP_001183958.1:p.(Ser422ArgfsTer?). Using Sanger sequencing, we found that the variant was fixed in a cohort of 125 Curly Coated Retrievers and segregating in five of 14 additionally tested breeds with a curly or wavy coat. KRT71 variants cause curly hair in humans, mice, rats, cats and dogs. Specific KRT71 variants were further shown to cause alopecia. Based on this knowledge from other species and the predicted molecular consequence of the newly identified canine KRT71 variant, it is a compelling candidate causing a second curly hair allele in dogs. It might cause a slightly different coat phenotype than the previously published p.Arg151Trp variant and could potentially be associated with follicular dysplasia in dogs.


Assuntos
Cães/genética , Cabelo , Queratinas Específicas do Cabelo/genética , Alelos , Animais , Cruzamento , Heterozigoto , Homozigoto , Mutação INDEL , Fenótipo
5.
Anim Genet ; 50(1): 101-104, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30456859

RESUMO

Curly fur is a common phenotype in many dog breeds, known to result from a missense variant (c.451C>T) in exon 2 of the keratin 71 (KRT71) gene. During screening for this variant across various breeds, we found that Curly Coated Retrievers (CCRs) fixed with the trait did not carry the known variant. By analysis of whole-genome sequencing data of one CCR we identified a novel genetic cause for curly fur. We found a novel structural variant in exon 7 of the KRT71 gene (c.1266_1273delinsACA) that was predicted to result in a frameshift and stop loss, therefore significantly affecting the structure of the protein, if translated. The variant was also found at lower frequencies in five other breeds, including Lagotto Romagnolo, Bichon Frise, Spanish Water Dog, Chesapeake Bay Retriever and Irish Terrier. One curly-coated Lagotto carried neither of the two KRT71 variants. These results identify a second variant for curly coat in KRT71 and suggest the existence of additional alleles. This study enables the development of an additional KRT71 gene test for breeders to understand and manage coat types.


Assuntos
Cães/genética , Cabelo , Queratinas Específicas do Cabelo/genética , Animais , Cruzamento , Éxons , Mutação da Fase de Leitura , Fenótipo
6.
Sci Rep ; 8(1): 6374, 2018 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-29686323

RESUMO

Curly coat represents an extraordinary type of coat in horses, particularly seen in American Bashkir Curly Horses and Missouri Foxtrotters. In some horses with curly coat, a hypotrichosis of variable extent was observed, making the phenotype appear more complex. In our study, we aimed at investigating the genetic background of curly coat with and without hypotrichosis using high density bead chip genotype and next generation sequencing data. Genome-wide association analysis detected significant signals (p = 1.412 × 10-05-1.102 × 10-08) on horse chromosome 11 at 22-35 Mb. In this significantly associated region, six missense variants were filtered out from whole-genome sequencing data of three curly coated horses of which two variants within KRT25 and SP6 could explain all hair phenotypes. Horses heterozygous or homozygous only for KRT25 variant showed curly coat and hypotrichosis, whereas horses with SP6 variant only, exhibited curly coat without hypotrichosis. Horses with mutant alleles in both variants developed curly hair and hypotrichosis. Thus, mutant KRT25 allele is masking SP6 allele effect, indicative for epistasis of KRT25 variant over SP6 variant. In summary, genetic variants in two different genes, KRT25 and SP6, are responsible for curly hair. All horses with KRT25 variant are additionally hypotrichotic due to the KRT25 epistatic effect on SP6.


Assuntos
Pelo Animal/química , Epistasia Genética , Cavalos/genética , Hipotricose/genética , Queratinas Específicas do Cabelo/genética , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição Sp/genética , Animais , Cromossomos de Mamíferos , Estudo de Associação Genômica Ampla , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Cavalos/fisiologia , Fenótipo
9.
Genet Sel Evol ; 49(1): 85, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-29141579

RESUMO

BACKGROUND: Curly horses present a variety of curl phenotypes that are associated with various degrees of curliness of coat, mane, tail and ear hairs. Their origin is still a matter of debate and several genetic hypotheses have been formulated to explain the diversity in phenotype, including the combination of autosomal dominant and recessive alleles. Our purpose was to map the autosomal dominant curly hair locus and identify the causal variant using genome-wide association study (GWAS) and whole-genome sequencing approaches. RESULTS: A GWAS was performed using a Bayesian sparse linear mixed model, based on 51 curly and 19 straight-haired French and North American horses from 13 paternal families genotyped on the Illumina EquineSNP50 BeadChip. A single strong signal was observed on equine chromosome 11, in a region that encompasses the type I keratin gene cluster. This region was refined by haplotype analysis to a segment including 36 genes, among which are 10 keratin genes (KRT-10, -12, -20, -23, -24, -25, -26, -27, -28, -222). To comprehensively identify candidate causal variants within all these genes, whole-genome sequences were obtained for one heterozygous curly stallion and its straight-haired son. Among the four non-synonymous candidate variants identified and validated in the curly region, only variant g.21891160G>A in the KRT25 gene (KRT25:p.R89H) was in perfect agreement with haplotype status in the whole pedigree. Genetic association was then confirmed by genotyping a larger population consisting of 353 horses. However, five discordant curly horses were observed, which carried neither the variant nor the main haplotype associated with curliness. Sequencing of KRT25 for two discordant horses did not identify any other deleterious variant, which suggests locus rather than allelic heterogeneity for the curly phenotype. CONCLUSIONS: We identified the KRT25:p.R89H variant as responsible for the dominant curly trait, but a second dominant locus may also be involved in the shape of hairs within North American Curly horses.


Assuntos
Estudo de Associação Genômica Ampla/métodos , Cavalos/genética , Queratinas Específicas do Cabelo/genética , Mutação de Sentido Incorreto/genética , Animais , Teorema de Bayes , Cromossomos Humanos Par 11/genética , Genótipo , Haplótipos/genética , Heterozigoto , Humanos , Fenótipo
10.
Biotechniques ; 63(3): 131-134, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28911317

RESUMO

Biological evaluation of hair growth/differentiation activity in vitro has been a formidable challenge, primarily due to the lack of relevant model cell systems. To solve this problem, we generated a stable model cell line in which successive differentiation via epidermal progenitors to hair components is easily inducible and traceable. Mouse induced pluripotent stem (iPS) cell-derived cells were selected to stably express a tetracycline (Tet)-inducible bone morphogenic protein-4 (BMP4) expression cassette and a luciferase reporter driven by a hair-specific keratin 31 gene (krt31) promoter (Tet-BMP4-KRT31-Luc iPS). While Tet- BMP4-KRT31-Luc iPS cells could be maintained as stable iPS cells, the cells differentiated to produce luciferase luminescence in the presence of all-trans retinoic acid (RA) and doxycycline (Dox), and addition of a hair differentiation factor significantly increased luciferase fluorescence. Thus, this cell line may provide a reliable cell-based screening system to evaluate drug candidates for hair differentiation activity.


Assuntos
Alopecia/terapia , Diferenciação Celular , Engenharia Celular/métodos , Cabelo/citologia , Cabelo/crescimento & desenvolvimento , Células-Tronco Pluripotentes Induzidas/citologia , Animais , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 4/metabolismo , Linhagem Celular , Doxiciclina/farmacologia , Avaliação Pré-Clínica de Medicamentos , Células-Tronco Pluripotentes Induzidas/metabolismo , Queratinas Específicas do Cabelo/genética , Queratinas Específicas do Cabelo/metabolismo , Queratinas Tipo I/genética , Queratinas Tipo I/metabolismo , Luciferases/metabolismo , Substâncias Luminescentes/metabolismo , Camundongos , Regiões Promotoras Genéticas , Tetraciclina/farmacologia , Tretinoína/farmacologia
11.
Biopolymers ; 107(10)2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28741310

RESUMO

In the past two decades, keratin biomaterials have shown impressive results as scaffolds for tissue engineering, wound healing, and nerve regeneration. In addition to its intrinsic biocompatibility, keratin interacts with specific cell receptors eliciting beneficial biochemical cues. However, during extraction from natural sources, such as hair and wool fibers, natural keratins are subject to extensive processing conditions that lead to formation of unwanted by-products. Additionally, natural keratins suffer from limited sequence tunability. Recombinant keratin proteins can overcome these drawbacks while maintaining the desired chemical and physical characteristics of natural keratins. Herein, we present the bacterial expression, purification, and solution characterization of human hair keratins K31 and K81. The obligate heterodimerization of the K31/K81 pair that results in formation of intermediate filaments is maintained in the recombinant proteins. Surprisingly, we have for the first time observed new zero- and one-dimensional nanostructures from homooligomerization of K81 and K31, respectively. Further analysis of the self-assembly mechanism highlights the importance of disulfide crosslinking in keratin self-assembly.


Assuntos
Biopolímeros/química , Queratinas Específicas do Cabelo/química , Proteínas Recombinantes/química , Engenharia Tecidual , Biopolímeros/genética , Humanos , Queratinas Específicas do Cabelo/genética , Nanoestruturas/química , Multimerização Proteica , Proteínas Recombinantes/genética
12.
DNA Cell Biol ; 36(7): 552-564, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28509589

RESUMO

As an important commercial trait for sheep, curly fleece has a great economic impact on production costs and efficiency in sheep industry. To identify genes that are important for curly fleece formation in mammals, a suppression subtractive hybridization analysis was performed on the shoulder skin tissues exposed to two different growth stages of Chinese Tan sheep with different phenotypes (curly fleece and noncurling fleece). BLAST analysis identified 67 differentially expressed genes, of which 31 were expressed lower and 36 were expressed higher in lambs than in adult sheep. Differential expressions of seven randomly selected genes were verified using quantitative real-time polymerase chain reaction (qRT-PCR). KRT71 gene was selected for further study due to its high correlation with the curly hair phenotype in various mammal species. Semi-qPCR showed distinctively high expression of KRT71 in skin tissues. Moreover, qPCR result showed a significantly higher expression of KRT71 in curly fleece than noncurling Tan sheep. The luciferase assay and electrophoresis mobility shift assay showed that there were transcription factor binding sites in the promoter region of KRT71 related to the differential expression of KRT71 at the two growth stages of Tan sheep. Online bioinformation tools predicted MFZ1 as a transcriptional factor that regulates the expression of KRT71. These studies on KRT71 gene revealed some mechanisms underlying the relationship between the KRT71 gene and the curly fleece phenotype of Tan sheep.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Cabelo/metabolismo , Queratinas Específicas do Cabelo/genética , Característica Quantitativa Herdável , Fatores de Transcrição/genética , Fatores Etários , Animais , Sítios de Ligação , Perfilação da Expressão Gênica , Biblioteca Gênica , Ontologia Genética , Genes Reporter , Cabelo/anatomia & histologia , Cabelo/crescimento & desenvolvimento , Humanos , Queratinas Específicas do Cabelo/metabolismo , Luciferases/genética , Luciferases/metabolismo , Anotação de Sequência Molecular , Fenótipo , Regiões Promotoras Genéticas , Ligação Proteica , Carneiro Doméstico , Técnicas de Hibridização Subtrativa , Fatores de Transcrição/metabolismo
13.
Oncol Rep ; 37(5): 2964-2970, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28405679

RESUMO

Keratins are fibrous proteins. Hair keratins constitute hard structures such as the hair and nails, and cytokeratins have been used as markers of breast carcinoma. However, the expression and function of full-size hair keratin genes have not been previously demonstrated in breast cancer. We investigated the expression of the hair keratin, KRT81, and its function in human breast cancer and normal mammary epithelial cells. Western blotting showed full size 55-kDa KRT81 expression in the human breast cancer cell lines, MCF7, SKBR3 and MDA-MB-231, normal human mammary epithelial cells (HMEC), and non-neoplastic cells (MCF10A). Reverse transcription-polymerase chain reaction revealed that the full size KRT81, including its 5' region is expressed in breast cells. Immunohistochemical and immunofluorescence analyses showed that KRT81 was located in the cytoplasm. To investigate the function of KRT81, we knocked down KRT81 by siRNA in MCF10A cells. Microarray analysis revealed that the expression of genes related to invasion such as matrix metallopeptidase (MMP)9 was decreased. In KRT81-knockdown MDA-MB231 cells, zymography revealed a decrease in MMP9 activity, while scratch and invasion assays revealed that KRT81-knockdown decreased cell migration and invasion abilities. This is the first study showing that full size KRT81 is expressed in normal breast epithelial cells and breast cancer cells. Moreover, our results indicate that KRT81 contributes to the migration and invasion of breast cancer cells.


Assuntos
Neoplasias da Mama/metabolismo , Queratinas Específicas do Cabelo/genética , Queratinas Específicas do Cabelo/metabolismo , Queratinas Tipo II/genética , Queratinas Tipo II/metabolismo , Glândulas Mamárias Humanas/metabolismo , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Movimento Celular , Citoplasma/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Invasividade Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos/métodos
15.
J Med Genet ; 54(3): 186-189, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27965375

RESUMO

BACKGROUND: Progressive symmetric erythrokeratoderma (PSEK) is a rare skin disorder characterised by symmetrically distributed demarcated hyperkeratotic plaques, often with associated palmoplantar hyperkeratosis, with new plaques appearing over time. Most cases are inherited in an autosomal dominant manner, although a few cases exhibit apparent autosomal recessive inheritance. OBJECTIVE: To identify the gene underlying autosomal recessive PSEK in a large Pakistani kindred. METHODS: We first carried out autozygosity mapping using microsatellite markers in candidate regions of the genome. We then carried out exome sequencing of five family members, autozygosity mapping and mutation analysis using the exome data and verification by Sanger sequencing. RESULTS: Autozygosity mapping and exome sequencing identified a homozygous frameshift deletion (c.811delA; p.Ser271fs) in KRT83, which co-segregated with the PSEK phenotype in the family and which is expected to abolish keratin 83, a type II keratin of hair and skin. CONCLUSIONS: At least some cases of PSEK result from loss-of-function mutations in KRT83. Heterozygous missense substitutions in KRT83 have been implicated in autosomal dominant monilethrix, a rare hair disorder. Our findings indicate that at least some cases of autosomal recessive PSEK and autosomal dominant monilethrix are allelic, respectively resulting from loss-of-function and missense mutations in the KRT83 gene. Together, these findings indicate that different types of mutations in KRT83 can result in quite different skin and hair phenotypes.


Assuntos
Eritroceratodermia Variável/genética , Queratinas Específicas do Cabelo/genética , Queratinas Tipo II/genética , Monilétrix/genética , Alelos , Eritroceratodermia Variável/patologia , Exoma/genética , Feminino , Cabelo/metabolismo , Cabelo/patologia , Heterozigoto , Homozigoto , Humanos , Masculino , Monilétrix/patologia , Mutação de Sentido Incorreto , Paquistão , Linhagem , Fenótipo , Deleção de Sequência , Pele/metabolismo , Pele/patologia
16.
PLoS One ; 11(4): e0153936, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27100288

RESUMO

The keratin-associated proteins (KAPs) are the structural proteins of hair fibers and are thought to play an important role in determining the physical properties of hair fibers. These proteins are activated in a striking sequential and spatial pattern in the keratinocytes of hair fibers. Thus, it is important to elucidate the mechanism that underlies the specific transcriptional activity of these genes. In this study, sheep KRTAP 3-3 and KRTAP11-1 genes were found to be highly expressed in wool follicles in a tissue-specific manner. Subsequently, the promoter regions of the two genes that contained the 5' flanking/5' untranslated regions and the coding regions were cloned. Using an in vivo transgenic approach, we found that the promoter regions from the two genes exhibited transcriptional activity in hair fibers. A much stronger and more uniformly expressed green fluorescent signal was observed in the KRTAP11-1-ZsGreen1 transgenic mice. In situ hybridization revealed the symmetrical expression of sheep KRTAP11-1 in the entire wool cortex. Consistently, immunohistochemical analysis demonstrated that the pattern of ZsGreen1 expression in the hair cortex of transgenic mice matches that of the endogenous KRTAP11-1 gene, indicating that the cloned promoter region contains elements that are sufficient to govern the wool cortex-specific transcription of KRTAP11-1. Furthermore, regulatory regions in the 5' upstream sequence of the sheep KRTAP11-1 gene that may regulate the observed hair keratinocyte specificity were identified using in vivo reporter assays.


Assuntos
Biomarcadores/metabolismo , Regulação da Expressão Gênica , Cabelo/metabolismo , Queratinas Específicas do Cabelo/genética , Regiões Promotoras Genéticas/genética , Animais , Clonagem Molecular , Feminino , Perfilação da Expressão Gênica , Técnicas Imunoenzimáticas , Hibridização In Situ , Queratinas Específicas do Cabelo/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Filogenia , Ovinos
17.
J Invest Dermatol ; 136(6): 1097-1105, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26902920

RESUMO

Hypotrichosis is an abnormal condition characterized by decreased hair density and various defects in hair structure and growth patterns. In particular, in woolly hair, hypotrichosis is characterized by a tightly curled structure and abnormal growth. In this study, we present a detailed comparative examination of individuals affected by autosomal-recessive hypotrichosis (ARH), which distinguishes two types of ARH. Earlier, we demonstrated that exon 4 deletion in the lipase H gene caused an ARH (hypotrichosis 7; MIM: 604379) in populations of the Volga-Ural region of Russia. Screening for this mutation in all affected individuals revealed its presence only in the group with the hypotrichosis 7 phenotype. Other patients formed a separate group of woolly hair-associated ARH, with a homozygous missense mutation c.712G>T (p.Val238Leu) in a highly conserved position of type I keratin KRT25 (K25). Haplotype analysis indicated a founder effect. An expression study in the HaCaT cell line demonstrated a deleterious effect of the p.Val238Leu mutation on the formation of keratin intermediate filaments. Hence, we have identified a previously unreported missense mutation in the KRT25 gene causing ARH with woolly hair.


Assuntos
Alopecia/congênito , Predisposição Genética para Doença/epidemiologia , Queratinas Específicas do Cabelo/genética , Mutação de Sentido Incorreto , Alopecia/etnologia , Alopecia/genética , Análise Mutacional de DNA , Éxons/genética , Feminino , Genes Recessivos , Cabelo/anormalidades , Doenças do Cabelo , Folículo Piloso/patologia , Haplótipos/genética , Humanos , Masculino , Linhagem , Fenótipo , Federação Russa , Amostragem , Deleção de Sequência
18.
Matrix Biol ; 52-54: 260-265, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26709044

RESUMO

Dental enamel is the hardest tissue in the human body, and although it starts as a tissue rich in proteins, by the time of eruption of the tooth in the oral cavity only a small fraction of the protein remains. While this organic matrix of enamel represents less than 1% by weight it plays essential roles in improving both toughness and resilience to chemical attacks. Despite the fact that the first studies of the enamel matrix began in the 19th century, its exact composition and mechanisms of its function remain poorly understood. It was proposed that keratin or a keratin-like primitive epithelial component exists in mature enamel, however due to the extreme insolubility of its organic matrix the presence of keratins there was never clearly established. We have recently identified expression of a number of hair keratins in ameloblasts, the enamel secreting cells, and demonstrated their incorporation into mature enamel. Mutation in epithelial hair keratin KRT75 leads to a skin condition called pseudofollicularis barbae. Carriers of this mutation have an altered enamel structure and mechanical properties. Importantly, these individuals have a much higher prevalence of caries. To the best of our knowledge, this is the first study showing a direct link between a mutation in a protein-coding region of a gene and increased caries rates. In this paper we present an overview of the evidence of keratin-like material in enamel that has accumulated over the last 150years. Furthermore, we propose potential mechanisms of action of KTR75 in enamel and highlight the clinical implications of the link between mutations in KRT75 and caries. Finally, we discuss the potential use of keratins for enamel repair.


Assuntos
Cárie Dentária/epidemiologia , Esmalte Dentário/química , Queratinas Específicas do Cabelo/genética , Queratinas Específicas do Cabelo/metabolismo , Queratinas Tipo II/genética , Queratinas Tipo II/metabolismo , Animais , Cárie Dentária/genética , Cárie Dentária/metabolismo , Esmalte Dentário/metabolismo , Esmalte Dentário/patologia , Doenças do Cabelo/complicações , Doenças do Cabelo/genética , Humanos , Mutação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA