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1.
BMC Pregnancy Childbirth ; 24(1): 456, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951757

RESUMO

BACKGROUND: TBX6, a member of the T-box gene family, encodes the transcription factor box 6 that is critical for somite segmentation in vertebrates. It is known that the compound heterozygosity of disruptive variants in trans with a common hypomorphic risk haplotype (T-C-A) in the TBX6 gene contribute to 10% of congenital scoliosis (CS) cases. The deletion of chromosome 17q12 is a rare cytogenetic abnormality, which often leads to renal cysts and diabetes mellitus. However, the affected individuals often exhibit clinical heterogeneity and incomplete penetrance. METHODS: We here present a Chinese fetus who was shown to have CS by ultrasound examination at 17 weeks of gestation. Trio whole-exome sequencing (WES) was performed to investigate the underlying genetic defects of the fetus. In vitro functional experiments, including western-blotting and luciferase transactivation assay, were performed to determine the pathogenicity of the novel variant of TBX6. RESULTS: WES revealed the fetus harbored a compound heterozygous variant of c.338_340del (p.Ile113del) and the common hypomorphic risk haplotype of the TBX6 gene. In vitro functional study showed the p.Ile113del variant had no impact on TBX6 expression, but almost led to complete loss of its transcriptional activity. In addition, we identified a 1.85 Mb deletion on 17q12 region in the fetus and the mother. Though there is currently no clinical phenotype associated with this copy number variation in the fetus, it can explain multiple renal cysts in the pregnant woman. CONCLUSIONS: This study is the first to report a Chinese fetus with a single amino acid deletion variant and a T-C-A haplotype of TBX6. The clinical heterogeneity of 17q12 microdeletion poses significant challenges for prenatal genetic counseling. Our results once again suggest the complexity of prenatal genetic diagnosis.


Assuntos
Cromossomos Humanos Par 17 , Haplótipos , Heterozigoto , Proteínas com Domínio T , Humanos , Proteínas com Domínio T/genética , Feminino , Cromossomos Humanos Par 17/genética , Gravidez , Adulto , Deleção Cromossômica , Sequenciamento do Exoma , Deleção de Sequência , Feto/anormalidades , Ultrassonografia Pré-Natal
2.
Neuromolecular Med ; 26(1): 28, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954284

RESUMO

Neurofibromatosis type 1 (NF1) is a genetic disorder caused by mutations in the NF1 gene. This disorder shows nearly complete penetrance and high phenotypic variability. We used the whole-exome sequencing technique to identify mutations in 32 NF1 cases from 22 Iranian families. A total of 31 variants, including 30 point mutations and one large deletion, were detected. In eight cases, variants were inherited, while they were sporadic in the remaining. Seven novel variants, including c.5576 T > G, c.6658_6659insC, c.2322dupT, c.92_93insAA, c.4360C > T, c.3814C > T, and c.4565_4566delinsC, were identified. The current study is the largest in terms of the sample size of Iranian NF1 cases with identified mutations. The results can broaden the spectrum of NF1 mutations and facilitate the process of genetic counseling in the affected families.


Assuntos
Sequenciamento do Exoma , Genes da Neurofibromatose 1 , Neurofibromatose 1 , Neurofibromina 1 , Humanos , Irã (Geográfico) , Neurofibromatose 1/genética , Neurofibromina 1/genética , Feminino , Masculino , Criança , Linhagem , Adulto , Mutação Puntual , Mutação , Adolescente , Pré-Escolar , Adulto Jovem , Análise Mutacional de DNA , Deleção de Sequência
3.
Mol Plant Pathol ; 25(7): e13490, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38952297

RESUMO

Employing race-specific resistance genes remains an effective strategy to protect wheat from leaf rust caused by Puccinia triticina (Pt) worldwide, while the newly emerged Pt races, owing to rapid genetic evolution, frequently overcome the immune response delivered by race-specific resistance genes. The molecular mechanisms underlying the newly evolved virulence Pt pathogen remain unknown. Here, we identified an avirulence protein AvrLr15 from Pt that induced Lr15-dependent immune responses. Heterologously produced AvrLr15 triggered pronounced cell death in Lr15-isogenic wheat leaves. AvrLr15 contains a functional signal peptide, localized to the plant nucleus and cytosol and can suppress BAX-induced cell death. Evasion of Lr15-mediated resistance in wheat was associated with a deletion and point mutations of amino acids in AvrLr15 rather than AvrLr15 gene loss in the Lr15-breaking Pt races, implying that AvrLr15 is required for the virulence function of Pt. Our findings identified the first molecular determinant of wheat race-specific immunity and facilitated the identification of the first AVR/R gene pair in the Pt-wheat pathosystem, which will provide a molecular marker to monitor natural Pt populations and guide the deployment of Lr15-resistant wheat cultivars in the field.


Assuntos
Resistência à Doença , Doenças das Plantas , Puccinia , Triticum , Triticum/microbiologia , Triticum/genética , Triticum/imunologia , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Resistência à Doença/genética , Puccinia/patogenicidade , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Genes de Plantas , Virulência/genética , Mutação/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Basidiomycota/patogenicidade , Basidiomycota/genética , Folhas de Planta/microbiologia , Folhas de Planta/imunologia , Morte Celular , Deleção de Sequência/genética
4.
Arch Virol ; 169(8): 158, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38970647

RESUMO

The highly pathogenic genotype 2b (HP-G2b) of porcine epidemic diarrhea virus (PEDV), which caused a pandemic in 2013-2014, evolved in South Korea and became endemic, affecting the domestic pig industry. This study describes the genotypic traits of novel HP-G2b PEDV strains identified on affected farms experiencing low disease severity with < 10% neonatal mortality. Nucleotide sequencing revealed common deletion patterns, termed S-DEL2, resulting in a two-amino-acid deletion at positions 60 and 61, 61 and 62, or 63 and 64 in the N-terminal domain of the spike (S) protein of all isolates. The S barcode profiles of S-DEL2 variants differed from each other and shared 96.0-99.4% and 98.5-99.6% nt sequence identity with other South Korean HP-G2b PEDV strains in the S gene and in the complete genome sequence, respectively. Genetic and phylogenetic analysis showed that the S-DEL2 strains belonged to diverse domestic clades: CK, CK.1, CK.2, or NC. The emergence of novel S-DEL2 strains suggests that continuous evolution of PEDV occurs under endemic circumstances, resulting in genetic diversity and distinct clinical presentations. This study advances our knowledge regarding the genetic and pathogenic heterogeneity of PEDV and emphasizes the importance of active monitoring and surveillance to identify novel variants and determine their genotypic and phenotypic characteristics.


Assuntos
Infecções por Coronavirus , Genótipo , Filogenia , Vírus da Diarreia Epidêmica Suína , Glicoproteína da Espícula de Coronavírus , Doenças dos Suínos , Vírus da Diarreia Epidêmica Suína/genética , Vírus da Diarreia Epidêmica Suína/classificação , Vírus da Diarreia Epidêmica Suína/isolamento & purificação , Animais , República da Coreia/epidemiologia , Suínos , Doenças dos Suínos/virologia , Doenças dos Suínos/epidemiologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Infecções por Coronavirus/epidemiologia , Glicoproteína da Espícula de Coronavírus/genética , Variação Genética , Genoma Viral/genética , Deleção de Sequência
6.
HLA ; 103(6): e15546, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38887907

RESUMO

A nucleotide deletion in the residue 371 of HLA-A*11:01:01:01 results in a novel allele HLA-A*11:466N.


Assuntos
Éxons , Antígeno HLA-A11 , Teste de Histocompatibilidade , Humanos , Alelos , Sequência de Bases , Códon , Antígeno HLA-A11/genética , Alinhamento de Sequência , Análise de Sequência de DNA , Deleção de Sequência , Taiwan
7.
Hematology ; 29(1): 2365596, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38864494

RESUMO

OBJECTIVES: This study aimed to establish a droplet digital polymerase chain reaction (ddPCR) assay for South-East Asian (SEA) deletion based on a fully integrated digital PCR system DropXpert S6. METHODS: A total of 151 whole blood samples, 10 chorionic villus samples, and 17 amniotic fluid samples were collected, including 106 SEA heterozygotes, 43 normal individuals, 10 Hb Bart's hydrops details, and 19 SEA deletions combined with other genotypes.Genotypes of these samples were determined by the Gap-PCR method. We perform a series of optimizations of the ddPCR system to ensure the performance of the entire ddPCR reaction, such as droplet stability, fluorescence clustering, sensitivity, and accuracy. RESULTS: Our assay exhibited 99.4% (177/178) accuracy compared with the Gap-PCR method, and the minimum detection limit of DNA was 0.1 ng/µL.Both targets have reliable linearity, R2 = 0.9999 for the α-thalassemia SEA deletion allele and R2 = 1 for the wild-type allele. The coefficient of variation for α-thalassemia SEA deletion allele detection at 2 and 10 ng/µL concentrations was 5.42% and 1.91%, respectively. In contrast, the coefficient of variation for wild-type allele detection was 4.06% and 1.83%, demonstrating its high quantitative accuracy. In addition, the DropXpert S6 PCR system showed some advantages over other ddPCR instruments, such as reducing testing costs, simplifying and automating the workflow. CONCLUSIONS: The DropXpert S6 PCR system provided a highly accurate diagnosis for α-thalassemia SEA deletion and can be used to detect α-thalassemia as an alternative method.


Assuntos
Reação em Cadeia da Polimerase , Talassemia alfa , Talassemia alfa/genética , Talassemia alfa/diagnóstico , Talassemia alfa/sangue , Humanos , Reação em Cadeia da Polimerase/métodos , Feminino , Sudeste Asiático , Deleção de Sequência , Povo Asiático/genética , População do Leste Asiático
10.
Int J Mol Sci ; 25(12)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38928189

RESUMO

Plants photoreceptors perceive changes in light quality and intensity and thereby regulate plant vegetative growth and reproductive development. By screening a γ irradiation-induced mutant library of the soybean (Glycine max) cultivar "Dongsheng 7", we identified Gmeny, a mutant with elongated nodes, yellowed leaves, decreased chlorophyll contents, altered photosynthetic performance, and early maturation. An analysis of bulked DNA and RNA data sampled from a population segregating for Gmeny, using the BVF-IGV pipeline established in our laboratory, identified a 10 bp deletion in the first exon of the candidate gene Glyma.02G304700. The causative mutation was verified by a variation analysis of over 500 genes in the candidate gene region and an association analysis, performed using two populations segregating for Gmeny. Glyma.02G304700 (GmHY2a) is a homolog of AtHY2a in Arabidopsis thaliana, which encodes a PΦB synthase involved in the biosynthesis of phytochrome. A transcriptome analysis of Gmeny using the Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed changes in multiple functional pathways, including photosynthesis, gibberellic acid (GA) signaling, and flowering time, which may explain the observed mutant phenotypes. Further studies on the function of GmHY2a and its homologs will help us to understand its profound regulatory effects on photosynthesis, photomorphogenesis, and flowering time.


Assuntos
Éxons , Regulação da Expressão Gênica de Plantas , Glycine max , Hipocótilo , Fotossíntese , Glycine max/genética , Glycine max/crescimento & desenvolvimento , Glycine max/metabolismo , Fotossíntese/genética , Éxons/genética , Hipocótilo/genética , Hipocótilo/crescimento & desenvolvimento , Deleção de Sequência , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Giberelinas/metabolismo , Perfilação da Expressão Gênica , Fenótipo
11.
Viruses ; 16(6)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38932154

RESUMO

We previously reported that deletion of a 44-nucleotide element in the 3' untranslated region (UTR) of the Chikungunya virus (CHIKV) genome enhances the virulence of CHIKV infection in mice. Here, we find that while this 44-nucleotide deletion enhances CHIKV fitness in murine embryonic fibroblasts in a manner independent of the type I interferon response, the same mutation decreases viral fitness in C6/36 mosquito cells. Further, the fitness advantage conferred by the UTR deletion in mammalian cells is maintained in vivo in a mouse model of CHIKV dissemination. Finally, SHAPE-MaP analysis of the CHIKV 3' UTR revealed this 44-nucleotide element forms a distinctive two-stem-loop structure that is ablated in the mutant 3' UTR without altering additional 3' UTR RNA secondary structures.


Assuntos
Regiões 3' não Traduzidas , Febre de Chikungunya , Vírus Chikungunya , Replicação Viral , Vírus Chikungunya/genética , Vírus Chikungunya/fisiologia , Animais , Camundongos , Febre de Chikungunya/virologia , RNA Viral/genética , Virulência , Linhagem Celular , Fibroblastos/virologia , Aptidão Genética , Humanos , Deleção de Sequência , Conformação de Ácido Nucleico , Modelos Animais de Doenças
12.
Mol Genet Genomic Med ; 12(6): e2475, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38938072

RESUMO

BACKGROUND: Spastic paraplegia 11 (SPG11) is the most prevalent form of autosomal recessive hereditary spastic paraplegia, resulting from biallelic pathogenic variants in the SPG11 gene (MIM *610844). METHODS: The proband is a 36-year-old female referred for genetic evaluation due to cognitive dysfunction, gait impairment, and corpus callosum atrophy (brain MRI was normal at 25-years-old). Diagnostic approaches included CGH array, next-generation sequencing, and whole transcriptome sequencing. RESULTS: CGH array revealed a 180 kb deletion located upstream of SPG11. Sequencing of SPG11 uncovered two rare single nucleotide variants: the novel variant c.3143C>T in exon 17 (in cis with the deletion), and the previously reported pathogenic variant c.6409C>T in exon 34 (in trans). Whole transcriptome sequencing revealed that the variant c.3143C>T caused exon 17 skipping. CONCLUSION: We report a novel sequence variant in the SPG11 gene resulting in exon 17 skipping, which, along with a nonsense variant, causes Spastic Paraplegia 11 in our proband. In addition, a deletion upstream of SPG11 was identified in the patient, whose implication in the phenotype remains uncertain. Nonetheless, the deletion apparently affects cis-regulatory elements of the gene, suggesting a potential new pathogenic mechanism underlying the disease in a subset of undiagnosed patients. Our findings further support the hypothesis that the origin of thin corpus callosum in patients with SPG11 is of progressive nature.


Assuntos
Paraplegia Espástica Hereditária , Humanos , Feminino , Adulto , Paraplegia Espástica Hereditária/genética , Paraplegia Espástica Hereditária/diagnóstico , Paraplegia Espástica Hereditária/patologia , Éxons , Proteínas/genética , Códon sem Sentido , Corpo Caloso/patologia , Corpo Caloso/diagnóstico por imagem , Deleção de Sequência , Fenótipo
13.
Vet Res ; 55(1): 73, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849962

RESUMO

African swine fever virus (ASFV) causes a devastating disease affecting domestic and wild pigs. ASF was first introduced in Sardinia in 1978 and until 2019 only genotype I isolates were identified. A remarkable genetic stability of Sardinian ASFV isolates was described, nevertheless in 2019 two wild boar isolates with a sustained genomic deletion (4342 base pairs) were identified (7303WB/19, 7212WB/19). In this study, we therefore performed in vitro experiments with monocyte-derived macrophages (moMФ) to unravel the phenotypic characteristics of these deleted viruses. Both 7303WB/19 and 7212WB/19 presented a lower growth kinetic in moMФ compared to virulent Sardinian 26544/OG10, using either a high (1) or a low (0.01) multiplicity of infection (MOI). In addition, flow cytometric analysis showed that both 7303WB/19 and 7212WB/19 presented lower intracellular levels of both early and late ASFV proteins. We subsequently investigated whether deleted virus variants were previously circulating in wild boars in Sardinia. In the four years preceding the last genotype I isolation (February 2015-January 2019), other eight wild boar isolates were collected, all belonging to p72 genotype I, B602L subgroup X, but none of them presented a sustained genomic deletion. Overall, we observed the deleted virus isolates in Sardinia only in 2019, at the end of a strong eradication campaign, and our data suggest that it might possess an attenuated phenotype in vivo. A better understanding of ASFV evolution in endemic territories might contribute to development of effective control measures against ASF.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Genótipo , Sus scrofa , Animais , Vírus da Febre Suína Africana/genética , Vírus da Febre Suína Africana/fisiologia , Suínos , Itália , Febre Suína Africana/virologia , Genoma Viral , Fenótipo , Deleção de Sequência , Macrófagos/virologia
14.
Brief Bioinform ; 25(4)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38851298

RESUMO

Deletion is a crucial type of genomic structural variation and is associated with numerous genetic diseases. The advent of third-generation sequencing technology has facilitated the analysis of complex genomic structures and the elucidation of the mechanisms underlying phenotypic changes and disease onset due to genomic variants. Importantly, it has introduced innovative perspectives for deletion variants calling. Here we propose a method named Dual Attention Structural Variation (DASV) to analyze deletion structural variations in sequencing data. DASV converts gene alignment information into images and integrates them with genomic sequencing data through a dual attention mechanism. Subsequently, it employs a multi-scale network to precisely identify deletion regions. Compared with four widely used genome structural variation calling tools: cuteSV, SVIM, Sniffles and PBSV, the results demonstrate that DASV consistently achieves a balance between precision and recall, enhancing the F1 score across various datasets. The source code is available at https://github.com/deconvolution-w/DASV.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Software , Humanos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Deleção de Sequência , Análise de Sequência de DNA/métodos , Algoritmos , Genômica/métodos , Biologia Computacional/métodos
15.
Mol Biol Rep ; 51(1): 612, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38704770

RESUMO

BACKGROUND: The α-Major Regulatory Element (α-MRE), also known as HS-40, is located upstream of the α-globin gene cluster and has a crucial role in the long-range regulation of the α-globin gene expression. This enhancer is polymorphic and several haplotypes were identified in different populations, with haplotype D almost exclusively found in African populations. The purpose of this research was to identify the HS-40 haplotype associated with the 3.7 kb α-thalassemia deletion (-α3.7del) in the Portuguese population, and determine its ancestry and influence on patients' hematological phenotype. METHODS AND RESULTS: We selected 111 Portuguese individuals previously analyzed by Gap-PCR to detect the presence of the -α3.7del: 50 without the -α3.7del, 34 heterozygous and 27 homozygous for the -α3.7del. The HS-40 region was amplified by PCR followed by Sanger sequencing. Four HS-40 haplotypes were found (A to D). The distribution of HS-40 haplotypes and genotypes are significantly different between individuals with and without the -α3.7del, being haplotype D and genotype AD the most prevalent in patients with this deletion in homozygosity. Furthermore, multiple correspondence analysis revealed that individuals without the -α3.7del are grouped with other European populations, while samples with the -α3.7del are separated from these and found more closely related to the African population. CONCLUSION: This study revealed for the first time an association of the HS-40 haplotype D with the -α3.7del in the Portuguese population, and its likely African ancestry. These results may have clinical importance as in vitro analysis of haplotype D showed a decrease in its enhancer activity on α-globin gene.


Assuntos
Haplótipos , Deleção de Sequência , alfa-Globinas , Talassemia alfa , Feminino , Humanos , Masculino , alfa-Globinas/genética , Talassemia alfa/genética , População Negra/genética , Frequência do Gene/genética , Genótipo , Haplótipos/genética , Portugal , Sequências Reguladoras de Ácido Nucleico/genética , Deleção de Sequência/genética
16.
PLoS Genet ; 20(5): e1011297, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38787916

RESUMO

Genotype data include errors that may influence conclusions reached by downstream statistical analyses. Previous studies have estimated genotype error rates from discrepancies in human pedigree data, such as Mendelian inconsistent genotypes or apparent phase violations. However, uncalled deletions, which generally have not been accounted for in these studies, can lead to biased error rate estimates. In this study, we propose a genotype error model that considers both genotype errors and uncalled deletions when calculating the likelihood of the observed genotypes in parent-offspring trios. Using simulations, we show that when there are uncalled deletions, our model produces genotype error rate estimates that are less biased than estimates from a model that does not account for these deletions. We applied our model to SNVs in 77 sequenced White British parent-offspring trios in the UK Biobank. We use the Akaike information criterion to show that our model fits the data better than a model that does not account for uncalled deletions. We estimate the genotype error rate at SNVs with minor allele frequency > 0.001 in these data to be [Formula: see text]. We estimate that 77% of the genotype errors at these markers are attributable to uncalled deletions [Formula: see text].


Assuntos
Genótipo , Sequenciamento Completo do Genoma , Humanos , Polimorfismo de Nucleotídeo Único/genética , Modelos Genéticos , Frequência do Gene , Genoma Humano , Linhagem , Deleção de Sequência , Simulação por Computador
18.
PLoS One ; 19(5): e0304331, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38820426

RESUMO

Quorum sensing can induce density-dependent gene expressions that cause various problems. For quorum-sensing inhibition, fundamental solutions such as gene manipulation are required, and acyl-homoserine lactone synthase (AHL synthase), which synthesizes the universal quorum-sensing signal of gram-negative bacteria, can be used as a target. In this study, researchers synthesized His-tagged AHL synthase and its deletion mutant that lacks the active site and compared their biochemical characteristics. His-YpeI, the 6x His-tagged AHL synthase of Serratia fonticola, and His-ΔYpeI, its deletion mutant, were designed, and their property conservation were examined using in silico projection tools. For in vitro synthesis of enzymes, the His-YpeI CFPS template was synthesized by in vitro gene synthesis, and the His-ΔYpeI CFPS template was obtained by deletion PCR. CFPS was performed and the products were purified with the 6x His-tag. The enzymes' properties were compared using an enzymatic assay. The bioinformatic analysis confirmed the conservation of biochemical properties between 6x His-tagged and untagged enzymes, including helix-turn-helix interactions, hydropathy profiles, and tertiary structure between His-YpeI and YpeI and between His-ΔYpeI and ΔYpeI. His-YpeI and His-ΔYpeI synthesized by CFPS were found to have the expected molecular weights and demonstrated distinct differences in enzyme activity. The analyzed enzymatic constants supported a significant decrease in substrate affinity and reaction rate as a result of YpeI's enzyme active site deletion. This result showed that CFPS could be used for in vitro protein synthesis, and quorum sensing could be inhibited at the enzymatic level due to the enzyme active site's deletion mutation.


Assuntos
Percepção de Quorum , Percepção de Quorum/genética , Aciltransferases/genética , Aciltransferases/metabolismo , Aciltransferases/química , Deleção de Sequência , Serratia/enzimologia , Serratia/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Domínio Catalítico , Sequência de Aminoácidos , Ligases
19.
Anim Genet ; 55(4): 676-680, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38721753

RESUMO

Cats with a distinctive white hair pattern of unknown molecular cause have been discovered in the Finnish domestic cat population. Based on the unique appearance of these cats, we have named this phenotype salmiak ("salty licorice"). The use of a commercially available panel test to genotype four salmiak-colored cats revealed the absence of all known variants associated with white-haired phenotypic loci: full White (W), Spotting (Ws) and the Birman white Gloves associated (wg) allele of the KIT proto-oncogene (KIT) gene. Whole-genome sequencing on two salmiak-colored cats was conducted to search for candidate causal variants in the KIT gene. Despite a lack of coding variants, visual inspection of the short read alignments revealed a large ~95 kb deletion located ~65 kb downstream of the KIT gene in the salmiak cats. Additional PCR genotyping of 180 domestic cats and three salmiak-colored cats confirmed the homozygous derived variant genotype fully concordant with the salmiak phenotype. We suggest the newly identified variant be designated as wsal for "w salmiak".


Assuntos
Cor de Cabelo , Proteínas Proto-Oncogênicas c-kit , Animais , Gatos/genética , Cor de Cabelo/genética , Proteínas Proto-Oncogênicas c-kit/genética , Fenótipo , Deleção de Sequência , Finlândia , Genótipo , Sequenciamento Completo do Genoma/veterinária
20.
Anim Genet ; 55(4): 692-696, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38742646

RESUMO

Split paw pad disease is a scarcely defined phenotype characterized by skin lesions on the paw pads of dogs. We studied a family of German Shepherd dogs, in which four dogs developed intermittent paw pad lesions and lameness. The paw pads of two of the affected dogs were biopsied and demonstrated cleft formation in the stratum spinosum and stratum corneum, the outermost layers of the epidermis. Whole genome sequencing data from an affected dog revealed a private heterozygous 18 bp in frame deletion in the KRT5 gene. The deletion NM_001346035.1:c.988_1005del or NP_001332964.1:p.(Asn330_Asp335del) is predicted to lead to a loss of six amino acids in the L12 linker domain of the encoded keratin 5. KRT5 variants in human patients lead to various subtypes of epidermolysis bullosa simplex (EBS). Localized EBS is the mildest of the KRT5-related human diseases and may be caused by variants affecting the L12 linker domain of keratin 5. We therefore think that the detected KRT5 deletion in dogs represents a candidate causal variant for the observed skin lesions in dogs. However, while the clinical phenotype of KRT5-mutant dogs of this study closely resembles human patients with localized EBS, there are differences in the histopathology. EBS is defined by cleft formation within the basal layer of the epidermis while the cleft formation in the dogs described herein occurred in the outermost layers, a hallmark of split paw pad disease. Our study provides a basis for further studies into the exact relation of split paw pad disease and EBS.


Assuntos
Doenças do Cão , Epidermólise Bolhosa Simples , Queratina-5 , Animais , Cães , Queratina-5/genética , Doenças do Cão/genética , Epidermólise Bolhosa Simples/genética , Epidermólise Bolhosa Simples/veterinária , Epidermólise Bolhosa Simples/patologia , Deleção de Sequência , Fenótipo , Masculino , Linhagem , Feminino
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