scholarly journals Being Merle: The Molecular Genetic Background of the Canine Merle Mutation

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 660
Author(s):  
László Varga ◽  
Xénia Lénárt ◽  
Petra Zenke ◽  
László Orbán ◽  
Péter Hudák ◽  
...  
Keyword(s):  
Coat Color ◽  
Germ Line ◽  
Molecular Genetic ◽  
Cryptic Splice Site ◽  
Color Intensity ◽  
Replication Slippage ◽  
Color Formation ◽  
Cell Clones ◽  
Dark Color ◽  
Exon 11

The intensity of the merle pattern is determined by the length of the poly(A) tail of a repeat element which has been inserted into the boundary of intron 10 and exon 11 of the PMEL17 locus in reverse orientation. This poly(A) tail behaves as a microsatellite, and due to replication slippage, longer and shorter alleles of it might be generated during cell divisions. The length of the poly(A) tail regulates the splicing mechanism. In the case of shorter tails, the removal of intron 10 takes place at the original splicing, resulting in a normal premelanosome protein (PMEL). Longer tails generate larger insertions, forcing splicing to a cryptic splice site, thereby coding for an abnormal PMEL protein, which is unable to form the normal fibrillar matrix of the eumelanosomes. Thus, eumelanin deposition ensuring the dark color formation is reduced. In summary, the longer the poly(A) tail, the lighter the coat color intensity of the melanocytes. These mutations can occur in the somatic cells and the resulting cell clones will shape the merle pattern of the coat. When they take place in the germ line, they occasionally produce offspring with unexpected color variations which are different from those of their parents.

scholarly journals Screening of six risk exons of the RET proto-oncogene in families with medullary thyroid carcinoma in the Czech Republic

2004 ◽  
Vol 183 (2) ◽  
pp. 257-265 ◽  
Author(s):  
Š Jindřichová ◽  
J Včelák ◽  
P Vlček ◽  
M Neradilová ◽  
J Němec ◽  
...  
Keyword(s):  
Czech Republic ◽  
Genetic Testing ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Germ Line ◽  
Molecular Genetic ◽  
The Czech Republic ◽  
Medullary Thyroid ◽  
Germ Line Mutations ◽  
Exon 11

Medullary thyroid carcinoma (MTC) occurs as a sporadic form (75%) or as an autosomal dominant inherited familial disorder (25%) called familial MTC (FMTC) or as multiple endocrine neoplasia type 2 (MEN2) syndromes. Germ-line mutations in the rearranged during transfection (RET) proto-oncogene in exons 10, 11, 13, 14, 15 and 16 are known to be a cause of most of the familial forms. In this paper we report molecular genetic testing of 106 families with MTC (358 tested persons) from the Czech Republic in which we directly sequenced these six exons of the RET proto-oncogene. We detected germ-line mutations in 100% of MEN2B families (4/4 families), 90% of MEN2A families (9/10), 40% of FMTC families (4/10) and 7% of apparently sporadic MTC (6/82). Eleven different germ-line mutations were revealed. MEN2B was associated with mutation Met918 Thr in exon 16. In one MEN2B family beside this mutation the Tyr791 Phe was also found, which has not yet been reported. MEN2A was restricted to different mutations in exon 11 (codon 634). In FMTC and ‘sporadic’ MTC families the mutations in exons 10, 11, 13 and 14 were detected. The genotype/phenotype correlations are given. Genetic testing revealed germ-line mutations in 23 index patients, 24 family members and excluded them in 53 relatives.

Molecular Genetic Dissection of Mouse Unconventional Myosin-VA: Tail Region Mutations

Genetics ◽  
1998 ◽  
Vol 148 (4) ◽  
pp. 1963-1972 ◽  
Author(s):  
Jian-Dong Huang ◽  
Valerie Mermall ◽  
Marjorie C Strobel ◽  
Liane B Russell ◽  
Mark S Mooseker ◽  
...  
Keyword(s):  
Coat Color ◽  
Molecular Genetic ◽  
Genetic Dissection ◽  
Rt Pcr ◽  
Tail Region ◽  
Unconventional Myosin ◽  
Myosin Va ◽  
Cell Type Specific ◽  
Extensive Collection ◽  
Tail Function

AbstractWe used an RT-PCR-based sequencing approach to identify the mutations responsible for 17 viable dilute alleles, a mouse-coat-color locus encoding unconventional myosin-VA. Ten of the mutations mapped to the MyoVA tail and are reported here. These mutations represent the first extensive collection of tail mutations reported for any unconventional mammalian myosin. They identify sequences important for tail function and identify domains potentially involved in cargo binding and/or proper folding of the MyoVA tail. Our results also provide support for the notion that different myosin tail isoforms produced by alternative splicing encode important cell-type-specific functions.

scholarly journals Evaluation of Various Strategies to Generate NPM1mut-Specific T Cell Clones

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5718-5718 ◽  
Author(s):  
Elke Ruecker-Braun ◽  
Falk Heidenreich ◽  
Cornelia S Link ◽  
Maria Schmiedgen ◽  
Rebekka Wehner ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Checkpoint Inhibitors ◽  
Single Cells ◽  
Molecular Genetic ◽  
Specific Antigen ◽  
Positive Control ◽  
Low Frequencies ◽  
T Cell Clones ◽  
Cell Clones

Abstract Mutated nucleophosmin (NPM1) was identified as a promising leukemia-specific antigen for cytotoxic T lymphocytes (CTL). NPM1 is a multifunctional nucleocytoplasmic shuttling phosphoprotein. In AML patients with normal cytogenetics NPM1 mutations are the most frequent molecular genetic abnormalities, accounting for up to 60% of the patients. The peptide (AIQDLCLAV) derived from the mutated NPM1 (NPM1mut) has been described to elicit a CTL response restricted to HLA-A*02:01. We observed that NPM1mut multimer+ T cells were very rare in peripheral blood. The limitation of the multimer technology is the absence of a positive control; nevertheless it is an attractive tool to generate antigen positive T cell clones. The goal was to compare strategies for the generation of NPM1mut multimer+ T cell clones systematically. For this purpose we analyzed blood samples from two patients with AML after transplantation and six different healthy donors. We explored different strategies to isolate HLA-A*02:01 restricted NPM1mut multimer+ T single cells. The first strategy was to isolate multimer+ T cells directly from the blood without any supplements by single cell sorting. The second strategy was to sort multimer+ T cells which were previously CD8+ enriched supplementing the media either with or without IL-21. Published by Yongqing et al.IL-21 enhances the generation of human antigen-specific CD8+ T cells. A further strategy was to previously enrich CD14+ cells for the generation of autologous monocyte-derived dendritic cells (MoDCs). The co-cultivation of MoDCs loaded with the NPM1mut peptide and CD8+ cells were performed either with or without IL-21, as well. We expanded the last strategy by a second round of NPM1mut-specific stimulation. So far it was not possible to generate NPM1mut-specific T cell clones based on the advanced strategies and consistently there is no data published on NPM1mut multimer+ T cell clones. This fact raises the question why NPM1mut specific clones display such low frequencies. We want to point out that although we varied the strategies and we used eight different donors the isolation of NPM1mut-specific T cells restricted to HLA-A*02:01 apparently is challenging. Greater efforts, e.g. a larger number of donors or the use of immunological checkpoint inhibitors during cell culture are needed. Disclosures Thiede: AgenDix: Employment, Other: Ownership. Schetelig:Sanofi: Honoraria.

scholarly journals Mapping and identification of yellow seed coat color genes in Brassica juncea L.

2020 ◽  
Author(s):  
Zhen Huang ◽  
Yang Wang ◽  
Hong Lu ◽  
Xiang Liu ◽  
Lu Liu ◽  
...  
Keyword(s):  
Candidate Gene ◽  
Brassica Juncea ◽  
Seed Coat ◽  
Coat Color ◽  
Seed Color ◽  
Seed Coat Color ◽  
Flavonoid Pathway ◽  
Yellow Seed ◽  
Color Formation ◽  
Yellow Seed Coat

Abstract BackgroundYellow seed breeding is an effective method to improve the oil content in rapeseed. Yellow seed coat color formation is influenced by various factors, and no clear mechanisms are known. In this study, Bulked segregant RNA-Seq (BSR-Seq) of BC9 population of Wuqi mustard (yellow seed) and Wugong mustard (brown seed) was used to identity the candidate genes controlling the yellow seed color in Brassica juncea L.ResultsYellow seed coat color gene was mapped to chromosome A09, and differentially expressed genes (DEGs) between brown and yellow bulks enriched in the flavonoid pathway. A significant correlation between the expression of BjF3H and BjTT5 and the content of the seed coat color related indexes was identified. Two intron polymorphism (IP) markers linked to the target gene were developed around BjF3H. Therefore, BjF3H was considered as the candidate gene. The BjF3H coding sequences (CDS) of Wuqi mustard and Wugong mustard are 1071-1077bp, encoding protein of 356-358 amino acids. One amino acid change (254, F/V) was identified in the conserved domain. This mutation site was detected in four Brassica rapa (B. rapa) and six Brassica juncea (B. juncea) lines, but not in Brassica napus (B. napus).ConclusionsThe results indicated BjF3H is a candidate gene that related to yellow seed coat color formation in Brassica juncea and provided a comprehensive understanding of the yellow seed coat color mechanism.

scholarly journals Gastrointestinal stromal tumors (gists): Definition, clinical, histological, immunohistochemical and molecular genetic features and predictors of malignant potential and differential diagnosis

2002 ◽  
Vol 10 (4) ◽  
pp. 267-271 ◽  
Author(s):  
Vesna Zivkovic ◽  
Vuka Katic ◽  
Aleksandar Nagorni ◽  
Ljubinka Velickovic ◽  
Maja Milentijevic ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumors ◽  
Molecular Genetic ◽  
Malignant Potential ◽  
Gi Tract ◽  
Mesenchymal Tumors ◽  
Stromal Tumors ◽  
Cellular Origin ◽  
Genetic Features ◽  
Exon 11 ◽  
Malignant Gists

Gastrointestinal stromal tumors (GISTs) represent a distinct and the most important subset of mesenchymal tumors of the gastrointestinal (GI) tract GISTs occur throughout the GI tract but are usually located in the stomach and small intestine. The cellular origin, differentiation, nomenclature and prognosis of GISTs are controversial. Because GISTs, like the interstitial cells of Cajal, the GI pacemaker cells, express CD117 (c-kit protein), the origin of GISTs from the Cajal cells has recently been suggested. GISTs are also known for their wide variability in clinical behavior and for the difficulty to determine their malignant condition The most reproducible predictors of malignancy are mitotic count >1-5 per10 high-powered fields (HPF), size >5 cm, tumor necrosis, infiltration and metastasis to other sites. However, some tumors with mitotic activity <1/10 HPF may metastasize indicating some uncertainty in malignant potential of GISTs, especially those larger than 5 cm. Recently, mutations in c-kit gene (exon 11) preferentially occur in malignant GISTs and may be a clinically useful adjunct marker in evaluation of GISTs. In conclusion, the strong CD117 expression mostly defines primary GI mesenchymal tumors as GIST. Specific identification of GIST may become clinically important if therapies targeting the c-kit tyrosine kinase activation become available.

Ultrastructural studies of pigmented, depigmented and melanomatous skin in lipizzaner horses.

1978 ◽  
Vol 36 (2) ◽  
pp. 654-655
Author(s):  
W. Gebhart ◽  
G. Niebauer
Keyword(s):  
Coat Color ◽  
Energy Dispersive Spectrometer ◽  
Surgical Excision ◽  
Tumor Formation ◽  
Ultrastructural Studies ◽  
Biopsy Specimens ◽  
Suitable Animal Model ◽  
Computer Based ◽  
Melanotic Tumors ◽  
Dark Color

Lipizzaner horses - as well as some other graying breeds - undergo progressive depigmentation of their coat color and are regularily affected by melanotic tumors at older age. Although deeply pigmented at birth nearly all individuals loose their dark color at the age of 4 — 6 years and multiple melanotic tumors arise in skin. Unique melanomatosis is frequently present in 20 — 30 years old animal (Gebhart and Niebauer, 1977). These characteristics design the horses of the genetically well-defined Lipizzaner breed as a suitable animal model for studies on depigmentation and tumor formation processes. Histochemical and ultrastructural investigations were performed in order to elucidate the morphological substrates of pigmented and depigmented lesions.Biopsy specimens were obtained by surgical excision from pigmented and depigmented skin and from melanomas of 19 Lipizzaner horses. Immediately after excision the tissue was devided into several portions and processed for routine histology, DOPA-reaction and electron microscopy. Ultrastructural investigations were performed in a ZEISS EM 9S2 and a JEOL lOO C TEMSCAN electron microscope fitted with a computer based energy-dispersive spectrometer (LINK).

Truncation of Glycoprotein (GP) IIIa (▵ 616-762) Prevents Complex Formation With GPIIb: Novel Mutation in Exon 11 of GPIIIa Associated With Thrombasthenia

Blood ◽  
1998 ◽  
Vol 92 (12) ◽  
pp. 4712-4720 ◽  
Author(s):  
Milagros Ferrer ◽  
Jianming Tao ◽  
Gema Iruı́n ◽  
Matilde Sánchez-Ayuso ◽  
José González-Rodrı́guez ◽  
...  
Keyword(s):  
Complex Formation ◽  
Novel Mutation ◽  
Molecular Genetic ◽  
Coding Region ◽  
Chain Reaction ◽  
Molecular Genetic Study ◽  
Nonsense Mutations ◽  
Glanzmann Thrombasthenia ◽  
Polymerase Chain ◽  
Exon 11

This work reports the molecular genetic study of a patient who suffered from Glanzmann thrombasthenia (GT). Structural analysis of the glycoprotein (GP) IIb and GPIIIa genes showed the presence of a homozygous G1846→T transversion in exon 11 of GPIIIa that changes Glu616→Stop. Cytometric and immunochemical analysis indicated that platelet GPIIb-IIIa was absent in the proband but present at normal levels in the heterozygous relatives. The following observations indicate that this mutation is responsible for the thrombasthenic phenotype of the proband. (1) We failed to detect mutations other than [T1846]GPIIIa in the coding region of both GPIIb and GPIIIa genes. (2) The G1846→T mutation was observed in either parent and a brother of the proband, but none of 100 unrelated individuals carried this defect. (3) Pulse-chase and immunoprecipitation analysis of GPIIb-IIIa complexes in cells transiently cotransfected with cDNAs encoding normal GPIIb and [T1846]GPIIIa showed neither maturation of GPIIb nor complex formation and surface exposure of GPIIb-▵GPIIIa. These observations indicate that the sequence from Glu616 to Thr762 in GPIIIa is essential for heterodimerization with GPIIb. Polymerase chain reaction-based analysis demonstrated the presence of normal levels of full-length GPIIIa-mRNA in the proband and in heterozygous relatives. In addition, a shortened transcript, with a 324-nucleotide deletion, resulting from in-frame skipping of exons 10 and 11, was detectable upon reamplification of the DNA. Thus, unlike other nonsense mutations, [T1846]GPIIIa does not lead to abnormal processing or reduction in the number of transcripts with the termination codon.

scholarly journals Corrective recombination of mouse immunoglobulin kappa alleles in Abelson murine leukemia virus-transformed pre-B cells.

1990 ◽  
Vol 10 (2) ◽  
pp. 569-576 ◽  
Author(s):  
R M Feddersen ◽  
B G Van Ness
Keyword(s):  
Murine Leukemia Virus ◽  
Germ Line ◽  
Leukemia Virus ◽  
Full Spectrum ◽  
Immunoglobulin Kappa ◽  
Cell Clones ◽  
Mouse Immunoglobulin ◽  
Clonal Cell Lines ◽  
Abelson Murine Leukemia Virus ◽  
Murine Leukemia

Previous characterization of mouse immunoglobulin kappa gene rearrangement products cloned from murine plasmacytomas has indicated that two recombination events can take place on a single kappa allele (R. M. Feddersen and B. G. Van Ness, Proc. Natl. Acad. Sci. USA 82:4792-4797, 1985; M. A. Shapiro and M. Weigert, J. Immunol. 139:3834-3839, 1987). To determine whether multiple recombinations on a single kappa allele can contribute to the formation of productive V-J genes through corrective recombinations, we have examined several Abelson murine leukemia virus-transformed pre-B-cell clones which rearrange the kappa locus during cell culture. Clonal cell lines which had rearranged one kappa allele nonproductively while maintaining the other allele in the germ line configuration were grown, and secondary subclones, which subsequently expressed kappa protein, were isolated and examined for further kappa rearrangement. A full spectrum of rearrangement patterns was observed in this sequential cloning, including productive and nonproductive recombinations of the germ line allele and secondary recombinations of the nonproductive allele. The results show that corrective V-J recombinations, with displacement of the nonproductive kappa gene, occur with a significant frequency (6 of 17 kappa-producing subclones). Both deletion and maintenance of the primary (nonfunctional) V-J join, as a reciprocal product, were observed.

In utero manipulation of coat color formation by a monoclonal anti-c-kit antibody: two distinct waves of c-kit-dependency during melanocyte development.

1991 ◽  
Vol 10 (8) ◽  
pp. 2111-2118 ◽  
Author(s):  
S. Nishikawa ◽  
M. Kusakabe ◽  
K. Yoshinaga ◽  
M. Ogawa ◽  
S. Hayashi ◽  
...  
Keyword(s):  
Coat Color ◽  
In Utero ◽  
Color Formation

PHOTOMETRIC STUDIES ON THE DIAZO REACTION FOR SERUM BILIRUBIN

1952 ◽  
Vol 30 (6) ◽  
pp. 552-560
Author(s):  
F. D. White ◽  
Dorothea Duncan
Keyword(s):  
Sodium Salt ◽  
Calibration Curve ◽  
Serum Bilirubin ◽  
Alcohol Solution ◽  
Color Intensity ◽  
Color Formation ◽  
Color Development ◽  
Beer's Law ◽  
Beer’S Law

Photometric studies on the Malloy-Evelyn procedure for the determination of serum bilirubin have shown that the azobilirubin color intensity obtained when the diazo reagent acts for 30 min. upon a known amount of bilirubin added to serum in the form of the sodium salt is less than when the reaction takes place with the same amount of bilirubin in chloroform-alcohol solution. This suggests that the usual calibration curve prepared from bilirubin in chloroform-alcohol solution, when used as standard for serum bilirubin determinations, may give values which are about 10% less than the true bilirubin content of the serum. It has also been shown that with the 1 : 10 dilution of the Malloy-Evelyn procedure the azobilirubin from icteric sera does not obey Beer’s law beyond a serum bilirubin content of 15 mgm. per 100 ml. Evidence is submitted that the rate of azobilirubin color formation can be markedly accelerated by increasing the strength of the diazo reagent, and a new reagent is proposed by the use of which the time of color development can be reduced from 30 min. to 5 min.

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