Pi&lt;sup&gt;Winneytown&lt;/sup&gt;: New Alpha&lt;sub&gt;1&lt;/sub&gt;-Antitrypsin Allele in an American Negro Family

Hug, George; Chuck, Gail; McGill, Manley

doi:10.1159/000153307

Cited by 6 publications

(4 citation statements)

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“…Bioinformatics methods for such purpose fall into two groups: strategies that use sequence, structural data and physicochemical features, and methods that are based on network construction. The latter can provide the inherent characteristics of topological configuration of associated biological networks which is often disregarded by the former strategies 6 . In the present work, we used GPL570 which is a good platform to evaluate the expression level of lncRNAs in tumorigenesis 11 , 28 .…”

Section: Discussionmentioning

confidence: 99%

“…However, several recent studies have indicated significance of other genes and signaling pathways in determination of overall survival (OS) of patients 2 , 5 . Among the recently appreciated genes in this regard are long non-coding RNAs (lncRNAs) 6 . These transcripts are involved in the regulation of fundamental cell survival pathways and have functional interactions with proteins and other non-coding RNAs that participate in the pathogenesis of breast cancer 7 .…”

Section: Introductionmentioning

confidence: 99%

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An in-silico method leads to recognition of hub genes and crucial pathways in survival of patients with breast cancer

Dashti

Taheri

Ghafouri‐Fard

2020

Sci Rep

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Breast cancer is a highly heterogeneous disorder characterized by dysregulation of expression of numerous genes and cascades. In the current study, we aim to use a system biology strategy to identify key genes and signaling pathways in breast cancer. We have retrieved data of two microarray datasets (GSE65194 and GSE45827) from the NCBI Gene Expression Omnibus database. R package was used for identification of differentially expressed genes (DEGs), assessment of gene ontology and pathway enrichment evaluation. The DEGs were integrated to construct a protein–protein interaction network. Next, hub genes were recognized using the Cytoscape software and lncRNA–mRNA co-expression analysis was performed to evaluate the potential roles of lncRNAs. Finally, the clinical importance of the obtained genes was assessed using Kaplan–Meier survival analysis. In the present study, 887 DEGs including 730 upregulated and 157 downregulated DEGs were detected between breast cancer and normal samples. By combining the results of functional analysis, MCODE, CytoNCA and CytoHubba 2 hub genes including MAD2L1 and CCNB1 were selected. We also identified 12 lncRNAs with significant correlation with MAD2L1 and CCNB1 genes. According to The Kaplan–Meier plotter database MAD2L1, CCNA2, RAD51-AS1 and LINC01089 have the most prediction potential among all candidate hub genes. Our study offers a framework for recognition of mRNA–lncRNA network in breast cancer and detection of important pathways that could be used as therapeutic targets in this kind of cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An in-silico method leads to recognition of hub genes and crucial pathways in survival of patients with breast cancer

Dashti

Taheri

Ghafouri‐Fard

2020

Sci Rep

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“…In addition, another scarce variant PIPclifton was detected in some Berber groups. This variant, which had been reported in a North American population originated from sub-Saharan Africa (Hug et al, 1981), is often associated with immunoglobulin GM and Cγ haplotypes frequent in subSaharan African populations. Thus, it seems to be typical to these populations (Chaabani et al, 1986) and shows the presence of sub-Saharan African traces in the gene pool of North African populations.…”

Section: Aat Gene Variants and Their Use In Anthropological Investigamentioning

confidence: 74%

Origins and spreads of Alpha 1 antitrypsin variants in world human populations: a synthetic review

Denden¹,

Chibani²,

Khelil³

2012

Int.J.Mod.Anthrop

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-Human Alpha 1 antitrypsin (AAT) or protease inhibitor (PI) is a highly polymorphic glycoprotein. In this review report distributions of all detected AAT allelic variants in different world populations are collected showing their anthropological usefulness. Some variants are related to AAT deficiency (AATD) which is one of the most common genetic disorders worldwide. Data on PIS and PIZ, most common AATD mutations, and their worldwide distribution are also reported. Studies on DNA haplotypes were particularly useful for the estimations of PIS and PIZ mutations ages and worldwide spread. According to these data, it seems very likely that the PIZ mutation occurred in Sweden and was spread into the rest of the European continent via the Baltic countries. However, in a second hypothesis authors suggested multiple origins of this mutation. The highest frequencies of the PIS mutation in the Iberian Peninsula were linked to an early occurrence of the mutation in this region, before its spread throughout the Europeans countries and the Iberian Peninsula settlements and trading networks. However, the PIS allele may have been further dispersed by multiple occurrences of the mutation. This multiple origins of AAT variants could explain the higher frequencies and haplotype diversities in PIM1Val and PIM2 alleles, rather than their older base alleles (PIM1Ala and PIM3, respectively). Data on rare variants, which seem not to be so rare in some populations, are still lacking. The only reliable data, on the age of a rare AATD variant, was given on an autochthonous allele (NullOurém).

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“…46,50,52,53 Furthermore, the significant cost of augmentation therapy (total healthcare cost range from $36,471 to $46,114), its short-term effect, and the lack of noninvasive therapeutic options for AATD patients Approximately 30 variants of alpha-1-antitrypsin had been described and named according to the electrophoretic mobility in 1981. 25 Seventy-five alleles have been identified at the protein and gene level, including 10 normal AAT alleles. 26 The Ml (Val213) variant is the most common (44-49%).…”

Section: Conventional Therapies: Why They Are Insufficientmentioning

confidence: 99%

Challenges and Prospects for Alpha-1 Antitrypsin Deficiency Gene Therapy

et al. 2015

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Alpha-1 antitrypsin (AAT) is a protease inhibitor belonging to the serpin family. A number of identified mutations in the SERPINA1 gene encoding this protein result in alpha-1 antitrypsin deficiency (AATD). A decrease in AAT serum concentration or reduced biological activity causes considerable risk of chronic respiratory and liver disorders. As a monogenic disease, AATD appears to be an attractive target for gene therapy, particularly for patients with pulmonary dysfunction, where augmentation of functional AAT levels in plasma might slow down respiratory disease development. The short AAT coding sequence and its activity in the extracellular matrix would enable an increase in systemic serum AAT production by cellular secretion. In vitro and in vivo experimental AAT gene transfer with gamma-retroviral, lentiviral, adenoviral, and adeno-associated viral (AAV) vectors has resulted in enhanced AAT serum levels and a promising safety profile. Human clinical trials using intramuscular viral transfer with AAV1 and AAV2 vectors of the AAT gene demonstrated its safety, but did not achieve a protective level of AAT >11 μM in serum. This review provides an in-depth critical analysis of current progress in AATD gene therapy based on viral gene transfer. The factors affecting transgene expression levels, such as site of administration, dose and type of vector, and activity of the immune system, are discussed further as crucial variables for optimizing the clinical effectiveness of gene therapy in AATD subjects.

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Pi<sup>Winneytown</sup>: New Alpha<sub>1</sub>-Antitrypsin Allele in an American Negro Family

Abstract: Alpha₁-antitrypsin allele Pi^Winneytown is traced in the family of a black man whose serum exhibits the new phenotype Wfinneytown. Affected individuals show no signs of disease. This is the fourth α₁-antitrypsin variant discovered in the local negro population.

Cited by 6 publications

References 4 publications

An in-silico method leads to recognition of hub genes and crucial pathways in survival of patients with breast cancer

An in-silico method leads to recognition of hub genes and crucial pathways in survival of patients with breast cancer

Origins and spreads of Alpha 1 antitrypsin variants in world human populations: a synthetic review

Challenges and Prospects for Alpha-1 Antitrypsin Deficiency Gene Therapy

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Pi<sup>Winneytown</sup>: New Alpha<sub>1</sub>-Antitrypsin Allele in an American Negro Family

Abstract: Alpha1-antitrypsin allele PiWinneytown is traced in the family of a black man whose serum exhibits the new phenotype Wfinneytown. Affected individuals show no signs of disease. This is the fourth α1-antitrypsin variant discovered in the local negro population.

Cited by 6 publications

References 4 publications

An in-silico method leads to recognition of hub genes and crucial pathways in survival of patients with breast cancer

An in-silico method leads to recognition of hub genes and crucial pathways in survival of patients with breast cancer

Origins and spreads of Alpha 1 antitrypsin variants in world human populations: a synthetic review

Challenges and Prospects for Alpha-1 Antitrypsin Deficiency Gene Therapy

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Product

Resources

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Abstract: Alpha₁-antitrypsin allele Pi^Winneytown is traced in the family of a black man whose serum exhibits the new phenotype Wfinneytown. Affected individuals show no signs of disease. This is the fourth α₁-antitrypsin variant discovered in the local negro population.